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Review Front Oncol
. 2020 May 19;10:851. doi: 10.3389/fonc.2020.00851. eCollection 2020.
Metabolic Traits in Cutaneous Melanoma
Monica Neagu 1 2 3
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PMID: 32509589 PMCID: PMC7248353 DOI: 10.3389/fonc.2020.00851
Abstract
Tumor microenvironment is a network of complex cellular and molecular systems where cells will gain specific phenotypes and specific functions that would drive tumorigenesis. In skin cancers, tumor microenvironment is characterized by tumor infiltrating immune cells that sustain immune suppression, mainly lymphocytes. Melanoma cellular heterogeneity can be described on genetic, proteomic, transcriptomic and metabolomic levels. Melanoma cells display a metabolic reprogramming triggered by both genetic alterations and adaptation to a microenvironment that lacks nutrients and oxygen supply. Tumor cells present clear metabolic adaptations and identifying deregulated glycolysis pathway could offer new therapy targets. Moreover, the immune cells (T lymphocytes, macrophages, NK cells, neutrophils and so on) that infiltrate melanoma tumors have metabolic particularities that, upon interaction within tumor microenvironment, would favor tumorigenesis. Analyzing both tumor cell metabolism and the metabolic outline of immune cells can offer innovative insights in new therapy targets and cancer therapeutical approaches. In addition to already approved immune- and targeted therapy in melanoma, approaching metabolic check-points could improve therapy efficacy and hinder resistance to therapy.

Keywords: immune cells; melanoma; metabolism; therapy; tumor microenvironment.

Copyright © 2020 Neagu.

112 references2 figures
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Review Front Oncol
. 2020 May 19;10:779. doi: 10.3389/fonc.2020.00779. eCollection 2020.
Electrolyte Disorders Induced by Antineoplastic Drugs
Ignazio Verzicco 1, Giuseppe Regolisti 2, Federico Quaini 3, Pietro Bocchi 1, Irene Brusasco 1, Massimiliano Ferrari 1, Giovanni Passeri 4, Valentina Cannone 1, Pietro Coghi 1, Enrico Fiaccadori 2, Alessandro Vignali 1, Riccardo Volpi 1 4, Aderville Cabassi 1
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PMID: 32509580 PMCID: PMC7248368 DOI: 10.3389/fonc.2020.00779
Abstract
The use of antineoplastic drugs has a central role in treatment of patients affected by cancer but is often associated with numerous electrolyte derangements which, in many cases, could represent life-threatening conditions. In fact, while several anti-cancer agents can interfere with kidney function leading to acute kidney injury, proteinuria, and hypertension, in many cases alterations of electrolyte tubular handling and water balance occur. This review summarizes the mechanisms underlying the disturbances of sodium, potassium, magnesium, calcium, and phosphate metabolism during anti-cancer treatment. Platinum compounds are associated with sodium, potassium, and magnesium derangements while alkylating agents and Vinca alkaloids with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Novel anti-neoplastic agents, such as targeted therapies (monoclonal antibodies, tyrosine kinase inhibitors, immunomodulators, mammalian target of rapamycin), can induce SIADH-related hyponatremia and, less frequently, urinary sodium loss. The blockade of epidermal growth factor receptor (EGFR) by anti-EGFR antibodies can result in clinically significant magnesium and potassium losses. Finally, the tumor lysis syndrome is associated with hyperphosphatemia, hypocalcemia and hyperkalemia, all of which represent serious complications of chemotherapy. Thus, clinicians should be aware of these side effects of antineoplastic drugs, in order to set out preventive measures and start appropriate treatments.

Keywords: antidiuretic hormone (ADH); antineoplastic drug exposure; electrolytes abnormalities; renal tubulopathies; tumor lysis syndrome.

Copyright © 2020 Verzicco, Regolisti, Quaini, Bocchi, Brusasco, Ferrari, Passeri, Cannone, Coghi, Fiaccadori, Vignali, Volpi and Cabassi.

173 references
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Review Front Oncol
. 2020 May 20;10:792. doi: 10.3389/fonc.2020.00792. eCollection 2020.
Metabolic Reprogramming and Epithelial-Mesenchymal Plasticity: Opportunities and Challenges for Cancer Therapy
Nai-Yun Sun 1 2, Muh-Hwa Yang 1 2 3
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PMID: 32509584 PMCID: PMC7252305 DOI: 10.3389/fonc.2020.00792
Abstract
Metabolic reprogramming and epithelial-mesenchymal plasticity are both hallmarks of the adaptation of cancer cells for tumor growth and progression. For metabolic changes, cancer cells alter metabolism by utilizing glucose, lipids, and amino acids to meet the requirement of rapid proliferation and to endure stressful environments. Dynamic changes between the epithelial and mesenchymal phenotypes through epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are critical steps for cancer invasion and metastatic colonization. Compared to the extensively studied metabolic reprogramming in tumorigenesis, the metabolic changes in metastasis are relatively unclear. Here, we review metabolic reprogramming, epithelial-mesenchymal plasticity, and their mutual influences on tumor cells. We also review the developing treatments for targeting cancer metabolism and the impact of metabolic targeting on EMT. In summary, understanding the metabolic adaption and phenotypic plasticity will be mandatory for developing new strategies to target metastatic and refractory cancers that are intractable to current treatments.

Keywords: aerobic glycolysis; cancer metabolism; drug resistance; epithelial-mesenchymal plasticity; metastasis.

Copyright © 2020 Sun and Yang.

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Review Front Oncol
. 2020 May 19;10:660. doi: 10.3389/fonc.2020.00660. eCollection 2020.
Adenylate Kinase and Metabolic Signaling in Cancer Cells
Aleksandr Klepinin 1, Song Zhang 2, Ljudmila Klepinina 1, Egle Rebane-Klemm 1, Andre Terzic 2, Tuuli Kaambre 1, Petras Dzeja 2
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PMID: 32509571 PMCID: PMC7248387 DOI: 10.3389/fonc.2020.00660
Abstract
A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ AMP→ AMPK signaling controlling cell cycle and proliferation, and ATP energy transfer from mitochondria to distribute energy among cellular processes. The significance of AK isoform network in the regulation of a variety of cellular processes, which include cell differentiation and motility, is rapidly growing. Adenylate kinase 2 (AK2) isoform, localized in intermembrane and intra-cristae space, is vital for mitochondria nucleotide exchange and ATP export. AK2 deficiency disrupts cell energetics, causes severe human diseases, and is embryonically lethal in mice, signifying the importance of catalyzed phosphotransfer in cellular energetics. Suppression of AK phosphotransfer and AMP generation in cancer cells and consequently signaling through AMPK could be an important factor in the initiation of cancerous transformation, unleashing uncontrolled cell cycle and growth. Evidence also builds up that shift in AK isoforms is used later by cancer cells for rewiring energy metabolism to support their high proliferation activity and tumor progression. As cell motility is an energy-consuming process, positioning of AK isoforms to increased energy consumption sites could be an essential factor to incline cancer cells to metastases. In this review, we summarize recent advances in studies of the significance of AK isoforms involved in cancer cell metabolism, metabolic signaling, metastatic potential, and a therapeutic target.

Keywords: adenylate kinase; cancer; energy metabolism; mitochondria; phosphotransfer.

Copyright © 2020 Klepinin, Zhang, Klepinina, Rebane-Klemm, Terzic, Kaambre and Dzeja.

107 references1 figure
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Review Front Oncol
. 2020 May 20;10:837. doi: 10.3389/fonc.2020.00837. eCollection 2020.
Deep Penetrating Nevus and Borderline-Deep Penetrating Nevus: A Literature Review
Ioana Cosgarea 1 2, Klaus G Griewank 3 4, Loredana Ungureanu 5, Arturo Tamayo 6, Timo Siepmann 2 7
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PMID: 32509588 PMCID: PMC7251176 DOI: 10.3389/fonc.2020.00837
Abstract
Deep penetrating nevi (DPN) are rare melanocytic nevi, which can exhibit atypical histological features hampering the differentiation from malignant melanoma. DPN are considered benign melanocytic lesions, but rare spread to lymph nodes and unfavorable clinical outcomes associated with borderline/atypical DPN (B-DPN) has been reported. Since no guidelines are available for DPN and B-DPN, we aimed to review the literature on DPN and B-DPN to assess the management and prognosis. We screened 3,513 references from EMBASE, Scopus and Medline databases, and included 15 studies with a total of 355 DPN patients and 48 B-DPN patients. Therapeutic interventions ranged from simple excision to wide excisions and sentinel lymph node biopsy (SLNB), with block lymph node dissection in some positive SLNB cases. Follow-up periods ranged from 3 months to 23 years during which a total of five recurrences, two in DPN and three in B-DPN group, and three metastases, in B-DPN group, were reported. While some of the included studies comprised clinical and histopathological correlation, few included genetic assessment. The present review highlights the need for prospective cohort studies applying composite measures to identify effective regimens of diagnostic workup and treatment in DPN and B-DPN.

Keywords: DPN; DPN treatment; borderline/atypical deep penetrating nevus; borderline/atypical deep penetrating nevus treatment; deep penetrating nevus.

Copyright © 2020 Cosgarea, Griewank, Ungureanu, Tamayo and Siepmann.

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Review Front Oncol
. 2020 May 20;10:741. doi: 10.3389/fonc.2020.00741. eCollection 2020.
Targeted Therapies and Biomarkers in Small Cell Lung Cancer
Hirokazu Taniguchi 1 2, Triparna Sen 1 3, Charles M Rudin 1 3
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PMID: 32509576 PMCID: PMC7251180 DOI: 10.3389/fonc.2020.00741
Abstract
Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid growth, early metastasis, and acquired therapeutic resistance. A majority of patients with SCLC have extensive-stage (ES) disease, defined as the presence of metastatic disease outside the hemithorax at first diagnosis. SCLC has been considered "a graveyard for drug development," with chemotherapy remaining the standard treatment for first- and second-line management until quite recently. In contrast to NSCLC, identifying therapeutic targets in SCLC has been challenging, partly because driver mutations are primarily loss of function, involving the tumor suppressor genes RB1 and TP53 or currently untargetable (e.g., amplification of MYC family members). Recent gene expression profiling of SCLC cells lines, patient samples and representative murine models, have led to a proposed delineation of four major subtypes for SCLC distinguished by differential expression of four key transcriptional regulators (ASCL1, NEUROD1, POU2F3, and YAP1). Our understanding of the biology of SCLC has indeed significantly improved recently due to the continued efforts of the dedicated investigators in this field, but the therapeutic options remain dismal. While recent results from immunotherapy trials are encouraging, most patients demonstrate either primary or rapid acquired resistance to current regimens, highlighting the clear need to improve the effectiveness and expand the scope of current therapeutic strategies. In this opinion article, we will discuss recent developments in the treatment of SCLC, focused on current understanding of the signaling pathways, the role of immunotherapy and targeted therapy, and emerging biomarkers of response to therapy in SCLC.

Keywords: DNA damage repair pathway; SCLC; biomarker; immune therapy; targeted therapy.

Copyright © 2020 Taniguchi, Sen and Rudin.

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Review Front Oncol
. 2020 May 20;10:787. doi: 10.3389/fonc.2020.00787. eCollection 2020.
Biomechanical Contributions to Macrophage Activation in the Tumor Microenvironment
Erica J Hoffmann 1, Suzanne M Ponik 1 2
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PMID: 32509583 PMCID: PMC7251173 DOI: 10.3389/fonc.2020.00787
Abstract
Alterations in extracellular matrix composition and organization are known to promote tumor growth and metastatic progression in breast cancer through interactions with tumor cells as well as stromal cell populations. Macrophages display a spectrum of behaviors from tumor-suppressive to tumor-promoting, and their function is spatially and temporally dependent upon integrated signals from the tumor microenvironment including, but not limited to, cytokines, metabolites, and hypoxia. Through years of investigation, the specific biochemical cues that recruit and activate tumor-promoting macrophage functions within the tumor microenvironment are becoming clear. In contrast, the impact of biomechanical stimuli on macrophage activation has been largely underappreciated, however there is a growing body of evidence that physical cues from the extracellular matrix can influence macrophage migration and behavior. While the complex, heterogeneous nature of the extracellular matrix and the transient nature of macrophage activation make studying macrophages in their native tumor microenvironment challenging, this review highlights the importance of investigating how the extracellular matrix directly and indirectly impacts tumor-associated macrophage activation. Additionally, recent advances in investigating macrophages in the tumor microenvironment and future directions regarding mechano-immunomodulation in cancer will also be discussed.

Keywords: breast cancer; collagen; extracellular matrix; integrins; macrophage activation; mechanosensing; tumor microenvironment.

Copyright © 2020 Hoffmann and Ponik.

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Front Oncol
. 2020 May 20;10:671. doi: 10.3389/fonc.2020.00671. eCollection 2020.
Clinical Significances of Positive Postoperative Serum CEA and Post-preoperative CEA Increment in Stage II and III Colorectal Cancer: A Multicenter Retrospective Study
Weiqiang You 1, Li Yan 1, Zerong Cai 2, Lei Xie 3, Nengquan Sheng 1, Guiyu Wang 3, Xiaojian Wu 2, Zhigang Wang 1
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PMID: 32509572 PMCID: PMC7251078 DOI: 10.3389/fonc.2020.00671
Abstract
Background: Carcinoembryonic antigen (CEA) is the most common serum tumor marker in colorectal cancer (CRC). Nevertheless, few previous studies demonstrated the impacts of postoperative CEA and post-preoperative CEA increment on prognosis of CRC. Methods: Patients with stage II and III CRC were included from January 2009 to December 2015. All clinical and follow-up data were collected. Patients were divided into four different groups according to the levels of postoperative serum CEA and post-preoperative CEA trends. Chi-square test was used to analyze the relationship between clinical variables and categorized postoperative CEA and CEA increment. Cox proportional hazard regression was used for univariate and multivariable analyses. The log-rank test was performed to compare PFS and OS among groups. Results: Patients, 1,008, who underwent radical surgery, were enrolled. Our results showed that positive postoperative CEA and CEA increment were related to clinical stage, T stage, N stage, tumor differentiation, and lymphatic invasion (p < 0.05). Univariate and multivariable analysis results suggested that positive postoperative CEA and CEA increment were independent prognostic factors for PFS (HR = 3.149, 95% CI, 2.426-4.088, p = 0.000 for postoperative CEA; HR = 2.708, 95% CI, 2.106-3.482, p = 0.000 for CEA increment) and OS (HR = 3.414, 95% CI, 2.549-4.574, p = 0.000 for postoperative CEA; HR = 2.373, 95% CI, 1.783-3.157, p = 0.000 for CEA increment). The survival analyses revealed positive postoperative CEA, and CEA increment predicted worse prognosis. Furthermore, our results indicated that the 3- and 5-year PFS rates were 86.6 and 78.4% in group A, but decreased to 25.3 and 7.2% in group D (p < 0.001). Similarly, the 3- and 5-year OS rates for group A were 92.5 and 83.9%, much higher than group D (p < 0.001). In other words, patients with both postoperative CEA elevation and CEA increment had the worst prognosis. Conclusions: Positive postoperative CEA and CEA increment were independent prognostic factors for stage II and III CRC. Additionally, postoperative CEA and CEA increment had significant impacts on PFS and OS of CRC.

Keywords: carcinoembryonic antigen; colorectal cancer; prognosis; stage II; stage III.

Copyright © 2020 You, Yan, Cai, Xie, Sheng, Wang, Wu and Wang.

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9
Front Oncol
. 2020 May 19;10:725. doi: 10.3389/fonc.2020.00725. eCollection 2020.
CDCA2 Inhibits Apoptosis and Promotes Cell Proliferation in Prostate Cancer and Is Directly Regulated by HIF-1α Pathway
Yixiang Zhang 1, Yingduan Cheng 2, Zhaoxia Zhang 3, Zhongyuan Bai 1, Hongtao Jin 4, Xiaojing Guo 4, Xiaoyan Huang 5, Meiqi Li 5, Maolin Wang 5, Xing-Sheng Shu 5, Yeqing Yuan 1, Ying Ying 5
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PMID: 32509575 PMCID: PMC7248370 DOI: 10.3389/fonc.2020.00725
Abstract
Prostate cancer (PCa) is a major serious malignant tumor and is commonly diagnosed in older men. Identification of novel cancer-related genes in PCa is important for understanding its tumorigenesis mechanism and developing new therapies against PCa. Here, we used RNA sequencing to identify the specific genes, which are upregulated in PCa cell lines and tissues. The cell division cycle associated protein (CDCA) family, which plays a critical role in cell division and proliferation, is upregulated in the PCa cell lines of our RNA-Sequencing data. Moreover, we found that CDCA2 is overexpressed, and its protein level positively correlates with its histological grade, clinical stage, and Gleason Score. CDCA2 was further found to be upregulated and correlated with poor prognosis and patient survival in multiple cancer types in The Cancer Genome Atlas (TCGA) dataset. The functional study suggests that inhibition of CDCA2 will lead to apoptosis and lower proliferation in vitro. Silencing of CDCA2 also repressed tumor growth in vivo. Loss of CDCA2 affects several oncogenic pathways, including MAPK signaling. In addition, we further demonstrated that CDCA2 was induced in hypoxia and directly regulated by the HIF-1α/Smad3 complex. Thus, our data indicate that CDCA2 could act as an oncogene and is regulated by hypoxia and the HIF-1αpathway. CDCA2 may be a useful prognostic biomarker and potential therapeutic target for PCa.

Keywords: CDCA2; HIF-1a; apoptosis; proliferation; prostate cancer.

Copyright © 2020 Zhang, Cheng, Zhang, Bai, Jin, Guo, Huang, Li, Wang, Shu, Yuan and Ying.

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Front Oncol
. 2020 May 19;10:715. doi: 10.3389/fonc.2020.00715. eCollection 2020.
Patterns of Extrathoracic Metastases in Different Histological Types of Lung Cancer
Xuan Wang 1, Zheng Wang 2, Junjie Pan 3, Zhou-Yi Lu 1, Dong Xu 1, Hui-Jun Zhang 1, Shao-Hua Wang 1, Da-Yu Huang 1, Xiao-Feng Chen 1
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PMID: 32509574 PMCID: PMC7248315 DOI: 10.3389/fonc.2020.00715
Abstract
Lung cancer is the leading cause of cancer-related deaths mainly attributable to metastasis, especially extrathoracic metastasis. This large-cohort research is aimed to explore metastatic profiles in different histological types of lung cancer, as well as to assess clinicopathological and survival significance of diverse metastatic lesions. Lung cancer cases were extracted and enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. χ2-tests were conducted to make comparisons of metastatic distribution among different histological types and odds ratios were calculated to analyze co-occurrence relationships between different metastatic lesions. Kaplan-Meier methods were performed to analyze survival outcomes according to different metastatic sites and Cox regression models were conducted to identify independent prognostic factors. In total, we included 159,241 lung cancer cases with detailed metastatic status and complete follow-up information. In order to understand their metastatic patterns, we elucidated the following points in this research: (1) Comparing the frequencies of different metastatic lesions in different histological types. The frequency of bone metastasis was highest in adenocarcinoma, squamous cell carcinoma, LCLC and NSCLC/NOS, while liver was the most common metastatic site in SCLC. (2) Elaborating the tendency of combined metastases. Bi-site metastases occurred more common than tri-site and tetra-site metastases. And several metastatic sites, such as bone and liver, intended to co-metastasize preferentially. (3) Clarifying the prognostic significance of single-site and bi-site metastases. All single-site metastases were independent prognostic factors and co-metastases ended up with even worse survival outcomes. Thus, our findings would be beneficial for research design and clinical practice.

Keywords: histological type; lung cancer; metastasis; pattern; survival.

Copyright © 2020 Wang, Wang, Pan, Lu, Xu, Zhang, Wang, Huang and Chen.

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Front Oncol
. 2020 May 19;10:534. doi: 10.3389/fonc.2020.00534. eCollection 2020.
Accurate Preoperative Distinction of Intracranial Hemangiopericytoma From Meningioma Using a Multihabitat and Multisequence-Based Radiomics Diagnostic Technique
Jingwei Wei 1 2 3, Lianwang Li 4, Yuqi Han 1 2 3, Dongsheng Gu 1 2 3, Qian Chen 5, Junmei Wang 6, Runting Li 4, Jiong Zhan 5, Jie Tian 1 2 3 7 8, Dabiao Zhou 4 9
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PMID: 32509567 PMCID: PMC7248296 DOI: 10.3389/fonc.2020.00534
Abstract
Background: Intracranial hemangiopericytoma (IHPC) and meningioma are both meningeal neoplasms, but they have extremely different malignancy and outcomes. Because of their similar radiological characteristics, they are difficult to distinguish prior to surgery, leading to a high rate of misdiagnosis. Methods: We enrolled 292 patients (IHPC, 155; meningiomas, 137) with complete clinic-radiological and histopathological data, from a 10-year database established at Tiantan hospital. Radiomics analysis of tumor and peritumoral edema was performed on multisequence magnetic resonance images, and a fusion radiomics signature was generated using a machine-learning strategy. By combining clinic-radiological data with the fusion radiomics signature, we developed an integrated diagnostic approach that we named the IHPC and Meningioma Diagnostic Tool (HMDT). Results: The HMDT displayed remarkable diagnostic ability, with areas under the curve (AUCs) of 0.985 and 0.917 in the training and validation cohorts, respectively. The calibration curve showed excellent agreement between the diagnosis predicted by HMDT and the histological outcome, with p-values of 0.801 and 0.622 for the training and the validation cohorts, respectively. Cross-validation showed no statistical difference across three divisions of the cohort, with average AUCs of 0.980 and 0.941 for the training and validation cohorts, respectively. Stratification analysis showed consistent performance of the HMDT in distinguishing IHPC from highly misdiagnosed subgroups of grade I meningioma and angiomatous meningioma (AM) with AUCs of 0.913 and 0.914 in the validation cohorts for the two subgroups. Conclusions: By integrating clinic-radiological information with radiomics signature, the proposed HMDT could assist in preoperative diagnosis to distinguish IHPC from meningioma, providing the basis for strategic decisions regarding surgery.

Keywords: diagnosis; intracranial hemangiopericytoma; magnetic resonance imaging; meningioma; radiomics.

Copyright © 2020 Wei, Li, Han, Gu, Chen, Wang, Li, Zhan, Tian and Zhou.

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Front Oncol
. 2020 May 19;10:804. doi: 10.3389/fonc.2020.00804. eCollection 2020.
Integration of Transcriptome and Metabolome Provides Unique Insights to Pathways Associated With Obese Breast Cancer Patients
Mohammed A Hassan 1 2, Kaltoom Al-Sakkaf 3, Mohammed Razeeth Shait Mohammed 1, Ashraf Dallol 3 4, Jaudah Al-Maghrabi 5, Alia Aldahlawi 6 7, Sawsan Ashoor 8, Mabrouka Maamra 9, Jiannis Ragoussis 10, Wei Wu 11, Mohammad Imran Khan 1 12, Abdulrahman L Al-Malki 1 12, Hani Choudhry 1 12
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PMID: 32509585 PMCID: PMC7248369 DOI: 10.3389/fonc.2020.00804
Abstract
Information regarding transcriptome and metabolome has significantly contributed to identifying potential therapeutic targets for the management of a variety of cancers. Obesity has profound effects on both cancer cell transcriptome and metabolome that can affect the outcome of cancer therapy. The information regarding the potential effects of obesity on breast cancer (BC) transcriptome, metabolome, and its integration to identify novel pathways related to disease progression are still elusive. We assessed the whole blood transcriptome and serum metabolome, as circulating metabolites, of obese BC patients compared them with non-obese BC patients. In these patients' samples, 186 significant differentially expressed genes (DEGs) were identified, comprising 156 upregulated and 30 downregulated. The expressions of these gene were confirmed by qRT-PCR. Furthermore, 96 deregulated metabolites were identified as untargeted metabolomics in the same group of patients. These detected DEGs and deregulated metabolites enriched in many cellular pathways. Further investigation, by integration analysis between transcriptomics and metabolomics data at the pathway levels, revealed seven unique enriched pathways in obese BC patients when compared with non-obese BC patients, which may provide resistance for BC cells to dodge the circulating immune cells in the blood. In conclusion, this study provides information on the unique pathways altered at transcriptome and metabolome levels in obese BC patients that could provide an important tool for researchers and contribute further to knowledge on the molecular interaction between obesity and BC. Further studies are needed to confirm this and to elucidate the exact underlying mechanism for the effects of obesity on the BC initiation or/and progression.

Keywords: OLFM4; breast cancer; integration metabolism; metabolomics; obesity; transcriptomics; whole blood.

Copyright © 2020 Hassan, Al-Sakkaf, Shait Mohammed, Dallol, Al-Maghrabi, Aldahlawi, Ashoor, Maamra, Ragoussis, Wu, Khan, Al-Malki and Choudhry.

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Front Oncol
. 2020 May 19;10:825. doi: 10.3389/fonc.2020.00825. eCollection 2020.
Response Evaluation of Choroidal Melanoma After Brachytherapy Using Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI): Preliminary Findings
Flávia B C S N Bitencourt 1, Almir G V Bitencourt 2, Martha M M Chojniak 3, Juliana O Souza 2, Douglas G Castro 4, Antônio Cassio A Pellizzon 4, Rubens Chojniak 2
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PMID: 32509587 PMCID: PMC7248391 DOI: 10.3389/fonc.2020.00825
Abstract
Purpose: To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of therapeutic response in patients with choroidal melanoma treated with brachytherapy. Materials and Methods: We performed a prospective, unicentric study which included patients with choroidal melanoma and indication for brachytherapy. Three DW-MRI examinations were proposed for each patient, one before and two after treatment. The apparent diffusion coefficient (ADC) value was calculated on DW-MRI and compared with local tumor control assessed by ophthalmologic follow-up. Results: From 07/2018 to 06/2019, 19 patients were recruited, 13 of whom underwent follow-up examinations. Patients' ages ranged from 24 to 78 years and 52.9% were male. At the ocular ultrasound, the mean tumor thickness and diameter were 6.3 and 11.5 mm, respectively. Two patients (15.4%) showed signs of tumor progression during follow-up (7 and 9 months after treatment). There was no statistically significant difference in tumor size between MR before and after treatment, however, there was a significant reduction in mean ADC in patients with progression (p = 0.02). Conclusion: DW-MRI is a promising method for monitoring patients with choroidal melanoma; reduction in the mean ADC values between pre-treatment MRI and the first post-treatment MRI may be related to the lack of response to brachytherapy and increased risk of disease progression.

Keywords: brachytherapy; diffusion magnetic resonance imaging; eye neoplasms; melanoma; response evaluation criteria in solid tumors.

Copyright © 2020 Bitencourt, Bitencourt, Chojniak, Souza, Castro, Pellizzon and Chojniak.

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Front Oncol
. 2020 May 20;10:785. doi: 10.3389/fonc.2020.00785. eCollection 2020.
Genetic Variant in Long Non-Coding RNA H19 Modulates Its Expression and Predicts Renal Cell Carcinoma Susceptibility and Mortality
Qiang Cao 1, Pengchao Li 1, Pu Cao 2, Jian Qian 1, Mulong Du 3, Li Li 4, Meilin Wang 3, Chao Qin 1, Pengfei Shao 1, Zhengdong Zhang 3, Qiang Lu 1, Zengjun Wang 1
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PMID: 32509581 PMCID: PMC7251175 DOI: 10.3389/fonc.2020.00785
Abstract
The long non-coding RNA (lncRNA) H19 has been demonstrated to play a crucial role in carcinogenesis, including renal cell carcinoma (RCC). However, the impact of genetic variations in H19 gene on RCC has not been investigated before. In the present study, we sought to evaluate whether genetic polymorphisms in H19 are related to the susceptibility and mortality of RCC. We genotyped four widely studied polymorphisms in H19 and assessed their relationship with susceptibility and prognosis of RCC in a case-control study compromising 1,027 cases and 1,094 controls. The functionality of the important polymorphism was further investigated by real-time polymerase chain reaction and luciferase reporter assay. We found that H19 rs2839698 was significantly associated with risk and prognosis of RCC. Compared with the H19 rs2839698 CC genotype, the variant genotypes (CT/TT) were significantly associated with increased risk of RCC (P = 0.023, OR = 1.21; 95% CI = 1.03-1.45). Besides, patients with variant genotypes (CT/TT) were more likely to develop large tumor (P = 0.003, OR = 1.47; 95% CI = 1.16-1.85) and advanced disease (P = 0.010, OR = 1.59; 95% CI = 1.12-2.26); and had a significantly unfavorable overall survival than those with the rs2839698 CC genotype (CT/TT vs. CC: Log-rank P = 0.026, HR = 2.25, 95%CI = 1.07-4.75). Furthermore, the CT/TT genotypes were associated with significantly increased expression of H19 in renal tissue. The luciferase reporter assays revealed the potential effect of rs2839698 variant on the binding of microRNAs to H19. Our results suggest that the H19 rs2839698 variant may be a genetic predictor of susceptibility and mortality of RCC. The risk effects and the functional impact of the variant on H19 still need further validation.

Keywords: H19; genetic variation; mortality; renal cell carcinoma; susceptibility.

Copyright © 2020 Cao, Li, Cao, Qian, Du, Li, Wang, Qin, Shao, Zhang, Lu and Wang.

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Front Oncol
. 2020 May 19;10:755. doi: 10.3389/fonc.2020.00755. eCollection 2020.
Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer
Yujiro Hayashi 1, Kazutoshi Fujita 1, Kyosuke Matsuzaki 1, Marie-Lisa Eich 2 3, Eisuke Tomiyama 1, Makoto Matsushita 1, Yoko Koh 1, Kosuke Nakano 1, Cong Wang 1, Yu Ishizuya 1, Taigo Kato 1 4, Koji Hatano 1, Atsunari Kawashima 1, Takeshi Ujike 1, Motohide Uemura 1 4, Ryoichi Imamura 1, George J Netto 2, Norio Nonomura 1
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PMID: 32509577 PMCID: PMC7250242 DOI: 10.3389/fonc.2020.00755
Abstract
Recent studies showed the clinical utility of next-generation sequencing of urinary cell-free DNA (cfDNA) from patients with urothelial bladder cancer (UBC). In this study, we aimed to develop urinary cfDNA analysis by droplet digital PCR (ddPCR) as a high-throughput and rapid assay for UBC detection and prognosis. We analyzed urinary cfDNA of 202 samples from 2 cohorts. Test cohort was designed for investigating clinical utility of urinary cfDNA, and was composed of 74 samples from patients with UBC, and 52 samples of benign hematuria patients. Validation cohort was designed for validation and assessment of clinical utility comparing urinary cfDNA with UroVysion (Abbott, Illinois, USA), and was composed of 40 samples from patients with UBC, and 36 prospectively collected samples from patients under surveillance after surgery for urothelial carcinoma. We performed ddPCR analysis of hotspot gene mutations (TERT promoter and FGFR3). In the test cohort, the sensitivity of urinary cfDNA diagnosis was 68.9% (51/74) and the specificity was 100% in patients with UBC. The sensitivity increased to 85.9% when used in conjunction with urine cytology. In addition, patients with high TERT C228T allele frequency (≥14%) had significantly worse prognosis in bladder tumor recurrence than patients with low TERT C228T allele frequency or negative TERT C228T (p = 0.0322). In the validation cohort, the sensitivity of urinary cfDNA was 57.5% (23/40) and the specificity was 100% in UBC patients. The sensitivity of the combination of urine cytology with our hotspot analysis (77.5%) was higher than that of urine cytology with UroVysion (68.9%). In the post-surgical surveillance group, patients positive for the TERT C228T mutation had significantly worse prognosis for bladder tumor recurrence than mutation negative patients (p < 0.001). In conclusion, ddPCR analysis of urinary cfDNA is a simple and promising assay for the clinical setting, surpassing UroVysion for detection and prognosis determination in UBC.

Keywords: FGFR3; PCR; TERT promoter; UroVysion; bladder cancer; cell-free DNA; liquid biopsy; prognosis.

Copyright © 2020 Hayashi, Fujita, Matsuzaki, Eich, Tomiyama, Matsushita, Koh, Nakano, Wang, Ishizuya, Kato, Hatano, Kawashima, Ujike, Uemura, Imamura, Netto and Nonomura.

29 references4 figures
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Front Oncol
. 2020 May 19;10:756. doi: 10.3389/fonc.2020.00756. eCollection 2020.
MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM
Ramesh Elango 1, Khalid A Alsaleh 2, Radhakrishnan Vishnubalaji 1, Muthurangan Manikandan 3, Arwa M Ali 4 5, Nashwa Abd El-Aziz 5 6, Abdulrhaman Altheyab 2, Ammar Al-Rikabi 7, Musaad Alfayez 3, Abdullah Aldahmash 3, Nehad M Alajez 1
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PMID: 32509578 PMCID: PMC7248321 DOI: 10.3389/fonc.2020.00756
Abstract
Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61-0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59-0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.

Keywords: breast cancer; hsa-miR-205-5p; hsa-miR-214-3p; lymph node metastasis; miRNA signature.

Copyright © 2020 Elango, Alsaleh, Vishnubalaji, Manikandan, Ali, Abd El-Aziz, Altheyab, Al-Rikabi, Alfayez, Aldahmash and Alajez.

45 references7 figures
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17
Front Oncol
. 2020 May 20;10:595. doi: 10.3389/fonc.2020.00595. eCollection 2020.
Development and Clinical Validation of a Novel 4-Gene Prognostic Signature Predicting Survival in Colorectal Cancer
Yihang Yuan 1, Ji Chen 1, Jue Wang 1, Ming Xu 1, Yunpeng Zhang 1, Peng Sun 1, Leilei Liang 1
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PMID: 32509568 PMCID: PMC7251179 DOI: 10.3389/fonc.2020.00595
Abstract
In this study, we collected genes related to energy metabolism, used gene expression data from public databases to classify molecular subtypes of colon cancer (COAD) based on the genes related to energy metabolism, and further evaluated the relationships between the molecular subtypes and prognosis and clinical characteristics. Differential expression analysis of the molecular subtypes yielded 1948 differentially expressed genes (DEGs), whose functions were closely related to the occurrence and development of cancer. Based on the DEGs, we constructed a 4-gene prognostic risk model and identified the high expression of FOXD4, ENPEP, HOXC6, and ALOX15B as a risk factor associated with a high risk of developing COAD. The 4-gene signature has strong robustness and a stable predictive performance in datasets from different platforms not only in patients with early COAD but also in all patients with colon cancer. The enriched pathways of the 4-gene signature in the high- and low-risk groups obtained by GSEA were significantly related to the occurrence and development of colon cancer. Moreover, the results of qPCR, immunohistochemistry staining and Western blot assay revealed that FOXD4, ENPEP, HOXC6, and ALOX15B are over expressed in CRC tissues and cells. These results suggesting that the signature could potentially be used as a prognostic marker for clinical diagnosis.

Keywords: colon cancer; energy metabolism; genes; prognosis; survival.

Copyright © 2020 Yuan, Chen, Wang, Xu, Zhang, Sun and Liang.

33 references11 figures
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Front Oncol
. 2020 May 20;10:786. doi: 10.3389/fonc.2020.00786. eCollection 2020.
Development and Validation of a Comprehensive Multivariate Dosimetric Model for Predicting Late Genitourinary Toxicity Following Prostate Cancer Stereotactic Body Radiotherapy
Luca F Valle 1, Dan Ruan 1, Audrey Dang 1, Rebecca G Levin-Epstein 1, Ankur P Patel 2, Joanne B Weidhaas 1, Nicholas G Nickols 1, Percy P Lee 1, Daniel A Low 1, X Sharon Qi 1, Christopher R King 1, Michael L Steinberg 1, Patrick A Kupelian 1, Minsong Cao 1, Amar U Kishan 1
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PMID: 32509582 PMCID: PMC7251156 DOI: 10.3389/fonc.2020.00786
Abstract
Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Keywords: dose volume histogram (DVH); late toxicity; machine learning; multivariate; prediction model; prostate cancer; stereotactic body radiation therapy.

Copyright © 2020 Valle, Ruan, Dang, Levin-Epstein, Patel, Weidhaas, Nickols, Lee, Low, Qi, King, Steinberg, Kupelian, Cao and Kishan.

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19
Front Oncol
. 2020 May 20;10:677. doi: 10.3389/fonc.2020.00677. eCollection 2020.
Prognostic Role of Serum Lactate Dehydrogenase in Patients With Urothelial Carcinoma: A Systematic Review and Meta-Analysis
Minhong Wu 1, Pengxiu Lin 1, Lifang Xu 2, Zhiling Yu 1, Qingsheng Chen 1, Hongyong Gu 1, Cailing Liu 1
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PMID: 32509573 PMCID: PMC7252225 DOI: 10.3389/fonc.2020.00677
Abstract
Background: To investigate the potential prognostic role of serum lactate dehydrogenase (LDH) in patients with urothelial carcinoma (UC) using the method of systematic review and meta-analysis. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies up to February 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the relationship. Results: A total of 14 studies including 4,009 patients with UC were incorporated. The results showed that a high pretreatment serum LDH was associated with an inferior overall survival (OS, HR 1.61, 95% CI 1.39-1.87, p < 0.001), cancer-specific survival (CSS, HR 1.41, 95% CI 1.05-1.90, p = 0.022), and disease-free survival (DFS, HR 1.64, 95% CI 1.04-2.59, p = 0.034) in UC. Subgroup analyses identified that a high pretreatment serum LDH was associated with a poor OS (HR 1.97, 95% CI 1.02-3.81, p = 0.042) and DFS (HR 1.64, 95% CI 1.04-2.59, p = 0.034) in upper tract urothelial carcinoma, a short OS (HR 1.71, 95% CI 1.37-2.15, p < 0.001) in urothelial carcinoma of bladder. Conclusion: Our findings indicated that a high level of pretreatment serum LDH was associated with inferior OS, CSS, and DFS in patients with UC. This biomarker can be an important factor incorporated into the prognostic models for UC.

Keywords: lactate dehydrogenase; meta-analysis; prognosis; systematic review; urothelial carcinoma.

Copyright © 2020 Wu, Lin, Xu, Yu, Chen, Gu and Liu.

35 references4 figures
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Front Oncol
. 2020 May 20;10:633. doi: 10.3389/fonc.2020.00633. eCollection 2020.
Long Non-coding RNA AK025387 Promotes Cell Migration and Invasion of Gastric Cancer
Yi-Yuan Sun 1 2, Hui Zhang 1 2, Ran-Ran Ma 1 2, Guo-Hao Zhang 1 2, Ya-Ru Tian 1 2, Lei Liu 1 2, Lin Liu 1 2, Peng Gao 1 2
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PMID: 32509569 PMCID: PMC7251172 DOI: 10.3389/fonc.2020.00633
Abstract
Gastric cancer is one of the most common cancers in the world, and long non-coding RNAs (lncRNAs) play a crucial role in proliferation, metastasis, and invasion of gastric cancer. However, there are very few researches focusing on the effects of lncRNAs on metastatic gastric cancer. In this research, we identify one kind of lncRNA, called AK025387, which is highly expressed in metastatic gastric cancer samples compared with non-metastatic gastric cancer samples. The expression of AK025387 is significantly positively correlated with lymph node metastasis. The in situ hybridization demonstrates that AK025387 is located in both nucleus and cytoplasm, but mostly in cytoplasm. AK025387 promotes gastric cancer cells migratory and invasive ability, but it inhibits apoptosis in vitro. Furthermore, AK025387 regulates Raf-1, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated kinase (ERK) and is involved in mitogen-activated protein kinase (MAPK) signaling pathway to perform its biological functions. We conclude that AK025387 is highly expressed in metastatic gastric cancer, and its biological functions suggest the potential of AK025387 to be a biomarker of metastatic gastric cancer.

Keywords: AK025387; MAPK signaling pathway; gastric cancer; long non-coding RNA; migration and invasion.

Copyright © 2020 Sun, Zhang, Ma, Zhang, Tian, Liu, Liu and Gao.

28 references4 figures
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Front Oncol
. 2020 May 19;10:770. doi: 10.3389/fonc.2020.00770. eCollection 2020.
Mitochondrial Dysfunction Inhibits Hypoxia-Induced HIF-1α Stabilization and Expression of Its Downstream Targets
Marike W van Gisbergen 1, Kelly Offermans 1, An M Voets 2, Natasja G Lieuwes 1, Rianne Biemans 1, Roland F Hoffmann 3, Ludwig J Dubois 1, Philippe Lambin 1
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PMID: 32509579 PMCID: PMC7248342 DOI: 10.3389/fonc.2020.00770
Abstract
mtDNA variations often result in bioenergetic dysfunction inducing a metabolic switch toward glycolysis resulting in an unbalanced pH homeostasis. In hypoxic cells, expression of the tumor-associated carbonic anhydrase IX (CAIX) is enhanced to maintain cellular pH homeostasis. We hypothesized that cells with a dysfunctional oxidative phosphorylation machinery display elevated CAIX expression levels. Increased glycolysis was observed for cytoplasmic 143B mutant hybrid (m.3243A>G, >94.5%) cells (p < 0.05) and 143B mitochondrial DNA (mtDNA) depleted cells (p < 0.05). Upon hypoxia (0.2%, 16 h), genetic or pharmacological oxidative phosphorylation (OXPHOS) inhibition resulted in decreased CAIX (p < 0.05), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α) expression levels. Reactive oxygen species (ROS) and prolyl-hydroxylase 2 (PHD2) levels could not explain these observations. In vivo, tumor take (>500 mm3) took longer for mutant hybrid xenografts, but growth rates were comparable with control tumors upon establishment. Previously, it has been shown that HIF-1α is responsible for tumor establishment. In agreement, we found that HIF-1α expression levels and the pimonidazole-positive hypoxic fraction were reduced for the mutant hybrid xenografts. Our results demonstrate that OXPHOS dysfunction leads to a decreased HIF-1α stabilization and subsequently to a reduced expression of its downstream targets and hypoxic fraction in vivo. In contrast, hypoxia-inducible factor 2-alpha (HIF-2α) expression levels in these xenografts were enhanced. Inhibition of mitochondrial function is therefore an interesting approach to increase therapeutic efficacy in hypoxic tumors.

Keywords: CAIX; HIF-1α; Metformin; OXPHOS; mitochondria; mtDNA.

Copyright © 2020 van Gisbergen, Offermans, Voets, Lieuwes, Biemans, Hoffmann, Dubois and Lambin.

67 references5 figures
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Front Oncol
. 2020 May 19;10:635. doi: 10.3389/fonc.2020.00635. eCollection 2020.
Use of a Si/CdTe Compton Camera for In vivo Real-Time Monitoring of Annihilation Gamma Rays Generated by Carbon Ion Beam Irradiation
Shintaro Shiba 1 2, Raj Kumar Parajuli 2 3, Makoto Sakai 2, Takahiro Oike 1, Tatsuya Ohno 2, Takashi Nakano 1 3
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PMID: 32509570 PMCID: PMC7248380 DOI: 10.3389/fonc.2020.00635
Abstract
The application of annihilation gamma-ray monitoring to the adaptive therapy of carbon ion radiotherapy (C-ion RT) requires identification of the peak intensity position and confirmation of activated elements with annihilation gamma-rays generated at the C-ion-irradiated site from those transported to unirradiated sites. Real-time monitoring of C-ion-induced annihilation gamma-rays was implemented using a Compton camera in a mouse model. An adult C57BL/6 mouse was anesthetized, and C-ion beams were directed into the abdomen at 1 × 109 particles/s for 20 s. The 511 keV annihilation gamma-rays, generated by the interaction between the irradiated C-ion beam and the target mouse, were detected using a silicon/cadmium telluride (Si/CdTe) Compton camera for 20 min immediately after irradiation. The irradiated site and the peak intensity position of 511 keV gamma emissions due to C-ion beam irradiation on a mouse were observed at the abdomen of the mouse by developing Compton images. Moreover, the positron emitter transport was observed by evaluating the range of gamma-ray emission after the C-ion beam irradiation on the mouse. Our data suggest that by confirming the peak intensity and beam range of C-ion RT with Si/CdTe-based Compton camera, it would be possible to reduce the intra-fractional and inter-fractional dose distribution degradation. Therefore, the results of this study would contribute to the future development of adaptive therapy with C-ion RT for humans.

Keywords: Compton camera; activated elements with annihilation gamma-ray transport visualization; adaptive therapy; annihilation gamma-rays; carbon ion beams; irradiated site visualization.

Copyright © 2020 Shiba, Parajuli, Sakai, Oike, Ohno and Nakano.

52 references4 figures
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Review Front Oncol
. 2020 May 19;10:815. doi: 10.3389/fonc.2020.00815. eCollection 2020.
Hyperviscosity Syndrome in Paraprotein Secreting Conditions Including Waldenstrom Macroglobulinemia
Allison Weaver 1, Samuel Rubinstein 1, Robert F Cornell 1
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PMID: 32509586 PMCID: PMC7248405 DOI: 10.3389/fonc.2020.00815
Abstract
Hyperviscosity syndrome is a serious complication associated with high levels of paraproteins in patients with hematological malignancies. Therapeutic advances in disease control may reduce the incidence of hyperviscosity syndrome; however, management of acute cases requires an understanding of key symptoms and prompt treatment to mitigate serious consequences.

Keywords: Waldenstrom; chemotherapy; hyperviscosity; lymphoma; plasma exchange.

Copyright © 2020 Weaver, Rubinstein and Cornell.

37 references1 figure
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