Rapid Identification of Key Copy Number Alterations in B- and T-Cell Acute Lymphoblastic Leukemia by Digital Multiplex Ligation-Dependent Probe Amplification
Recurrent clonal genetic alterations are the hallmark of Acute Lymphoblastic Leukemia (ALL) and govern the risk stratification, response to treatment and clinical outcome. In this retrospective study conducted on ALL patient samples, the purpose was to estimate the copy number alterations (CNAs) in ALL by digitalMLPA (dMLPA), validation of the dMLPA data by conventional MLPA and RT-PCR, and correlation of CNAs with Minimal Residual Disease (MRD) status. The ALL patient samples (n = 151; B-ALL, n = 124 cases and T-ALL, n = 27 cases) were assessed for CNAs by dMLPA for detection of sub-microscopic CNAs and ploidy status. Thi...
Source: Frontiers in Oncology - September 13, 2019 Category: Cancer & Oncology Source Type: research

The Highly Pure Neem Leaf Extract, SCNE, Inhibits Tumorigenesis in Oral Squamous Cell Carcinoma via Disruption of Pro-tumor Inflammatory Cytokines and Cell Signaling
Oral squamous cell carcinoma (OSCC) is a deadly disease that comprises 60% of all head and neck squamous cell cancers. The leaves of the Neem tree (Azadirachta indica) have been used in traditional Ayurvedic medicine for centuries to treat numerous oral maladies and are known to have significant anti-inflammatory properties. We hypothesize that a highly pure super critical CO2 Neem leaf extract (SCNE) prevents initiation and progression of OSCC via downregulation of intra-tumor pro-inflammatory pathways, which promote tumorigenesis. Hence, we investigated the anticancer effects of SCNE using in vitro and in vivo platforms....
Source: Frontiers in Oncology - September 13, 2019 Category: Cancer & Oncology Source Type: research

Development of Patient-Derived Preclinical Platform for Metastatic Pancreatic Cancer: PDOX and a Subsequent Organoid Model System Using Percutaneous Biopsy Samples
This study describes the development of patient-derived preclinical platform using very small sized-percutaneous liver gun biopsy (PLB) of metastatic pancreatic cancer, based on patient-derived xenograft (PDX)-mediated tissue amplification and subsequent organoid generation. To increase the success rate and shorten the tumor growth period, patient-derived orthotopic xenograft (PDOX) model was developed to directly implant threadlike PLB samples into the pancreas. The engraftment success rate of PDOX samples from 35 patients with metastatic PDAC was 47%, with these samples showing the potential to metastasize to distant org...
Source: Frontiers in Oncology - September 13, 2019 Category: Cancer & Oncology Source Type: research

Association Between Serum Cotinine Level and Serological Markers of Epstein –Barr Virus in Healthy Subjects in South China Where Nasopharyngeal Carcinoma Is Endemic
Conclusions: Higher serum cotinine level is associated with higher seropositivity for EBV serological markers in healthy men in southern China. Such positive association was also observed in women but became non-significant. If confirmed to be causal, this finding has important implications for tobacco control and prevention of EBV-related disease, particularly for NPC. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 13, 2019 Category: Cancer & Oncology Source Type: research

MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations
MicroRNAs (miRNAs) are a family of highly conserved, non-coding single-stranded RNAs transcribed as ~70 nucleotide precursors to an 18–22 nucleotide product (1). miRNAs can silence their homologous target genes at the post-transcriptional level, and these genes have been revealed to play an important role in tumorigenesis, invasion and metastasis (2). MicroRNA-27a (miR-27a), transcripted by miR-27a gene, has proved to implicate with many kinds of solid tumors, showing potential as a useful biomarker or drug target for clinical application. However, even though miR-27a has been reported in many cancers, the mechanism ...
Source: Frontiers in Oncology - September 12, 2019 Category: Cancer & Oncology Source Type: research

Optical Molecular Imaging of Inflammatory Cells in Interventional Medicine –An Emerging Strategy
The optical molecular imaging of inflammation is an emerging strategy for interventional medicine and diagnostics. The host's inflammatory response and adaptation to acute and chronic diseases provides unique signatures that have the potential to guide interventions. Thus, there are emerging a suite of molecular imaging and sensing approaches for a variety of targets in this area. This review will focus on two key cellular orchestrators that dominate this area, neutrophils and macrophages, with recent developments in molecular probes and approaches discussed. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 12, 2019 Category: Cancer & Oncology Source Type: research

Circulating MicroRNAs as Biomarkers for Prostate Cancer Detection and Metastasis Development Prediction
Prostate Cancer (PCa) overdiagnosis and overtreatment, as a consequence of the limited specificity of current detection and prognostication methods, remains a major challenge in clinical practice. Therefore, development and validation of new molecular biomarkers amenable of detecting clinically significant disease is crucial. MicroRNAs (miRNA) deregulation is common in cancer, constituting potential non-invasive biomarkers for PCa detection and prognostication. Herein, we evaluated the screening and prognostic biomarker potential of two onco-microRNAs (miR-182-5p and miR-375-3p) in liquid biopsies (plasma) of PCa patients ...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Long Non-coding RNAs as Functional and Structural Chromatin Modulators in Acute Myeloid Leukemia
Acute myeloid leukemia is a hematopoietic neoplasm of dismal prognosis that results from the accumulation of immature myeloid blasts in the bone marrow and the peripheral blood. It is strongly dependent on epigenetic regulation for disease onset, maintenance and in response to treatment. Epigenetic regulation refers to the multiple chemical modifications of DNA or DNA-associated proteins that alter chromatin structure and DNA accessibility in a heritable manner, without changing DNA sequence. Unlike sequence-specific transcription factors, epigenetic regulators do not necessarily bind DNA at consensus sequences, but still ...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Overexpression of p16INK4a Serves as Prognostic Marker in Squamous Cell Vulvar Cancer Patients Treated With Radiotherapy Irrespective of HPV-Status
Conclusions: Patients with cHPPVC, indicating an etiological relevance of HPV in the respective tumors, showed a better, albeit not significant, prognosis. The sole detection of p16INK4a-overexpression is a prognostic factor for survival in vulvar cancer and indicates better prognosis after radiotherapy, independent of detection of HPV DNA. p16INK4a should be used as surrogate marker for HPV-driven carcinogenesis in vulvar cancer with caution. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Integrated Transcriptome Analysis Reveals KLK5 and L1CAM Predict Response to Anlotinib in NSCLC at 3rd Line
The oral multi-targeted tyrosine kinase inhibitor (TKI) anlotinib is effective for non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, a fraction of patients remains non-responsive, raising the need of how to identify anlotinib-responsive patients. In the present study, we aimed to screen potential biomarkers for anlotinib-responsive stratification via integrated transcriptome analysis. Comparing with the anlotinib-sensitive lung cancer cell NCI-H1975, we found 1,315 genes were differentially expressed in anlotinib-resistant NCI-H1975 cells. Among the enriched angiogenesis-related genes, we observed...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Long Non-coding RNA ANRIL in the Nucleus Associates With Periostin Expression in Breast Cancer
The long non-coding RNA (LncRNA) antisense RNA in the INK4 locus (ANRIL) is overexpressed in several cancers including breast cancer. To better understand the role of ANRIL in breast cancer this study investigated where ANRIL was expressed in breast tumors using in situ hybridization by RNAscope. Additional RNAscope assays for IL6, CCL2, and POSTN were used to establish whether ANRIL correlated with increased tumor promoting cytokines. Breast tumors with ANRIL over expressed from real-time quantitative (RT-q) PCR assays were selected for analysis using RNAscope. All tumors showed ANRIL expression in malignant cells, but am...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Past, Current, and Future of Immunotherapies for Prostate Cancer
Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of cancer related death in men in Western countries. The standard therapy for metastatic PCa is androgen suppression therapy (AST). Men undergoing AST eventually develop metastatic castration-resistant prostate cancer (mCRPC), of which there are limited treatment options available. Immunotherapy has presented substantial benefits for many types of cancer, but only a marginal benefit for mCRPC, at least in part, due to the immunosuppressive tumor microenvironment (TME). Current clinical trials are investigating monotherapies or combination ...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Expression of Programmed Cell Death-Ligands in Hepatocellular Carcinoma: Correlation With Immune Microenvironment and Survival Outcomes
In this study, immunohistochemistry (IHC) data from 304 HCC patients were used to determine the clinicopathological features of PD-L1 and PD-L2 and their correlation with CD8+ T cells in HCC. Moreover, fresh clinical HCC samples were used to identify the immune cell subtypes expressing PD-L1 and PD-L2. By using The Cancer Genome Atlas (TCGA) dataset, we further assessed the correlation between mutation signature, copy number variation (CNV), number of neoepitopes, immune gene expression, immune/stromal cell infiltration to the expression of PD-L1 and PD-L2. While membrane expression of PD-L2 was observed in 19.1% of tumor ...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Non-invasive Bioluminescence Monitoring of Hepatocellular Carcinoma Therapy in an HCR Mouse Model
In this study, we developed a novel animal model for the fast assessment of drug efficacy against primary HCC in vivo. HCC was induced in immunocompetent hepatocarcinogenesis reporter (HCR) mice by diethylnitrosamine (DEN) injection and confirmed by histopathological staining. Using the bioluminescence imaging (BLI) technique, HCC progression was longitudinally visualized and monitored in a non-invasive way. Tests of two clinical drugs showed that both sorafenib and oxaliplatin significantly inhibited the BLI signal in mouse liver in a dose-dependent manner. The in vivo intensity of BLI signals was highly consistent with t...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma
OTUD7B, a multifunctional deubiquitinylase, plays an essential role in inflammation and proliferation signals. However, its function in lung cancer remains largely unknown. The aim of this study was to evaluate the prognostic significance of OTUD7B in patients with lung adenocarcinoma and squamous carcinoma and to characterize its molecular mechanisms in lung cancer progression and metastasis. Two tissue microarrays containing 150 pairs of lung squamous carcinoma and matched adjacent non-cancer tissues, and one tissue microarray containing 75 pairs of lung adenocarcinoma and adjacent non-cancer tissues were included, and i...
Source: Frontiers in Oncology - September 11, 2019 Category: Cancer & Oncology Source Type: research

Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma
Background and Objective: Radiation-induced lymphopenia has a tangible impact on overall survival (OS) in multiple solid tumors. We investigated the association between circulating lymphocyte populations (CLPs) before and after stereotactic body radiation therapy (SBRT) and OS in patients with hepatocellular carcinoma (HCC).Materials and Methods: Seventy-eight HCC patients treated with SBRT between January 2013 and June 2017 were retrospectively analyzed. Baseline and post-treatment total peripheral lymphocyte counts (TPLCs) and values of different CLPs were obtained and analyzed for clinical outcomes. Univariate and multi...
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation
High-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in patients with malignant lymphomas. In Europe over 8,000 ASCTs for lymphoma were performed out of a total of 40,000 transplants according to the European Bone Marrow Transplant (EBMT) activity survey in 2017. ASCT is considered the standard treatment for eligible patients failing to achieve remission after first line chemotherapy or patients with relapsed or refractory lymphomas, including classical Hodkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, as well as con...
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

A Pilot Study of Radiotherapy and Local Hyperthermia in Elderly Patients With Muscle-Invasive Bladder Cancers Unfit for Definitive Surgery or Chemoradiotherapy
Conclusions: The outcomes from this pilot study indicate that thermoradiotherapy is a feasible therapeutic modality in elderly MIBC patients unfit for surgery or CTRT. HTRT is well-tolerated, allows bladder preservation and function, achieves long-term satisfactory locoregional control and is devoid of significant treatment-related morbidity. This therapeutic approach deserves further evaluation in randomized studies. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Current Advance of Therapeutic Agents in Clinical Trials Potentially Targeting Tumor Plasticity
Tumor plasticity refers to tumor cell's inherent property of transforming one type of cell to different types of cells. Tumor plasticity is the main cause of tumor relapse, metastasis and drug resistance. Cancer stem cell (CSC) model embodies the trait of tumor plasticity. During carcinoma progression, epithelial-mesenchymal transition (EMT) plays crucial role in the formation of CSCs and vasculogenic mimicry (VM) based on epithelial-mesenchymal plasticity. And the unique tumor microenvironment (TME) not only provides suitable niche for CSCs but promotes the building of CSCs and VM that nourishes tumor tissue together with...
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Expression Profiling of Circulating Tumor Cells in Pancreatic Ductal Adenocarcinoma Patients: Biomarkers Predicting Overall Survival
The interest in liquid biopsy is growing because it could represent a non-invasive prognostic or predictive tool for clinical outcome in patients with pancreatic ductal adenocarcinoma (PDAC), an aggressive and lethal disease. In this pilot study, circulating tumor cells (CTCs), CD16 positive atypical CTCs, and CTC clusters were captured and characterized in the blood of patients with PDAC before and after palliative first line chemotherapy by ScreenCell device, immunohistochemistry, and confocal microscopy analysis. Gene profiles were performed by digital droplet PCR in isolated CTCs, five primary PDAC tissues, and three d...
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Quality of Life Outcomes Following Organ-Sparing SBRT in Previously Irradiated Recurrent Head and Neck Cancer
Conclusions: OARExtreme-sparing SBRT is able to achieve excellent tumor coverage while protecting the organs at highest risk of re-irradiation-related complications. The potential for lower toxicities and maintained QoL with this treatment makes it a promising option for salvage of recurrent head and neck cancer.SummaryLocal control and overall survival rates for recurrent head and neck cancer remain poor, despite the use of local therapy. In addition, re-irradiation with conventional radiation therapy confers a high rate of grade 3 and higher late toxicities. SBRT appears to improve the therapeutic ratio in this patient p...
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Part I of GANNET53: A European Multicenter Phase I/II Trial of the Hsp90 Inhibitor Ganetespib Combined With Weekly Paclitaxel in Women With High-Grade, Platinum-Resistant Epithelial Ovarian Cancer —A Study of the GANNET53 Consortium
Conclusions: The combination of ganetespib 150 mg/m2 with paclitaxel 80 mg/m2 once weekly for 3 out of 4 weeks was generally well-tolerated with no DLTs, and therefore chosen for the randomized phase II trial. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

Development and Validation of an Autophagy Score Signature for the Prediction of Post-operative Survival in Colorectal Cancer
Conclusions: The identification of robust autophagy-related features can effectively classify CRC patients into groups with low and high risk of early relapse. This signature may be used to help select high-risk CRC patients who require more aggressive treatment interventions. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 9, 2019 Category: Cancer & Oncology Source Type: research

Towards a Better Understanding of Cohesin Mutations in AML
Classical driver mutations in acute myeloid leukemia (AML) typically affect regulators of cell proliferation, differentiation, and survival. The selective advantage of increased proliferation, improved survival, and reduced differentiation on leukemia progression is immediately obvious. Recent large-scale sequencing efforts have uncovered numerous novel AML-associated mutations. Interestingly, a substantial fraction of the most frequently mutated genes encode general regulators of transcription and chromatin state. Understanding the selective advantage conferred by these mutations remains a major challenge. A striking exam...
Source: Frontiers in Oncology - September 9, 2019 Category: Cancer & Oncology Source Type: research

Dysregulation of miR-375/AEG-1 Axis by Human Papillomavirus 16/18-E6/E7 Promotes Cellular Proliferation, Migration, and Invasion in Cervical Cancer
Cervical Cancer (CC) is a highly aggressive tumor and is one of the leading causes of cancer-related deaths in women. miR-375 was shown to be significantly down-regulated in cervical cancer cells. However, the precise biological functions of miR-375 and the molecular mechanisms underlying its action in CC are largely unknown. miR-375 targets were predicted by bioinformatics target prediction tools and validated using luciferase reporter assay. Herein, we investigated the functional significance of miR-375 and its target gene in CC to identify potential new therapeutic targets. We found that miR-375 expression was significa...
Source: Frontiers in Oncology - September 9, 2019 Category: Cancer & Oncology Source Type: research

Radiation-Induced Lung Injury (RILI)
Radiation pneumonitis (RP) and radiation fibrosis (RF) are two dose-limiting toxicities of radiotherapy (RT), especially for lung and esophageal cancer. It occurs in 5-20% of patients and limits the maximum dose that can be delivered, reducing tumor control probability (TCP) and may lead to dyspnea, lung fibrosis and impaired quality of life. Both physical and biological factors determine the normal tissue complication probability (NTCP) by Radiotherapy. A better understanding of the pathophysiological sequence of radiation-induced lung injury (RILI) and the intrinsic, environmental and treatment-related factors may aid in...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Glioblastoma and Anaplastic Astrocytoma: Differentiation Using MRI Texture Analysis
Conclusion Our study shows that MRI texture analysis using LDA algorithm had promising ability to discriminate glioblastoma from ANA. Multi-center studies with greater number of patients are warranted in future studies to confirm the preliminary result. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Histone Deacetylase 4 Promotes Osteosarcoma Cell Proliferation and Invasion by Regulating Expression of Proliferating Cell Nuclear Antigen
Conclusions: Our findings suggest that HDAC4 could promote OS cell proliferation and invasion by regulating the expression of PCNA. Thus, our research indicates that HDAC4 may be a potential target for therapy in OS. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Development and External Validation of a Novel 12-Gene Signature for Prediction of Overall Survival in Muscle-Invasive Bladder Cancer
Purpose: We aimed to develop and validate a novel gene signature from published data and improve the prediction of survival in muscle-invasive bladder cancer (MIBC). Methods: We searched the published gene signatures associated with the overall survival (OS) of MIBC and compiled all 274 genes to develop a novel gene signature. RNAseq data of TCGA (the Cancer Genome Atlas) bladder cohort were downloaded. All genes were included in a univariate Cox hazard ratio model. We then used a reduced multivariate Cox regression model, which included only genes achieving P (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy for which treatment options have been largely limited to cytotoxic chemotherapy for the past four decades. Next-generation sequencing and other approaches have identified a spectrum of genomic and epigenomic alterations that contribute to AML initiation and maintenance. The key role of epigenetic modifiers and the reversibility of epigenetic changes have paved the way for evaluation of a new set of drug targets, and facilitated the design of novel candidate treatment strategies. More recently, seven new targeted therapies have been FDA-approved demonstr...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Fluorescence Diagnosis in Neurooncology: Retrospective Analysis of 653 Cases
Conclusion. Based on a large series of our patients with a great variety of histological tumor types, it was concluded, that a neurosurgeon can predict fluorescence sensitivity before surgery. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Dramatic Response of Leptomeningeal Carcinomatosis to Nivolumab in PD-L1 Highly Expressive Non-small Cell Lung Cancer: A Case Report
In a patient who had been diagnosed of located squamous cell lung carcinoma, pneumonectomy and adjuvant chemotherapy were performed. Brain recurrence and subsequent lung metastatic disease were uncontrolled by neurosurgery, holocranial radiotherapy and first-line chemotherapy. In August 2015, appearance of leptomeningeal carcinomatosis triggered severe clinical deterioration and threatened the patient's life. Anti-PD1 immune checkpoint inhibitor Nivolumab was initiated in an attempt to stop tumour growth, achieving a spectacular brain and pulmonary complete response and clinical improvement, without serious adverse effects...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Identification of Eight Small Nucleolar RNAs as Survival Biomarkers and Their Clinical Significance in Gastric Cancer
In conclusion, we identified an eight-snoRNA risk signature to predict overall survival of gastric cancer patients. Seven of these snoRNAs were associated with clinical features of the disease. Knocking down U66 inhibited cell proliferation. These findings provide new clues with prognostic and therapeutic implications in gastric cancer. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

A Reappraisal of Thymosin Alpha1 in Cancer Therapy
Thymosin alpha1 (Tα1), an endogenous peptide first isolated from the thymic tissue in the mid-sixties, has gained considerable attention for its immunostimulatory activity that led to its application to diverse pathological conditions, including cancer. Studies in animal models and human patients have shown promising results in different types of malignancies, especially when Tα1 was used in combination with other chemo- and immune therapies. For this reason, the advancements in our knowledge on the adjuvant role of Tα1 have moved in parallel with the development of novel cancer therapies in a way that T&...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Persistent Basophilia May Suggest an “Accelerated Phase” in the Evolution of CALR-Positive Primary Myelofibrosis Toward Acute Myeloid Leukemia
Basophils are white blood cells that play an important role in the human immune system. These cells physiologically increase in number in immune response to certain allergies, chronic inflammation and parasitic infections. But are also a significant indicator for the presence of certain malignancies such as chronic myeloproliferative neoplasms and acute myeloid leukemia. In the current manuscript we present a statistically significant correlation between increasing basophilia in primary myelofibrosis (PMF) and the risk for the subsequent development of an acute myeloid leukemia. We retrospectively identified in the fil...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Exosomes in Cancer Radioresistance
Radiation is a mainstay of cancer therapy. Radioresistance is a significant challenge in the treatment of locally advanced, recurrent and metastatic cancers. The mechanisms of radioresistance are complicated and still not completely understood. Exosomes are 40-150 nm vesicles released by cancer cells that contain pathogenic components, such as proteins, mRNAs, DNA fragments, non-coding RNAs and lipids. Exosomes play a critical role in cancer progression, including cell-cell communication, tumour-stromal interactions, activation of signaling pathways and immunomodulation. Emerging data indicate that radiation-derived exosom...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Monitoring Chronic Myeloid Leukemia: How Molecular Tools May Drive Therapeutic Approaches
More than 15 years ago, imatinib entered into the clinical practice as a “magic bullet”; from that point on, the prognosis of patients affected by chronic myeloid leukemia (CML) became comparable to that of aged-matched healthy subjects. The aims of treatment with tyrosine kinase inhibitors (TKIs) are complete hematological response after 3 months of treatment, complete cytogenetic response after 6 months, and a reduction of the molecular disease of at least 3 logs after 12 months. Patients who do not reach their goal can switch to another TKI. Thus, the molecular monitoring of response is the main consideratio...
Source: Frontiers in Oncology - September 6, 2019 Category: Cancer & Oncology Source Type: research

Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis
Tumor metastasis is a sequential event accounting for numerous cancer-related fatalities worldwide. The process of metastasis serially involves invasion, intravasation, extravasation and tumor growth at the secondary site. Migration and invasion enhancer 1 (MIEN1) is a membrane associated protein overexpressed in various human cancers. Biological activity of MIEN1 is driven by geranylgeranyltransferase-I mediated prenylation at CAAX motif and methylation of the prenylated protein that anchors MIEN1 into the cellular membrane. Post-translationally modified MIEN1 interacts with Syk kinase and Annexin A2 protein; polymerizes ...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Retrospective Multicenter Long-Term Follow-up Analysis of Prognostic Risk Factors for Recurrence-Free, Metastasis-Free, Cancer-Specific, and Overall Survival After Curative Nephrectomy in Non-metastatic Renal Cell Carcinoma
We evaluated prognostic risk factors of recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) outcomes in patients with non-metastatic renal cell carcinoma (nmRCC) after curative nephrectomy during long-term-follow-up. The medical records of 4260 patients with nmRCC who underwent curative nephrectomy between 2000 and 2012 from five Korean institutions and followed-up after postoperative 1-month until December 2017 were retrospectively analyzed for RFS, MFS, OS, and CSS. During the median 43.86 months of follow-up, 342 recurrences, 127 metastases, and 361 d...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Androgen Receptor Signaling in the Development of Castration-Resistant Prostate Cancer
Most prostate cancers are androgen-sensitive malignancies whose growths depend on the transcriptional activity of the androgen receptor (AR). In the 1940s, Charles Huggins demonstrated that the surgical removal of testes in men can result in a dramatic improvement in symptoms and can induce prostate cancer regression. Since then, androgen deprivation therapies have been the standard first-line treatment for advanced prostate cancer, including: surgical castration, medical castration, antiandrogens, and androgen biosynthesis inhibitors. These therapies relieve symptoms, reduce tumor burden, and prolong patient survival, whi...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Down Regulation of c-FLIPL Enhance PD-1 Blockade Efficacy in B16 Melanoma
Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a master anti-apoptotic regulator and is also thought to be the main causal factor of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expr...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells
Emerging evidence has shown that cinobufagin, as an active ingredient of Venenum Bufonis, inhibits tumor development. The aim of this study was to investigate the inhibitory effects of cinobufagin on A375 human malignant melanoma cells. MTT and colony formation assays showed that cinobufagin significantly inhibited A375 cell proliferation and cell colony formation. Additional studies demonstrated that cinobufagin markedly increased the levels of ATM serine/threonine kinase and checkpoint kinase 2 and decreased the levels of cell division cycle 25C, cyclin-dependent kinase 1, and cyclin B, subsequently inducing G2/M cell cy...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Standardization of Sequencing Coverage Depth in NGS: Recommendation for Detection of Clonal and Subclonal Mutations in Cancer Diagnostics
The insufficient standardisation of diagnostic next-generation sequencing (NGS) still limits its implementation in clinical practice, with the correct detection of mutations at low variant allele frequencies (VAF) facing particular challenges. We address here the standardisation of sequencing coverage depth in order to minimise the probability of false positive and false negative results, the latter being underestimated in clinical NGS. There is currently no consensus on the minimum coverage depth, and so each laboratory has to set its own parameters. To assist laboratories with the determination of the minimum coverage pa...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Effect of Radiotherapy Combined With Pembrolizumab on Local Tumor Control in Mucosal Melanoma Patients
Conclusions: Besides RT acting as an immune adjuvant, ICI might have a radiosensitizing effect and may increase LC without severe toxicity. We have initiated a phase II study to determine the effects of RT in patients with melanoma undergoing anti-PD1 (NCT04017897). (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Detection of POLE Subtypes in High-Grade Endometrioid Carcinoma by BaseScope-ISH Assay
CONCLUSION: In the case of high-grade EC, combined with morphological characteristics, the BaseScope assay can effectively and specifically identify POLE mutation cases, providing a reliable foundation for the application of clinical diagnosis and molecular classification. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

The Association Between the Incidence Risk of Peripheral Neuropathy and PD-1/PD-L1 Inhibitors in the Treatment for Solid Tumor Patients: A Systematic Review and Meta-Analysis
Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

An Engineered Fusion Protein Anti-CD19(Fab)-LDM Effectively Inhibits ADR-Resistant B Cell Lymphoma
The five-year survival rate of patients with B cell lymphoma is about 50% after initial diagnosis, mainly because of resistance to chemotherapy. Hence, it is necessary to understand the mechanism of chemo-resistance and to explore novel methods to circumvent multidrug resistance. Previously, we showed that an engineered cytotoxic fusion protein anti-CD19(Fab)-LDM (lidamycin), can induce apoptosis of B-lymphoma cells. Herein, we successfully established an adriamycin (ADR)-resistant B cell lymphoma cell line BJAB/ADR. The mRNA and protein level of ATP-binding cassette subfamily B member 1 (ABCB1) were significantly overexpr...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Risk Factors and Outcomes of Early Relapse After Curative Resection of Intrahepatic Cholangiocarcinoma
Early recurrence after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a great effect on the long-term survival outcomes of patients. We conducted this study to identify risk factors for early recurrence and clarify whether early recurrence is related to ICC patients’ long-term survival outcomes. 322 ICC patients who underwent partial hepatectomy at Liver Cancer Institute of Zhongshan Hospital between January 2005 and December 2011 were included in this retrospectively study. Early recurrence was defined as ICC recurrence within two years after hepatectomy. We identified a total of 168 patients with early r...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research

Computed Tomography Radiomic Nomogram for Preoperative Prediction of Extrathyroidal Extension in Papillary Thyroid Carcinoma
This study aimed to explore a radiomic model for preoperatively prediction of ETE in patients with PTC. Methods The study included 624 PTC patients (without ETE, n = 448; with minimal ETE, n = 52; with gross ETE, n = 124) whom were divided randomly into training (n = 437) and validation (n = 187) cohorts; all data were gathered between January 2016 and November 2017. Radiomic features were extracted from computed tomography (CT) images of PTCs. Key radiomic features were identified and incorporated into a radiomic signature. Combining the radiomic signature with clinical risk factors, a radiomic nomogram was constructed...
Source: Frontiers in Oncology - September 4, 2019 Category: Cancer & Oncology Source Type: research