1.
Front Oncol. 2020 Feb 28;10:301. doi: 10.3389/fonc.2020.00301. eCollection 2020.
Molecular Mechanisms of PALB2 Function and Its Role in Breast Cancer Management.
Abstract
Partner and localizer of BRCA2 (PALB2) is vital for homologous recombination (HR) repair in response to DNA double-strand breaks (DSBs). PALB2 functions as a tumor suppressor and participates in the maintenance of genome integrity. In this review, we summarize the current knowledge of the biological roles of the multifaceted PALB2 protein and of its regulation. Moreover, we describe the link between PALB2 pathogenic variants (PVs) and breast cancer predisposition, aggressive clinicopathological features, and adverse clinical prognosis. We also refer to both the opportunities and challenges that the identification of PALB2 PVs provides in breast cancer genetic counseling and precision medicine.
Copyright © 2020 Wu, Zhou, Zhang, Chen, Luo, Lu, Sun and Chen.
KEYWORDS:
PALB2; breast cancer; homologous recombination; pathogenic variants; precision medicine
2.
Front Oncol. 2020 Feb 28;10:279. doi: 10.3389/fonc.2020.00279. eCollection 2020.
Identifying BAP1 Mutations in Clear-Cell Renal Cell Carcinoma by CT Radiomics: Preliminary Findings.
Abstract
To evaluate the potential application of computed tomography (CT) radiomics in the prediction of BRCA1-associated protein 1 (BAP1) mutation status in patients with clear-cell renal cell carcinoma (ccRCC). In this retrospective study, clinical and CT imaging data of 54 patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database. Among these, 45 patients had wild-type BAP1 and nine patients had BAP1 mutation. The texture features of tumor images were extracted using the Matlab-based IBEX package. To produce class-balanced data and improve the stability of prediction, we performed data augmentation for the BAP1 mutation group during cross validation. A model to predict BAP1 mutation status was constructed using Random Forest Classification algorithms, and was evaluated using leave-one-out-cross-validation. Random Forest model of predict BAP1 mutation status had an accuracy of 0.83, sensitivity of 0.72, specificity of 0.87, precision of 0.65, AUC of 0.77, F-score of 0.68. CT radiomics is a potential and feasible method for predicting BAP1 mutation status in patients with ccRCC.
Copyright © 2020 Feng, Zhang, Qi, Shen, Hu and Chen.
KEYWORDS:
BAP1 mutation; CT; clear cell renal cell carcinoma; machine learning; radiomics
3.
Front Oncol. 2020 Feb 28;10:273. doi: 10.3389/fonc.2020.00273. eCollection 2020.
The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects.
Abstract
T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely "early T-cell precursors" lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance.
Copyright © 2020 Fattizzo, Rosa, Giannotta, Baldini and Fracchiolla.
KEYWORDS:
T-cell acute lymphoblastic leukemia; early T cell precursors acute lymphoblastic leukemia; genome; molecular; target therapies
4.
Front Oncol. 2020 Feb 28;10:270. doi: 10.3389/fonc.2020.00270. eCollection 2020.
Editorial: Emerging Translational Opportunities in Comparative Oncology with Companion Canine Cancers.
KEYWORDS:
cancer biology; cancer diagnostic; cancer therapy; canine; comparative oncology
5.
Front Oncol. 2020 Feb 28;10:268. doi: 10.3389/fonc.2020.00268. eCollection 2020.
Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer.
Abstract
Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.
Copyright © 2020 Kok.
KEYWORDS:
HNSCC; PD-1/PD-L1 signaling pathway; adapted resistance; cancer immunotherapy; head and neck cancer; immune checkpoint blockade; immune evasion; innate resistance
6.
Front Oncol. 2020 Feb 28;10:266. doi: 10.3389/fonc.2020.00266. eCollection 2020.
Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer.
Abstract
Background: Peritoneal dissemination is common in advanced ovarian cancer. The completeness of cytoreduction is an independent prognostic factor. The intraoperative fluorescence imaging via tumor-specific near-infrared fluorophore might improve staging and surgical completeness. A promising target for ovarian cancer is the gonadotropin-releasing hormone receptor (GnRHR). This study aimed to develop a GnRHR-targeted near-infrared imaging probe for the detection of peritoneal metastases of ovarian cancer. Methods: Indocyanine green (ICG) was conjugated with GnRH antagonist peptide to develop an ovarian cancer-selective fluorescence probe GnRHa-ICG. GnRHR expression was detected in ovarian cancer tissues. The binding capacity of GnRHa-ICG and ICG was detected in both cancer cell lines and mouse models of peritoneal metastatic ovarian cancer using fluorescence microscopy, flow cytometry, and near-infrared fluorescence imaging. Results: Tissue microarray analysis revealed the overexpression of GnRHR in ovarian cancer. GnRH-ICG exhibited the binding capacity in a panel of cancer cell lines with different expression levels of GnRHR. In ovarian cancer mouse models, GnRHa-ICG signals were detected in peritoneal tumor lesions rather than normal peritoneal and intestines tissues. ICG showed intensive fluorescence signals in intestines. The tumor-to-muscle ratio and tumor-to-intestine ratio of GnRHa-ICG was 7.41 ± 2.82 and 4.37 ± 1.66, higher than that of ICG (4.60 ± 0.50 and 0.57 ± 0.06) at 2 h post administration. The fluorescence signal of peritoneal metastases peaked in intensity at 2 h and maintained for up to 48 h. ICG also showed a weak signal in the tumor lesions due to the enhanced permeability and retention effect, but the intensity decreased quickly within 48 h. Conclusions: The developed GnRHR-targeted imaging agent GnRHa-ICG could specifically detected peritoneal tumor lesions from normal peritoneal and intestines tissues because of the modification of GnRHa to ICG. The plateau period of GnRHa-ICG accumulation may be feasible for clinical applications in fluorescence-guided surgery. Our GnRHR imaging concept may be effective in other hormone-related tumors with upregulated GnRHR expression.
Copyright © 2020 Liu, Zhou, Feng, Pu, Li, Li, Kang, Zhang and Xu.
KEYWORDS:
gonadotropin-releasing hormone receptor; indocyanine green; near-infrared fluorescence; ovarian cancer; targeted imaging
7.
Front Oncol. 2020 Feb 28;10:263. doi: 10.3389/fonc.2020.00263. eCollection 2020.
Serum Immunoglobulin G Is Associated With Decreased Risk of Pancreatic Cancer in the Swedish AMORIS Study.
Sollie S1, Santaolalla A1, Michaud DS2,3, Sarker D1,4, Karagiannis SN5, Josephs DH1,4, Hammar N6, Walldius G7, Garmo H1, Holmberg L1, Jungner I8, Van Hemelrijck M1,6.
Abstract
Background: Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. Experimental studies have reported high expression levels of antigens in pancreatic cancer cells. Therefore, we aimed to investigate the role of different components of humoral immunity in the context of pancreatic cancer. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study. Methods: We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM (n = 41,900, 136,221, and 29,919, respectively). Participants were excluded if they had a history of chronic pancreatitis and individuals were free from pancreatic cancer at baseline. Multivariate Cox proportional hazards regression was used to estimate risk of pancreatic cancer for medical cut-offs of IgA, IgG, and IgM. Results: Compared to the reference level of 6.10-14.99 g/L, risk of pancreatic cancer was elevated among those with IgG levels <6.10 g/L [HR: 1.69 (95% CI 0.99-2.87)], and an inverse association was observed among those with IgG levels ≥15.00 g/L [0.82 (95% CI 0.64-1.05); Ptrend = 0.027]. The association appeared to be stronger for women than men [HR: 0.64 (95% CI 0.43-0.97) and 0.95 (95% CI 0.69-1.29), respectively]. No associations were observed with IgA or IgM. Conclusion: An inverse association was observed between pre-diagnostic serum levels of IgG and risk of pancreatic cancer. Our findings highlight the need to further investigate the role of immune response in pancreatic cancer etiology.
Copyright © 2020 Sollie, Santaolalla, Michaud, Sarker, Karagiannis, Josephs, Hammar, Walldius, Garmo, Holmberg, Jungner and Van Hemelrijck.
KEYWORDS:
AMORIS; IgA; IgG; IgM; immune system and cancer; pancreatic cancer; serum immunoglobulin
8.
Front Oncol. 2020 Feb 28;10:262. doi: 10.3389/fonc.2020.00262. eCollection 2020.
A Bump in the Road: How the Hostile AML Microenvironment Affects CAR T Cell Therapy.
Abstract
Chimeric antigen receptor (CAR) T cells targeting CD19 have been successful treating patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas. However, relapse after CAR T cell therapy is still a challenge. In addition, preclinical and early clinical studies targeting acute myeloid leukemia (AML) have not been as successful. This can be attributed in part to the presence of an AML microenvironment that has a dampening effect on the antitumor activity of CAR T cells. The AML microenvironment includes cellular interactions, soluble environmental factors, and structural components. Suppressive immune cells including myeloid derived suppressor cells and regulatory T cells are known to inhibit T cell function. Environmental factors contributing to T cell exhaustion, including immune checkpoints, anti-inflammatory cytokines, chemokines, and metabolic alterations, impact T cell activity, persistence, and localization. Lastly, structural factors of the bone marrow niche, secondary lymphoid organs, and extramedullary sites provide opportunities for CAR T cell evasion by AML blasts, contributing to treatment resistance and relapse. In this review we discuss the effect of the AML microenvironment on CAR T cell function. We highlight opportunities to enhance CAR T cell efficacy for AML through manipulating, targeting, and evading the anti-inflammatory leukemic microenvironment.
Copyright © 2020 Epperly, Gottschalk and Velasquez.
KEYWORDS:
acute myeloid leukemia; cellular therapy; chimeric antigen receptor; immunotherapy; microenvironment
9.
Front Oncol. 2020 Feb 28;10:256. doi: 10.3389/fonc.2020.00256. eCollection 2020.
Mitochondrial Redox Hubs as Promising Targets for Anticancer Therapy.
Abstract
Mitochondria play multifaceted roles in malignant tumor progression. Beyond their bioenergetic role, mitochondria are essential for providing malignant cells a higher plasticity to face the harsh environmental conditions. Cell-autonomous metabolic deregulation of cancer cells, or metabolic adaptation to microenvironmental cues (lack of nutrients, stromal supply, hypoxia, etc.), represent the triggering event of mitochondria overexploitation to orchestrate nutrient sensing and upload, signaling, and redox circuits. As readout of their higher function, mitochondria produce high amounts of reactive oxygen species (ROS) that are functional for multiple signaling networks underlying tumor proliferation, survival, and metastatic process. To compensate for the higher rate of mitochondrial ROS production, cancer cells have evolved adaptive mechanisms to increase their antioxidant systems and to address ROS activating pathways useful for the tumor cell adaptation to environmental changes. As these properties are critical for cancer progression, mitochondrial ROS have recently become an attractive target for anti-cancer therapies. We discuss how understanding of mitochondrial function in the tumor-specific generation of ROS will impact on the development of novel redox-based targeted therapeutic strategies.
Copyright © 2020 Ippolito, Giannoni, Chiarugi and Parri.
KEYWORDS:
ROS—reactive oxygen species; anti oxidant; anticancer activity; mitochondria; redox targeting; tumor microenviroment
10.
Front Oncol. 2020 Feb 28;10:255. doi: 10.3389/fonc.2020.00255. eCollection 2020.
Stratification of Candidates for Induction Chemotherapy in Stage III-IV Nasopharyngeal Carcinoma: A Large Cohort Study Based on a Comprehensive Prognostic Model.
Abstract
Objective: To establish a prognostic index (PI) for patients with stage III-IV nasopharyngeal carcinoma (NPC) patients to personalize recommendations for induction chemotherapy (IC) before intensity-modulated radiotherapy (IMRT). Patients and Methods: Patients received concurrent chemoradiotherapy (CCRT) with or without IC. Factors used to construct the PI were selected by a multivariate analysis of progression-free survival (PFS), which was the primary endpoint (P < 0.05). Five variables were selected based on a backward procedure in a Cox proportional hazards model: gender, T stage, N stage, lactate dehydrogenase (LDH), and Epstein-Barr virus (EBV) DNA. The cutoff value for the PI was determined by the receiver operating characteristic curve analysis. Results: The present study involved 3,586 patients diagnosed with stage III-IV NPC. The cutoff value for PI was 0.8. The high-risk subgroup showed worse outcomes than did the low-risk subgroup on all endpoints: PFS, overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). In the low-risk subgroup (PI <0.8), patients showed comparable survival outcomes on all clinical endpoints regardless of IC application, whereas in the high-risk subgroup (PI > 0.8), the addition of IC significantly improved PFS, OS, and DMFS, but not LRFS. In multivariate analyses, IC was a protective factor for PFS, OS, and DMFS in the high-risk subgroup, while it had no significant benefit in the low-risk subgroup. Conclusion: The proposed prognostic model effectively stratifies patients with stage III-IV NPC. High-risk patients are candidates for IC before CCRT, while low-risk patients are unlikely to benefit from it.
Copyright © 2020 Sun, Xiao, Lu, Liu, Chen, Yuan, Tang and Mai.
KEYWORDS:
Epstein–Barr virus DNA; induction chemotherapy; nasopharyngeal carcinoma; radiotherapy; survival
11.
Front Oncol. 2020 Feb 28;10:248. doi: 10.3389/fonc.2020.00248. eCollection 2020.
A Contrast-Enhanced Computed Tomography Based Radiomics Approach for Preoperative Differentiation of Pancreatic Cystic Neoplasm Subtypes: A Feasibility Study.
Shen X1, Yang F2, Yang P3,4,5, Yang M2, Xu L3,4, Zhuo J2, Wang J2, Lu D2, Liu Z2, Zheng SS2, Niu T3,4,6, Xu X2.
Abstract
Background: Serous cystadenoma (SCA), mucinous cystadenoma (MCN), and intraductal papillary mucinous neoplasm (IPMN) are three subtypes of pancreatic cystic neoplasm (PCN). Due to the potential of malignant-transforming, patients with MCN and IPMN require radical surgery while patients with SCA need periodic surveillance. However, accurate pre-surgery diagnosis between SCA, MCN, and IPMN remains challenging in the clinic. Methods: This study enrolled 164 patients including 76 with SCA, 40 with MCN and 48 with IPMN. Patients were randomly split into a training cohort (n = 115) and validation cohort (n = 41). We performed statistical analysis and Boruta method to screen significantly distinct clinical factors and radiomics features extracted on pre-surgery contrast-enhanced computed tomography (CECT) images among three subtypes. Three reliable machine-learning algorithms, support vector machine (SVM), random forest (RF) and artificial neural network (ANN), were utilized to construct classifiers based on important radiomics features and clinical parameters. Precision, recall, and F1-score were calculated to assess the performance of the constructed classifiers. Results: Nine of 547 radiomics features and eight clinical factors showed a significant difference among SCA, MCN, and IPMN. Five radiomics features (Histogram_Entropy, Histogram_Skeweness, LLL_GLSZM_GLV, Histogram_Uniformity, HHL_Histogram_Kurtosis), and four clinical factors, including serum carbohydrate antigen 19-9, sex, age, and serum carcinoembryonic antigen, were identified important by Boruta method. The SVM classifier achieved an overall accuracy of 73.04% in training cohort and 71.43% in validation cohort, respectively. The RF classifier achieved overall accuracy of 84.35 and 79.59%, respectively. The constructed ANN model showed an overall accuracy of 77.39% in the training dataset and 71.43% in the validation dataset. All the three classifiers showed high F1 score for differentiation among the three subtypes. Conclusion: Our study proved the feasibility and translational value of CECT-based radiomics classifiers for differentiation among SCA, MCN, and IPMN.
Copyright © 2020 Shen, Yang, Yang, Yang, Xu, Zhuo, Wang, Lu, Liu, Zheng, Niu and Xu.
KEYWORDS:
contrast-enhanced computed tomography; differentiation diagnosis; machine learning; pancreatic cystic neoplasm; radiomics
12.
Front Oncol. 2020 Feb 28;10:245. doi: 10.3389/fonc.2020.00245. eCollection 2020.
Neoadjuvant Treatment in Pancreatic Cancer.
Abstract
Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.
Copyright © 2020 Oba, Ho, Bao, Al-Musawi, Schulick and Chiaro.
KEYWORDS:
FOLFIRINOX; borderline resectable; gemcitabine; locally advanced; nab-paclitaxel; neoadjuvant chemoradiotherapy; neoadjuvant chemotherapy; neoadjuvant therapy
13.
Front Oncol. 2020 Feb 28;10:241. doi: 10.3389/fonc.2020.00241. eCollection 2020.
GLI1 Inhibitor SRI-38832 Attenuates Chemotherapeutic Resistance by Downregulating NBS1 Transcription in BRAFV600E Colorectal Cancer.
Abstract
Resistance to radiation and chemotherapy in colorectal cancer (CRC) patients contribute significantly to refractory disease and disease progression. Herein, we provide mechanistic rationale for acquired or inherent chemotherapeutic resistance to the anti-tumor effects of 5-fluorouracil (5-FU) that is linked to oncogenic GLI1 transcription activity and NBS1 overexpression. Patients with high levels of GLI1 also expressed high levels of NBS1. Non-canonical activation of GLI1 is driven through oncogenic pathways in CRC, like the BRAFV600E mutation. GLI1 was identified as a novel regulator of NBS1 and discovered that by knocking down GLI1 levels in vitro, diminished NBS1 expression, increased DNA damage/apoptosis, and re-sensitization of 5-FU resistant cancer to treatment was observed. Furthermore, a novel GLI1 inhibitor, SRI-38832, which exhibited pharmacokinetic properties suitable for in vivo testing, was identified. GLI1 inhibition in a murine BRAFV600E variant xenograft model of CRC resulted in the same down-regulation of NBS1 observed in vitro as well as significant reduction of tumor growth/burden. GLI1 inhibition could therefore be a therapeutic option for 5-FU resistant and BRAFV600E variant CRC patients.
Copyright © 2020 Zhang, Ma, Avery, Sambandam, Nguyen, Xu, Suto and Boohaker.
KEYWORDS:
5-FU resistance; DNA damage repair; GLI1 target gene; colorectal cancer; novel GLI1 inhibitor; target therapy
14.
Front Oncol. 2020 Feb 28;10:191. doi: 10.3389/fonc.2020.00191. eCollection 2020.
miR-125a Induces HER2 Expression and Sensitivity to Trastuzumab in Triple-Negative Breast Cancer Lines.
Abstract
The EGFR/HER2 signaling network is an effective therapeutic target for HER2-positive cancers, which are known for their aggressive biological course. Evidence indicates that the EGFR/HER2 network plays a role in the aggressive basal-like subtype as well. Here, we studied the potential role of miR-125a-3p as a modulator of the EGFR/HER2 pathway in basal-like breast cancer. Over-expression of miR-125a-3p reduced the migratory capability of MDA-MB-231 cells and led to an increase in the expression of ErbB2 transcript and protein. The induced ErbB2 responded to trastuzumab and underwent internalization and subsequent intra-lysosomal degradation. Trastuzumab treatment further reduced the migratory capability and induced the apoptosis of the cells. An in-vivo mouse model, which supported the in-vitro findings, showed a synergistic effect for miR-125a-3p and trastuzumab. Trastuzumab-treated miR-125a-3p-induced tumors were significantly smaller than control induced tumors. Our findings indicate that, in the basal-like subtype of breast cancer, miR-125a-3p may act as a tumor suppressor. miR-125a-3p induces an increase in the expression of ErbB2 that may render the cells suitable for treatment with anti-HER2 therapies.
Copyright © 2020 Ninio-Many, Hikri, Burg-Golani, Stemmer, Shalgi and Ben-Aharon.
KEYWORDS:
ErbB2; TNBC; apoptosis; epigenetics; miRNA; migration
15.
Front Oncol. 2020 Feb 28;10:171. doi: 10.3389/fonc.2020.00171. eCollection 2020.
Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis.
Abstract
Background: Primary liver cancer is a leading cause of cancer deaths worldwide. Global burden varies, reflecting geographical distribution of viral hepatitis. Our objective was to perform a systematic review and meta-analysis of published current trends in incidence of adult liver cancers and histological types worldwide. Methods: This study used systematic searches of PubMed, Embase, CINAHL, and Web of Science databases for English-language peer-reviewed articles published from 1 January 2008 to 01 September 2019. Inclusion criteria were population-based studies of adult liver cancer patients with quantitative estimates of temporal trends in incidence for liver cancers and/or histological types. For multiple studies from the same geographical area, only the publication that reported the most recent trends for the same cancer type and population subgroup was included. Review was conducted per PRISMA guidelines. Two authors independently extracted data and critically assessed studies. Proposed contributors to observed trends were extracted from included articles. Study-specific estimates of the annual percentage change (APC) in incidence rates with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis models. Heterogeneity was measured using the I 2 statistics and publication bias evaluated using funnel plots and Egger's tests. Results: Overall, 53 studies met the inclusion criteria, of which 31 were included in the meta-analysis. Overall, pooled APC estimates were +0.8 (95% CI -0.3, +2.0) for liver cancers combined, +2.6 (95% CI +1.2, +4.0) for hepatocellular carcinoma (HCC), and +4.3 (95% CI +2.5, +6.1) for intrahepatic cholangiocarcinoma. Subgroup analyses indicated increasing trends for liver cancers (APC +3.2, 95% CI +2.5, +3.9) and HCC (APC +3.6, 95% CI +2.9, +4.4) in the region of North America/Europe/Australia, whereas corresponding trends were decreasing (APC -1.7, 95% CI -2.2, -1.1) and stable (APC -0.7, 95% CI -1.9, +0.5) in Asia, respectively. Conclusions: Incidence is increasing for adult liver cancers and HCC in Western countries, whereas trends are decreasing in the Asian region, although still remaining high. Our findings highlight the importance of viral hepatitis control and lifestyle interventions to reduce global liver cancer burden. Ongoing surveillance is also vital to detect early shifts in incidence trends.
Copyright © 2020 Dasgupta, Henshaw, Youlden, Clark, Aitken and Baade.
KEYWORDS:
hepatocellular carcinoma; incidence; liver cancer; meta-analysis; systematic review; trends
16.
Front Oncol. 2020 Feb 28;10:158. doi: 10.3389/fonc.2020.00158. eCollection 2020.
The Roles of lncRNA in Cutaneous Squamous Cell Carcinoma.
Abstract
Cutaneous squamous cell carcinoma derives from keratinocytes and is the second most common cause of non-melanoma skin cancer. Cutaneous squamous cell carcinoma (cSCC) develops rapidly and is also the leading cause of death in non-melanoma cancers. Lymph node metastasis occurs in 5% of cSCC patients, and some patients may even metastasize to the viscera. Patients with regional lymphatic metastasis or distant metastases have a <20% 10-year survival rate, indicating the substantial challenge in treating advanced and metastatic cSCC. Some lncRNAs have been found to be abnormally overexpressed in many tumor tissues, so that they can be considered as potential new biomarkers or targets that can be used in the diagnosis and treatment of cSCC in the future. In this review, we summarize the role of lncRNA in cutaneous squamous cell carcinoma to make a better understanding of mutations in cSCC and lay the foundation for effective target therapy of cSCC.
Copyright © 2020 Wang, Sun, Wen, Hao, Du, He and Jiang.
KEYWORDS:
ERK1/2; cancer; cutaneous squamous cell carcinoma; lncRNA; skin
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