Journal of Cancer

Our medical research library holds 11 studies published in Journal of Cancer (2011–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 11 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Ivyspring International Publisher
• Published: 2010 to the present, Australia
• Language: English
• ISSN: 1837-9664 (electronic)
• Its record in the NLM Catalog

2020s

• Establishment and bioinformatics analysis of a four-miRNA prognostic signature for pleural mesothelioma. X. Yang, Y. Lin, B. Dong, et al. 2024;15(20):6505-6520. PubMed · Publisher · Free full text

  Abstract

  Objective: Pleural mesothelioma (PM), an uncommon yet highly aggressive malignant neoplasm, has a very poor prognosis with a median survival of less than one year after diagnosis, morbidity and mortality due to PM are on the rise year by year worldwide. Our research aims to utilize molecular characteristics and microRNAs (miRNAs) as a breakthrough in predicting the survival of PM patients, hoping to find a molecular mechanism that can predict the survival of PM patients. Methods: The miRNA expression profiles and corresponding clinical information of patients with PM were obtained from The Cancer Genome Atlas (TCGA) database, a miRNA-based prognostic signature was developed using Cox regression analysis in the training cohort, which was validated in the testing cohort and complete cohort. The association between miRNA levels and survival outcomes was determined, the miRNAs in prognostic model were experimentally validated by quantitative real-time PCR (qRT-PCR) in cell lines. Target genes of prognostic miRNAs were identified using TargetScan, miRDB, and miRTarBase databases, biological function prediction of which was accomplished by GO and KEGG analysis. Gene Expression Omnibus (GEO) database was utilized for core targets recognition, immune infiltration and survival analysis were conducted to investigate the relationship between core targets and immune cells by bioinformatics analysis. Results: This miRNA-related prognostic risk model can effectively stratify patients into high-risk and low-risk groups, and have good sensitivity and specificity to assess the prognosis of patients with PM, which can also be used as an independent prognostic factor for overall survival (OS) prediction in patients with PM, the OS for patients in high-risk group was significantly poorer compared with patients in low-risk group. Moreover, all four miRNAs (hsa-miR-181a-2-3p, hsa-miR-491-5P, hsa-miR-503-5p, and hsa-miR-3934-5p) were found to be differentially expressed in PM cell lines as compared with normal cell line, GO and KEGG analysis revealed that target genes of miRNAs in prognostic model were involved in multiple tumor-associated signaling pathways and functions in PM, core miRNA targets also correlated with immune cell infiltration, indicating their potential role in PM initiation and progression. Conclusions: A robust four-miRNA prognostic signature with great performances in prediction of the OS for PM patients was developed in our study, providing new avenues for the prognostic predication of PM.

  © The author(s).

• From Immunosuppression to Immunomodulation - Turning Cold Tumours into Hot. M. Garofalo, K.W. Pancer, M. Wieczorek, et al. 2022;13(9):2884-2892. PubMed · Publisher · Free full text

  Abstract

  Cancer cells employ various mechanisms to evade and suppress anti-cancer immune responses generating a "cold" immunosuppressive tumour microenvironment. Oncolytic viruses are a promising tool to convert tumour immunosuppression to immunomodulation and improve the efficacy of cancer treatment. Emerging preclinical and clinical findings confirm that oncolytic viruses act in a multimodal scheme, triggering lyses, immunogenic cell death and finally inducing anti-cancer immune responses. In this paper, we tested the local administration of a novel oncolytic adenovirus AdV-D24-ICOSL-CD40L expressing co-stimulatory molecules ICOSL and CD40L to induce the production of tumour infiltrating lymphocytes to the site of injection. Subsequently, in immunocompetent mouse models, we studied possible correlation between tumour infiltrates and anti-cancer efficacy. Described results showed that the delivery of oncolytic viruses encoding immunomodulatory transgenes in combination with anti-PD1 resulted in synergistic inhibition of both melanoma and mesothelioma tumours. Importantly anti-cancer effect positively correlated with cytotoxic CD8+ tumour-infiltrating lymphocytes exerting a central role in the tumour volume control thus generating beneficial outcomes that will undoubtedly provide new insights into possible future treatment strategies to combat cancer. Altogether our findings highlight the importance of oncolytic vectors able to modulate anti-cancer immune responses that can correlate with efficacy in solid malignancies.

  © The author(s).

• Nicotinic-nAChR signaling mediates drug resistance in lung cancer. W.L. Cheng, K.Y. Chen, K.Y. Lee, et al. 2020;11(5):1125-1140. Review PubMed · Publisher · Free full text

  Abstract

  Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking is the most common risk factor for lung carcinoma; other risks include genetic factors and exposure to radon gas, asbestos, secondhand smoke, and air pollution. Nicotine, the primary addictive constituent of cigarettes, contributes to cancer progression through activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated ion channels. Activation of nicotine/nAChR signaling is associated with lung cancer risk and drug resistance. We focused on nAChR pathways activated by nicotine and its downstream signaling involved in regulating apoptotic factors of mitochondria and drug resistance in lung cancer. Increasing evidence suggests that several sirtuins play a critical role in multiple aspects of cancer drug resistance. Thus, understanding the consequences of crosstalk between nicotine/nAChRs and sirtuin signaling pathways in the regulation of drug resistance could be a critical implication for cancer therapy.

  © The author(s).

• Sex Differences and Adverse Effects between Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer. T. Tsiouda, C. Sardeli, K. Porpodis, et al. 2020;11(11):3407-3415. PubMed · Publisher · Free full text

  Abstract

  Introduction: Lung cancer remains the leading cause of cancer mortality in men and women and around the world. Approximately 90% of cases of lung cancer are caused by smoking and the use of tobacco products. However, other factors such as asbestos, air pollution and chronic infections can contribute to pulmonary carcinogenesis. Lung cancer is divided into two broad histological categories, which develop and spread different small cell lung carcinomas and non-small cell lung carcinomas. The treatment options for lung cancer include surgery, radiotherapy, chemotherapy and targeted treatments. Tumor induced immune suppression is vital for malignant progression. Immunotherapies act by strengthening the patient's innate tendency for an immune response and give positive promise to patients with non-small cell lung cancer and small cell lung cancer. Immune checkpoint inhibitors are a new approach to cancer therapies. Just as immune therapies include a new approach to cancer biology, the toxicities associated with these factors have created new challenges in clinical practice. Materials & Methods: Patients (218) aged 40-80 years were treated with either chemotherapy or immunotherapy. Their response to treatment and any subsequent adverse drug reactions were studied. Results: 69% of patients were treated with chemotherapy and 31% were treated with immunotherapy. The type of treatment had a statistically significant effect on the undesirable effects of the treatment. Conclusions: The type of treatment was statistically significant in responding to the treatment and treatment side effects but not in the rate of death.

  © The author(s).

2010s

• An Integrated Analysis of the Genome-Wide Profiles of DNA Methylation and mRNA Expression Defining the Side Population of a Human Malignant Mesothelioma Cell Line. M.C. Kim, N.Y. Kim, Y.R. Seo, et al. 2016;7(12):1668-1679. PubMed · Publisher · Free full text

  Abstract

  Intratumoral heterogeneity is a hallmark of all cancers and functions as the major barrier against effective cancer therapy. In contrast to genetic mutations, the role of epigenetic modifications in the generation and maintenance of heterogeneous cancer cells remains largely undetermined. This study was performed to evaluate the epigenetic mechanisms involved in the tumor cell heterogeneity using side population (SP) and non-SP cells isolated from a human malignant mesothelioma (HMM) cell line. The subpopulations of cancer cells were analyzed by methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) and RNA-seq methodology. The RNA-seq data were analyzed with the MeDIP-seq data in an integrated way to identify the epigenetically modified genes that defined the SP. Concomitant changes in mRNA expression and DNA methylation were found in 122 genes, including 118 down-regulated genes with hypermethylation and 4 up-regulated genes with hypomethylation. Gene ontology revealed that a large portion of the genes belonged to the groups of biological processes such as stem cell maintenance, stem cell development, stem cell differentiation, and the negative regulation of the developmental process. Among these genes, BNC1, RPS6KA3, TWSG1 and DUSP15 contained aberrant methylation in the CpG islands of the promoter region, indicating that the genes regulated by DNA methylation characterized a distinct subpopulation of HMM cells. The present study provided valuable information to shed light on the epigenetic contributions to the generation and maintenance of tumor cell heterogeneity.

• Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy. R.F. Walter, C. Vollbrecht, R. Werner, et al. 2016;7(13):1915-1925. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown.

  Material And Methods: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment.

  Results: CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73 expression was associated with progression in this subgroup.

  Conclusion: DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management.

• FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy. G. Genestreti, A. Moretti, S. Piciucchi, et al. 2012;3:241-5. PubMed · Publisher · Free full text

  Abstract

  Purpose: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy.

  Methods: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq (18)F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM) iterative reconstruction algorithm.

  Results: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic), with a median age of 65 years (range: 54-77), were evaluated. Median follow-up was 31 months (range: 4-44). After TP treatment, there was a mean interval of 14 days (range: 9-22) and 125 days (range: 76-162) between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75%) and 3 (37.5%) patients, respectively.

  Conclusion: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax.

• Telomerase-independent paths to immortality in predictable cancer subtypes. S.T. Durant. 2012;3:67-82. PubMed · Publisher · Free full text

  Abstract

  The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT). ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR) components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour) and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets.

• HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy. X. Xiang, M. Feng, M. Felder, et al. 2011;2:280-91. PubMed · Publisher · Free full text

  Abstract

  Background: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin.

  Methodology/Principal Findings: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB) and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 µg/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro.

  Conclusion/Significance: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant immunoadhesins can have advantages usually found in monoclonal antibodies such as ease of purification, high binding affinity and effector functions.

• In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice. M. Feng, J. Zhang, M. Anver, et al. 2011;2:123-31. PubMed · Publisher · Free full text

  Abstract

  Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

• Rapid generation of in vitro multicellular spheroids for the study of monoclonal antibody therapy. Y.T. Phung, D. Barbone, V.C. Broaddus, et al. 2011;2:507-14. PubMed · Publisher · Free full text

  Abstract

  Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellular spheroids, a simple and more relevant model of in vivo tumors that allows for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. The protocol is used to produce in vitro three-dimensional tumor spheroids from established human cancer cell lines and primary cancer cells isolated from patients without the use of any extracellular components. To study the ability of tumor-targeting immunoconjugates to penetrate these tumor spheroids in vitro, we have used an immunotoxin targeting mesothelin, a surface protein expressed in malignant mesotheliomas. This method for producing consistent, reproducible 3D spheroids may allow for improved testing of novel monoclonal antibodies and other agents for their ability to penetrate solid tumors for cancer therapy.

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