Anticancer Research

Our medical research library holds 27 studies published in Anticancer Research (2005–2023). 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. 27 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: International Institute of Anticancer Research
• Published: 1981 to the present, Greece
• Language: English
• ISSN: 0250-7005 (print), 1791-7530 (electronic)
• Its record in the NLM Catalog

2020s

• FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling. I. Endo, V.J. Amatya, K. Kushitani, et al. 2023;43(9):3961-3968. PubMed · Publisher

  Abstract

  Background/Aim: Forkhead box M1 (FOXM1) is a transcription factor closely associated with various human malignancies and is considered an attractive target for cancer therapy. Mesothelioma is a malignancy primarily due to asbestos exposure and certain genetic factors, requiring a better understanding of tumorigenesis for improved treatment. Asbestos-exposed human mesothelial cells have been reported to up-regulate FOXM1 expression in a dose-dependent manner.

  Materials And Methods: FOXM1 expression was evaluated in mesothelioma tissues and cell lines. FOXM1 small interfering RNA was transfected into mesothelioma cell lines to analyze its biological functions and regulatory mechanisms.

  Results: FOXM1 was over-expressed in mesothelioma tissues and cell lines. Knock-down of FOXM1 in mesothelioma cell lines inhibited cell proliferation, migration, and invasion. These results suggest that up-regulation of FOXM1 expression promotes mesothelioma tumorigenesis and progression. We previously reported that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes the proliferation, migration, and invasion of mesothelioma cell lines. In this study, IGF2BP3 knock-down suppressed FOXM1 expression in mesothelioma cell lines. Our results suggest that IGF2BP3, an upstream regulator, contributes to increased FOXM1 expression. Furthermore, IGF2BP3 and FOXM1 knock-down suppressed SMAD signaling by inhibiting SMAD2/3 phosphorylation in mesothelioma cell lines.

  Conclusion: IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment.

  Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• ADAR2 Regulates Malignant Behaviour of Mesothelioma Cells Independent of RNA-editing Activity. K.I. Sakata, K. Maeda, N. Sakurai, et al. 2020;40(3):1307-1314. PubMed · Publisher

  Abstract

  Background/Aim: Malignant pleural mesothelioma (MPM) is an intractable cancer, and causes of its malignant transformation are not well known. Adenosine deaminase acting on RNA (ADAR) is an RNA-editing enzyme that converts adenosine into inosine in double-stranded RNAs potentially involved in malignant development.

  Materials And Methods: To examine the role of ADAR1 and ADAR2 in MPM, small interfering RNAs (siRNAs) against ADAR1 or ADAR2 were used.

  Results: Transfection of siRNA against ADAR2 suppressed proliferation, motility, and invasiveness of MPM cells expressing both ADAR1 and ADAR2; however, siRNA against ADAR1 did not affect these cellular activities. Overexpression of ADAR2, that was incapable of binding to RNA, suppressed growth, motility, and invasion of MPM cells. However, overexpression of ADAR2 that had no enzyme activity did not alter the malignant properties of MPM cells.

  Conclusion: Enhancement of the malignant characteristics of cultured MPM cells via ADAR2 was independent of RNA-editing activity.

  Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Hypoxia Inducible Factor-1α Inhibition in Von Hippel Lindau-mutant Malignant Pleural Mesothelioma Cells. T. Shukuya, J. Oyanagi, M. Serizawa, et al. 2020;40(4):1867-1874. PubMed · Publisher

  Abstract

  Background/Aim: Molecular targeted agents have been successfully developed against solid tumors and their use is also being investigated for the treatment of malignant pleural mesothelioma (MPM). We have previously reported von Hippel Lindau (VHL) mutations detected by massive parallel sequencing technology in samples of patients with MPM. Here, we conducted an in vitro study to investigate the therapeutic approaches in VHL-mutant MPM.

  Materials And Methods: Three MPM cell lines with or without a VHL mutation were used and the effects of molecular-targeted agents on growth inhibition were evaluated. Based on the characteristics of the molecular targeted agents that exhibited growth inhibitory effect, the effects of knockdown by siRNA were also evaluated.

  Results: NCI-H28 MPM cells harboring the VHL L89H mutation were sensitive to YC-1, known as an inhibitor of hypoxia inducible factor (HIF)-1α, and YC-1treatment induced massive apoptosis in a dose-and-time-dependent manner. Knockdown of HIF-1α by siRNA partially inhibited the growth of NCI-H28 cells, suggesting that an additional blockade may be required to completely inhibit growth signaling.

  Conclusion: The VHL mutation may predict tumor responses to YC-1, a HIF-1α inhibitor.

  Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• New Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modulation of the Human Equilibrative Nucleoside Transporter-1 in Peritoneal Mesothelioma. G. Li Petri, C. Pecoraro, O. Randazzo, et al. 2020;40(9):4913-4919. PubMed · Publisher

  Abstract

  Background/Aim: A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease.

  Materials And Methods: Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells.

  Results: Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 μM in both cell lines growing as monolayers or as spheroids. Their antiproliferative and antimigratory activity was associated with inhibition of phospho-FAK, as detected by a specific ELISA assay in STO cells. Interestingly, these compounds potentiated the antiproliferative activity of gemcitabine, and these results might be explained by the increase in the mRNA expression of the key gemcitabine transporter human equilibrative nucleoside transporter-1 (hENT-1).

  Conclusion: These promising results support further studies on new imidazo[2,1-b][1,3,4]thiadiazole compounds as well as on the role of both FAK and hENT-1 modulation in order to develop new drug combinations for peritoneal mesothelioma.

  Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

2010s

• 2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth. I. Gerogianni, E. Pitaraki, R.M. Jagirdar, et al. 2019;39(7):3809-3814. PubMed · Publisher

  Abstract

  Background/Aim: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy.

  Materials And Methods: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested.

  Results: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types.

  Conclusion: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.

  Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Malignant Peritoneal Mesothelioma: Treatment Options and Survival. S.A.S. Salo, I. Ilonen, S. Laaksonen, et al. 2019;39(2):839-845. PubMed · Publisher

  Abstract

  Background: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.

  Materials And Methods: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.

  Results: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).

  Conclusion: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.

  Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Tenascin XB Is a Novel Diagnostic Marker for Malignant Mesothelioma. K. Nakayama, M. Seike, R. Noro, et al. 2019;39(2):627-633. PubMed · Publisher

  Abstract

  Background/Aim: Malignant mesothelioma (MM) is an aggressive tumor with poor prognosis. The establishment of a new diagnostic and therapeutic approach for MM is expected. This study investigated the diagnostic significance of tenascin XB (TNXB) for MM.

  Materials And Methods: TNXB gene expression was found to be significantly higher in MM tumor tissues compared to paired normal tissues, as assessed by the Gene Expression Omnibus database. The inhibition of TNXB using small interfering RNAs suppressed the proliferation and colony formation of MM cells. Expression of TNXB and calretinin, a current diagnostic marker of MM, was evaluated by immunohistochemistry.

  Results: The sensitivity and specificity of TNXB for MM were 80.0% and 69.5%, respectively. When the detection of TNXB was combined with that of calretinin, 83.3% of MM cases were detected.

  Conclusion: These findings suggest that TNXB is a novel diagnostic biomarker for MM. A combination of detecting TNXB and calretinin may be useful for the differential diagnosis of MM from lung adenocarcinoma.

  Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• The mTOR Signaling Pathway Is Associated With the Prognosis of Malignant Pleural Mesothelioma After Multimodality Therapy. A. Kuroda, S. Matsumoto, A. Fukuda, et al. 2019;39(11):6241-6247. PubMed · Publisher

  Abstract

  Background/Aim: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment.

  Patients And Methods: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP).

  Results: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate.

  Conclusion: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.

  Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy. B. Singh, G. Singh, M. Pourgholami, et al. 2018;38(10):5917-5921. PubMed · Publisher

  Abstract

  Background/Aim: To assess the impact of short- and long-term outcomes of bilateral vs. unilateral diaphragm interventions in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC).

  Patients And Methods: A total of 652 CRS/IPC procedures, between 1996 and 2018, required diaphragm interventions. Among these, 388 underwent bilateral intervention. Preoperative heterogeneity was assessed in 6 parameters and addressed with propensity score matching. The association of each respective analysis was assessed with 11 outcomes. Overall survival was assessed based on histology.

  Results: CRS/IPC requiring bilateral diaphragmatic interventions illustrated significantly increased operative hours (9.6 vs. 8.6 hours, p<0.001). Postoperatively, there was significantly increased red blood cell (RBC) transfusion (6.37 units vs. 4.47 units, p=0.007) and grade III and IV complications (57.3% vs. 40.6%, p=0.004). No difference was noted in ICU stay, total length of stay, hospital death and return to OT. In terms of respiratory complications, an increased incidence of pneumothorax (16.5% vs. 6.2%, p<0.001) was noted whilst pleural effusions and pneumonia occurrences were non-significant. Overall survival, revealed bilateral interventions in low-grade appendiceal mucinous neoplasm conferred an increased relative risk (p=0.037, RR=2.230, 95%CI=1.052-4.730). They did not have an effect on OS in colorectal cancer and mesothelioma.

  Conclusion: Despite the increase in short-term morbidity, bilateral diaphragm interventions resulted in similar long-term survival to unilateral interventions.

  Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• A Case of the Resected Lymphohistiocytoid Mesothelioma: BAP1 Is a Key of Accurate Diagnosis. T. Matsubara, G. Toyokawa, Y. Yamada, et al. 2017;37(12):6937-6941. Case report PubMed · Publisher

  Abstract

  Background: Malignant mesothelioma (MM) is a well-known malignant tumor that occurs in the pleura and is histopathologically classified into three subtypes. Lymphohistiocytoid mesothelioma (LHM) is considered a variant of epithelioid MM, and few cases have been reported. First case of LHM was reported by Henderson et al. in 1988. It is difficult to precisely diagnose LHM, and it is often misdiagnosed as reactive mesothelial cell proliferation.

  Case Report: An 82-year-old man, with the smoking history of nine pack-years, was referred to our Department due to an abnormal shadow and pleural effusion in the left lung field on the chest X-ray imaging. His occupation was a teacher through his life without any asbestos exposure. Computed tomography (CT) and 18F-fluorodeoxyglucose-position emission tomography showed a tumor which was suggestive of malignancy on the left chest wall, with the possible invasion into the left 2nd to 4th ribs. He underwent a CT-guided biopsy and a thoracentesis, but the tumor was shown to be a benign tumor indicative of a reactive mesothelial cell proliferation. Then, he underwent a surgical resection and the tumor was suspected of liposarcoma macroscopically. Histological and immunohistochemical findings were suggestive of mesothelial lesion, such as nodular histiocytic or mesothelial hyperplasia. However, loss of BAP1 and no p16 homozygous deletion in the tumor cells led to the diagnosis of LHM, not a benign lesion.

  Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Puzzling Results from BAP1 Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy. C. Rizzardi, E. Athanasakis, F. Cammisuli, et al. 2017;37(6):3073-3083. PubMed · Publisher

  Abstract

  Background: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.

  Materials And Methods: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.

  Results: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%).

  Conclusion: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.

  Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

• Computed Tomographic Features of Malignant Peritoneal Mesothelioma. K. Kato, K. Gemba, N. Fujimoto, et al. 2016;36(3):1067-72. PubMed

  Abstract

  Aim: The objective of this study was to determine the computed tomographic (CT) features of malignant peritoneal mesothelioma (MPM).

  Patients And Methods: We analyzed CT features of MPM cases and compared them to those of other malignant conditions (non-MPM).

  Results: Multiple nodular lesions occurred more frequently in the MPM group compared to non-MPM cases (p=0.013). Thickening of the mesentery was detected more frequently in MPM cases than in non-MPM cases (56% vs. 18%, p=0.029). Pleural plaques were detected in 13 cases (45%) in the MPM group but were not detected in the non-MPM group. The MPM-CT index score, determined in each case as the sum of the findings which are potentially characteristic of MPM, was significantly higher in MPM than in non-MPM cases (p=0.001).

  Conclusion: MPM presented characteristic CT findings, and the MPM-CT index may be useful for differential diagnosis of MPM.

  Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

• Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma. M. Sasai, H. Nakamura, N. Sougawa, et al. 2016;36(3):907-11. PubMed

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells.

  Materials And Methods: In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model.

  Results: HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT.

  Conclusion: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM.

  Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

• Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells. C.J. Jennings, N. Zainal, I.M. Dahlan, et al. 2016;36(11):5905-5913. PubMed · Publisher

  Abstract

  Introduction: Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.

  Materials And Methods: We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines.

  Results: Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling.

  Conclusion: The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.

  Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

• Status of Anaplastic Lymphoma Kinase (ALK) in malignant mesothelioma. S. Varesano, C. Leo, S. Boccardo, et al. 2014;34(5):2589-92. PubMed

  Abstract

  Background: Malignant mesothelioma (MM) is a particularly aggressive type of primary tumor, associated with exposure to asbestos, and characterized by high mortality. To date, there is no curative therapy for MM. The receptor anaplastic lymphoma kinase (ALK) was found to be mutated in many cases of cancer and used as a target in biological therapies. We investigated whether this pharmacological treatment could also be applicable to MM.

  Materials And Methods: The state of ALK was analyzed by immunohistochemistry and fluorescent in situ hybridization in 63 MM tissue specimens.

  Results: None of the 63 MM samples showed overexpression or translocation of ALK.

  Conclusion: Our preliminary data exclude the utility of analysis of the ALK gene in MM and suggest that ALK inhibitor therapy is not applicable to MM.

• Up-regulation of DDX39 in human malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells. Y. Kuramitsu, W. Tominaga, B. Baron, et al. 2013;33(6):2557-60. PubMed

  Abstract

  Malignant pleural mesothelioma (MPM) is a malignant tumor originating from mesothelial cells existing in pleura. Since its incidence, it is closely related to the amount and time of exposure to asbestos, and the latency period after exposure to asbestos is very long, the incidence may increase over the next two decades. Since early detection is very difficult and there is no standard curative therapy, it is important to understand the biology of MPM, and to find biomarkers and molecular targets for its therapy. DDX39 is one of the Asp-Glu-Ala-Asp (DEAD)-box RNA helicases, which are required for the export of mRNA out of the nucleus, and transcription, splicing and transport of mRNA. Some reports have shown differential expression of DDX39 in tumor cells or tissues such as lung squamous cell cancer, gastrointestinal stromal tumor and urinary bladder cancer. In the present study, the protein levels of DDX39 in the human MPM cell lines NCI-H28, NCI-H2052 and NCI-H2452, and the human pleural mesothelial cell line MeT-5A were investigated by western blotting. The protein levels of DDX39 were found to be higher in NCI-H28, NCI-H2052 and NCI-H2452 compared to MeT-5A. The intensity of the bands of DDX39 in NCI-H28, NCI-H2052 and NCI-H2452 cells were increased by 1.351-, 1.887- and 2.024-fold, respectively, compared to MPM cells. These results suggest that DDX39 is a possible candidate biomarker for molecular-targeting of MPM.

• YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis. M. Corradi, M. Goldoni, R. Alinovi, et al. 2013;33(12):5517-24. PubMed

  Abstract

  Background/Aim: In the diagnosis of malignant mesothelioma (MM) there still is a lack of specific and sensitive screening biomarkers: this study examined the discriminatory power of a panel of serum/plasma biomarkers.

  Patients And Methods: The study involved four groups: (a) individuals previously exposed to asbestos with asbestosis; (b) patients with MM; (c) patients with non-small cell lung cancer; and (d) controls without any evidence of malignancy. The concentrations of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients were determined.

  Results: Patients with MM had significantly higher serum levels of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167 pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels improved diagnostic specificity.

  Conclusion: The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.

• Chemoprevention of asbestos-linked cancers: a systematic review. M. Neri, D. Ugolini, S. Boccia, et al. 2012;32(3):1005-13. Systematic review PubMed

  Abstract

  Asbestos has been used extensively and, in spite of many countries having banned most of its uses, professional, domestic and environmental exposure has not ceased worldwide. Inhaled asbestos fibers can lead to malignant mesothelioma, lung cancer and non-cancerous conditions, while the substance persists indefinitely in the lung and pleural tissue, resulting in continuous damage. Exposed individuals may be offered medical surveillance or compensation, but nothing is currently being done to lower their specific cancer risk: chemoprevention seems a promising approach. A web search and a PubMed review of the literature on chemoprevention trials in individuals exposed to asbestos have been conducted. Forty-six articles on five projects were found and newly reviewed but, surprisingly, no novel trials have been set up for twenty years, although considerable advances have been gained in cancer chemoprevention. A re-consideration of possibilities offered by chemoprevention should be encouraged. New trials based on the most recently characterized molecules should be planned, taking into account specific issues such as the need for a very large number of participants and a long follow up or, alternatively, the use of biomarkers as surrogate endpoints. The long latency of asbestos related diseases may offer delayed intervention opportunities. The lack of chemoprevention trials for asbestos exposure highlights the urgent need for research in this field.

• Detection of human papillomavirus genotypes in bronchial cancer using sensitive multimetrix assay. K. Syrjänen, M. Silvoniemi, E. Salminen, et al. 2012;32(2):625-31. PubMed

  Abstract

  Background: Since first suggested in 1979, evidence on the involvement of human papillomavirus (HPV) in bronchial carcinogenesis has been accumulated through several lines of research. The causal role of HPV in lung cancer still remains controversial, however, and more data are needed particularly on genotype distribution and cofactors of HPV regarding this disease.

  Materials And Methods: The present series consists of 77 patients diagnosed and treated for lung cancer at the Department of Respiratory Medicine, Turku University Hospital, (Finland) during 2008-2010. All available histological samples (n=77) were subjected to HPV genotyping with the Luminex-based Multimetrix kit, detecting 24 low-risk (LR) and high-risk (HR) HPV types. Pertinent clinical data were collected and subjected to univariate and multivariate regression analysis to disclose the covariates associated with HPV detection in lung cancer.

  Results: Out of 77 histological samples analyzed, four (5.2%) (three squamous cell and one adenocarcinoma) were found to be HPV-positive, out of which three were HPV16 infections and one a double-infection with HPV6 and HPV16. All four patients were males, and all but one reported no asbestos exposure. Three of them had refrained from smoking for a period >22 years. Disease-specific survival was twice as long for individuals with HPV+ than those with HPV- tumors (25.5 vs. 12.8 months), but confounding by treatment cannot be excluded. In univariate analysis, four covariates were significantly associated with HPV detection: i) older age (p=0.003) ii) older age at smoking initiation (p=0.027), iii) fewer years of active smoking (p=0.036), and iv) fewer total pack years (p=0.002). In a multivariate regression model adjusted to all significant covariates, only absolute age was significantly associated with testing as HPV-positive (odds ratio=1.16, 95% confidence interval 1.04-1.39, p=0.008).

  Conclusion: Given the fact that initiation of smoking at an older age, fewer pack years and long smoking abstinence were associated with HPV, it is tempting to speculate that oncogenic HPV can substitute smoking as a risk factor, leading to lung cancer in these patients despite >22 years elapsing since their smoking cessation. In the era of prophylactic HPV vaccination, there is an urgent need to provide more data on the global HPV burden and covariates of the virus associated to lung cancer.

• Loss of mesothelin expression by mesothelioma cells grown in vitro determines sensitivity to anti-mesothelin immunotoxin SS1P. J. Zhang, S. Qiu, Y. Zhang, et al. 2012;32(12):5151-8. PubMed · Free full text

  Abstract

  Background/Aim: To determine if early passage tumor cells obtained from patients with mesothelioma continue to express the tumor differentiation antigen mesothelin and their sensitivity to the anti-mesothelin immunotoxin SS1P.

  Materials And Methods: Cell cultures were established from ascites or pleural effusion of 6 peritoneal and 3 pleural mesothelioma patients, respectively. These cells were evaluated for mesothelin expression by immunohistochemistry and flow cytometry.

  Results: Although mesothelin was highly expressed in tumor biopsies of all patients, only 3 out of 9 malignant effusions from these patients when grown in short-term culture showed strong mesothelin positivity by IHC. By flow cytometry, the number of mesothelin sites per cell was variable ranging from 580 to 210,000 sites/cell. Cells with strong mesothelin expression by IHC and increased number of mesothelin sites/cell were sensitive to SS1P.

  Conclusions: Most mesothelioma tumors loose mesothelin when grown in vitro and the sensitivity of these cells to SS1P is dependent on the number of mesothelin sites/cell.

• Identification of a tumour associated antigen in lung cancer patients with asbestos exposure. M. Yasuda, T. Hanagiri, Y. Shigematsu, et al. 2010;30(7):2631-9. PubMed

  Abstract

  Background: This study analysed the humoral immune response in asbestos exposed lung cancer patients to identify new surrogate markers of the carcinogenic risk in populations exposed to asbestos.

  Methods And Results: A serological analysis identified five distinct antigens reactive with IgG derived from a lung cancer patient with high asbestos exposure. In one of the isolated antigens, quantitative RT-PCR indicated that annexin A2 (AnxA2) was overexpressed in lung cancer tissues and normal lung from patients with high asbestos exposure. Antibody against AnxA2 was detected in 9/15 (60%) of lung cancer patients with high asbestos exposure; however, in only 1/12 (8%) of lung cancer patients with low asbestos exposure. AnxA2 was also overexpressed in malignant mesothelioma cells, and the antibody was also positive in 8/15 (53%) of patients with malignant mesothelioma.

  Conclusion: The antibody titer against AnxA2 may be a potentially useful new diagnostic surrogate marker for asbestos-related lung cancer and malignant mesothelioma.

• Primary pericardial mesothelioma in an asbestos-exposed patient with previous heart surgery. C. Rizzardi, E. Barresi, A. Brollo, et al. 2010;30(4):1323-5. Case report PubMed

  Abstract

  We present a case of primary pericardial mesothelioma occurring in an asbestos-exposed 67-year-old man who underwent four aortocoronary bypass grafting seven years prior to the onset of the mesothelioma. Primary pericardial mesothelioma is a rare tumor whose association with asbestos is more infrequent than that of the much more common pleural form. Factors other than asbestos that may play a role include genetic predisposition, immune impairment, infections, radiation, dietary factors, and recurrent serosal inflammation. We consider that, in the presented case, inflammation and healing resulting from pericardiotomy might have had a synergistic effect with asbestos in the pathogenesis of the tumor. To our knowledge, this is the first reported case of primary pericardial mesothelioma arising in a patient exposed to asbestos who previously underwent cardiac surgery.

• SDF1/CXCL12 is involved in recruitment of stem-like progenitor cells to orthotopic murine malignant mesothelioma spheroids. B.W. Lau, A.B. Kane. 2010;30(6):2153-60. PubMed · Free full text

  Abstract

  Background/Aim: Tumor progression is influenced by the microenvironment. We found stem cells are recruited to malignant mesothelioma spheroids. We aimed to determine if stem cell recruitment depends on the chemokine SDF1, and if inhibition of the cognate receptor CXCR4 affects tumor growth.

  Materials And Methods: The kinetics of stem cell recruitment was determined using immunofluorescence staining, BrdU incorporation and eGFP transgenic mice. Chemokines were identified using PCR array. Inhibitors of CXCR4 were used to determine the effect on cell migration and tumor progression.

  Results: The increasing number of stem cells found in tumor spheroids over time is attributed to cell recruitment. Stem cell migration in vitro was enhanced by exogenous SDF1 and abrogated by CXCR4 inhibition and. CXCR4 inhibition reduced tumor burden in vivo.

  Conclusion: SDF1 is a candidate chemokine for recruitment of stem cells to malignant peritoneal mesothelioma and a potential target for therapy.

2000s

• Malignant mesothelioma of the tunica vaginalis testis in a petrochemical worker exposed to asbestos. S.M. Candura, A. Canto, A. Amatu, et al. 2008;28(2B):1365-8. Case report PubMed

  Abstract

  Malignant mesothelioma of the tunica vaginalis testis is a rare and aggressive asbestos-related malignancy that may pose difficult diagnostic problems. After 16 years of asbestos exposure, a 38-year-old petrochemical worker came to our notice with acute right testicular pain and swelling, simulating torsion of the spermatic cord. Histopathology of surgical samples of the tunica vaginalis revealed tubulopapillary, epithelioid neoplastic proliferation. Immunohistochemical staining for the epithelial glycoprotein Ber-EP4 was negative, whereas results were positive for mesothelial markers, thus leading to the diagnosis of epithelial mesothelioma. The tumour infiltrated the testicular surface and the epididymis, but no distant metastases were found. The patient was treated with radical inguinal orchidectomy without adjuvant therapy and is free from disease 15 months after diagnosis. Tunical mesothelioma may simulate metastatic carcinoma at routine histopathological examination. Immunohistochemistry and occupational anamnesis are helpful for the correct diagnosis, which, in turn, is important for prognosis and treatment, and in relation to legal issues when asbestos is involved in the causation of the disease.

• Human papillomavirus infections in lung cancer. Detection of E6 and E7 transcripts and review of the literature. L. Giuliani, C. Favalli, K. Syrjanen, et al. 2007;27(4C):2697-704. Review PubMed

  Abstract

  Lung cancer is the leading cause of cancer related death in Western countries. Several factors have been implicated in its aetiology: cigarette smoking, environmental pollution, asbestos and genetic factors. The possible involvement of human papillomavirus (HPV) in bronchial squamous cell lesions was first suggested in 1979 by Syrjänen. Since then, several studies have confirmed the presence of HPV DNA in about 20% of lung cancer cases examined, with HPV16 and 18 as the two most frequently found oncogenic viral types. More recently, these data have been supported by the detection of E6 and E7 transcripts in HPV-positive lung cancer cases, reinforcing the hypothesis that oncogenic HPVs could act as cofactors in bronchial carcinogenesis. This published literature is briefly reviewed and new data of the authors on detection of E6 and E7 transcripts in lung cancer samples are presented.

• Cytological value of sputum in workers daily exposed to air pollution. M. Alderisio, M. Cenci, P. Mudu, et al. 2006;26(1A):395-403. PubMed

  Abstract

  In this study, quantitative modifications of dust cells, siderocytes, Curschmann's spirals and asbestos bodies and qualitative modifications (cellular changes and inflammatory infiltrate) in the sputum of 164 traffic police officers and 218 railway workers, occupationally exposed to environmental pollution, and the sputum of 119 inhabitants of a rural area, were evaluated. The results were correlated with time of exposure and smoking habits. Seventy-three (45%) traffic police officers (TPO), 76 (35%) railway workers (RW) and 29 (24%) of the rural population (RP) were smokers. The sputum, collected over a 3-day period, was smeared on glass slides and stained according to the Papanicolaou, Perl and yellow eosin methods. The results of the qualitative cytological diagnosis revealed a statistically significant difference between the TPO, RW and the RP (p < 0.001). The results of the qualitative and quantitative cytological examinations were not significantly correlated to time of occupational exposure, which was considered to be a continuous variable. The qualitative cytological examination of sputa was not statistically significant for the smoking habits of the TPO and the RP, but was significant for the RW (p < 0.0067). In the TPO, the number of dust cells was higher in smokers, and the relative risk (RR) was 3.95. In the RW, the RR was 2.84. The results of our study revealed that for the RW, the qualitative-quantitative cytological alterations in sputum were due much more to smoking habits than to occupational exposure, while the presence of asbestos bodies correlated with work activity. The qualitative-quantitative cytological examinations of the TPO differed significantly from that of the other two populations.

• Development of malignant mesothelioma during treatment for prolymphocytic leukemia: is asbestos or simian virus 40 a link?. T. Tanvetyanon, A.G. Elmishad, M. Carbone. 2005;25(1B):429-33. Case report PubMed

  Abstract

  A patient with a history of heavy asbestos exposure presented with B-prolymphocytic leukemia/lymphoma (B-PLL). Soon after, he developed rapidly progressing malignant peritoneal mesothelioma. The concurrent development of both relatively uncommon diseases raised the possibility that a common causative factor might exist. Since asbestos, simian virus 40 (SV40), or both have been associated with lymphoproliferative disease and mesothelioma, we investigated both possible links in our patient. Imaging studies provided evidence for asbestos exposure because bilateral pleural plaques were identified. Tissues from bone marrow (involved with B-PLL) and from a peritoneal nodule (involved with mesothelioma) were examined for SV40 DNA using polymerase chain reaction (PCR): no SV40 DNA was detected. We conclude that asbestos remains the sole possible connection to both malignancies in this patient. It seems possible that fludarabine, an immunosuppressive chemotherapy, accelerated the occurrence and progression of malignant mesothelioma during the therapy for his B-PLL.

Browse every journal in the library or the library by type of article, or return to medical research.