Journal of Cancer Research and Clinical Oncology

Our medical research library holds 17 studies published in Journal of Cancer Research and Clinical Oncology (1998–2024). 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. 17 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Springer-Verlag
• Published: 1979 to the present, Germany
• Language: English, German
• ISSN: 0171-5216 (print), 1432-1335 (electronic)
• Continues: Zeitschrift Für Krebsforschung und Klinische Onkologie
• Its record in the NLM Catalog

2020s

• BAP1, Wilms' tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma. T.H. Yuce, G. Ak, S. Metintas, et al. 2024;150(2):38. PubMed · Publisher · Free full text

  Abstract

  Purpose: There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.

  Methods: The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.

  Results: Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.

  Conclusions: The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.

  © 2024. The Author(s).

• Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019. Z. Chen, Y. Cai, T. Ou, et al. 2024;150(5):282. PubMed · Publisher · Free full text

  Abstract

  Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.

  © 2024. The Author(s).

• Genetic analysis of familial predisposition in the pathogenesis of malignant pleural mesothelioma. M. Akarsu, G. Ak, E. Dündar, et al. 2023;149(10):7767-7778. PubMed · Publisher · Free full text

  Abstract

  Purpose: Mesothelioma is the primary tumor of the mesothelial cell membrane. The most important etiology is asbestos exposure. The development of malignant mesothelioma in very few of the population exposed to asbestos and its frequent occurrence in some families may be significant in terms of genetic predisposition. Again, the presence of relatives with mesothelioma who did not have asbestos contact strengthens this argument. This disease, which has limited treatment options and has a poor prognosis, revealing a genetic predisposition, if any, may prolong survival with early diagnosis and effective treatment.

  Methods: Based on the genetic predisposition idea, we diagnosed and followed a total of ten individuals of relatives with mesothelioma. DNA was isolated from peripheral blood and whole genome sequencing analysis was done. Common gene mutations in ten individuals were filtered using bioinformatics. After this filter, from the remaining variants, very rare in the population and damaging mutations are selected.

  Results: Eight thousand six hundred and twenty-two common variants have been identified in ten individuals with this analysis. In total, 120 variants were found on 37 genes in 15 chromosomes. These genes are PIK3R4, SLC25A5, ITGB6, PLK2, RAD17, HLA-B, HLA-DRB1, HLA-DQB1, GRM, IL20RA, MAP3K7, RIPK2, and MUC16.

  Conclusion: Our finding, PIK3R4 gene, is directly associated with mesothelioma development. Twelve genes, which are associated with cancer, were detected in literature. Additional studies, which scan first-degree relatives of individual, are needed to find the specific gene region.

  © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

• Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion. X. Xie, M. You, E. Meng, et al. 2022;148(9):2561-2566. Case report · Letter PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is a rare and deadly malignancy with an extremely poor prognosis. The median overall survival (OS) of this disease is 12-18 months. However, the oncogenic driver mutations of MPM are rarely understood, and the targeted therapy for it is still under investigation. In this report, we describe a case of MPM with CD74-ROS1 fusion who obtains complete and durable response after receiving crizotinib. By the time of submission, the progression-free survival (PFS) with crizotinib has been 6.0 years, and the patient has survived for 7.6 years. Currently, he is still in complete remission (CR). To the best of our knowledge, this case represents the first report of CD74-ROS1 fusion identified in MPM. Meanwhile, it is also the first report of complete and long-term response to crizotinib in a patient with MPM positive for CD74-ROS1 fusion. This case report might contribute to the tumorigenesis and targeted therapy of this deadly disease.

  © 2022. The Author(s).

• Multi-institutional survey of malignant pleural mesothelioma patients in the Hokushin region. H. Uramoto, T. Takiguchi, T. Koizumi, et al. 2022;148(5):1153-1158. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a major occupational and environmental neoplasm. The purpose of this study was to validate the clinical and epidemiological factors, diagnosis, and initial treatment among MPM patients in the Hokushin region.

  Methods: We surveyed retrospective data from 152,921 cancer patients in 22 principal hospitals.

  Results: A total of 166 MPM cases were newly diagnosed. These patients consisted of 136 men and 30 women, with a median age of 69 years. We estimated the incidence rate for MPM to be 0.55 cases per 100,000 person-years in this study. The ratio per 100,000 population-years was 0.39 in Fukui, 0.60 in Ishikawa, 1.02 in Toyama and 0.35 in Nagano. Forty-five patients were discovered when diagnosed incidentally in patients under observations for other diseases. Forty-six cases were diagnosed as localized disease, while 13 had accompanying regional lymph node metastasis. Furthermore, 44 cases showed infiltration into adjacent organs. A histo-cytological diagnosis was made in 164 cases (98.8%). A surgical approach, chemotherapy, and radiotherapy were performed for 33, 88, and 6 patients, respectively, while 44 patients (26.5%) received best supportive care. Multimodality therapy was conducted in just 3.0% of the MPM patients CONCLUSION: MPM has a tragically rapid progression if discovered under observations for other diseases. Workers in health-related fields should be on high alert for aggressive MPM. Better evaluation and multi-disciplinary approaches to MPM in these regions are needed to optimize multimodality therapy.

  © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

• Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis. R. Carosio, V. Fontana, L. Mastracci, et al. 2021;147(2):459-468. PubMed · Publisher · Free full text

  Abstract

  Purpose: Programmed death-ligand 1 (PD-L1) protein plays a central role in the antitumor immune response, and appears to be a predictor of prognosis and efficacy for PD-L1 and programmed death 1 (PD-1) blockade therapy. The immunoregulatory role and prognostic impact of PD-L1 soluble form (sPD-L1) have been investigated in biological fluids of patients with different tumors. In malignant pleural mesothelioma (MPM), circulating sPD-L1 has been recently reported in patients' sera, but no data are available in pleural effusions (PE). In our study, we evaluated the baseline expression levels of sPD-L1 in PE from 84 MPM patients and correlated them with PD-L1-status in matched tumors and patients' overall survival (OS).

  Methods: sPD-L1 in PE was determined by ELISA and tumor PD-L1 by immunohistochemistry. Association of sPD-L1 with OS was estimated using the Cox regression model.

  Results: We observed that sPD-L1 was variably expressed in all the PE and tended to be higher (by 30%) in patients with PD-L1-positive tumors (cut-off ≥ 1% stained cells) as compared to patients with PD-L1-negative tumors (geometric mean ratio = 1.28, P value = 0.288). sPD-L1 levels were significantly higher than those of sPD-1 (P value = 0.001) regardless of the MPM histotypes and they were positively correlated (r = 0.50, P value < 0.001). Moreover, high PE sPD-L1 concentrations were associated with a trend towards increased OS (hazard ratio 0.79, 95% CL 0.62-1.01, P value = 0.062).

  Conclusions: Our study documents the presence of sPD-L1 in PE of MPM patients, and suggests its possible biological and prognostic role in MPM.

• Clinicopathological characteristics and outcomes in men with mesothelioma of the tunica vaginalis testis: analysis of published case-series data. J.B. Grogg, J.N. Fronzaroli, P. Oliveira, et al. 2021;147(9):2671-2679. PubMed · Publisher · Free full text

  Abstract

  Purpose: Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor, and currently, there are no published treatment recommendations.

  Methods: We performed a systematic literature review and synthesized clinical presentation, clinicopathological factors associated with metastatic disease, treatment options, and outcomes in men with MTVT.

  Results: We included 170 publications providing data on 275 patients. Metastatic disease occurred in 84/275 (31%) men with malignant MTVT: Most common sites included retroperitoneal lymph nodes (LNs) (40/84, 48%), lungs (30/84, 36%), and inguinal LNs (23/84, 27%). Invasion of the spermatic cord or scrotum was the only risk factor for local recurrence [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.36-7.57]. Metastatic disease was associated with age ≥ 42 years (OR 3.02, 95% CI 1.33-6.86), tumor size ≥ 49 mm (OR 6.17, 95% CI 1.84-20.74), presence of necrosis (OR 8.31, 95% CI 1.58-43.62), high mitotic index (OR 13.36, 95% CI 1.53-116.51) or angiolymphatic invasion (OR 3.75, 95% CI 1.02-13.80), and local recurrence (OR 4.35, 95% CI 2.00-9.44). Complete remission in the metastatic setting was observed in five patients, most of whom were treated with multimodal therapy. Median survival in patients with metastatic disease was 18 months (IQR 7-43).

  Conclusion: Malignant MTVT is a rare but aggressive disease. Since local recurrence is a risk factor for metastatic progression, we recommend aggressive local treatment. Survival and response to any treatment in the metastatic setting are limited.

  © 2021. The Author(s).

2010s

• The hippo pathway provides novel insights into lung cancer and mesothelioma treatment. X.L. Liu, R. Zuo, W.B. Ou. 2018;144(11):2097-2106. Review PubMed · Publisher · Free full text

  Abstract

  Purpose: Lung cancer and mesothelioma are two types of respiratory disease that have fatal courses and poor prognoses. Although a substantial number of targeted small molecules and antibody drugs have been developed, the 5-year survival rates of these patients remain relatively low. Moreover, most patients inevitably develop clinical resistance to treatment. Therefore, novel therapeutic options and cancer prognostic biomarkers are urgently needed.

  Methods: In this review, we summarized the recent literature from various electronic databases, including PubMed, and highlighted the most advanced findings regarding the hippo pathway in lung cancer and mesothelioma.

  Conclusion: The hippo signaling transduction pathway has been demonstrated to play crucial roles in lung cancer and mesothelioma pathogenesis, including tumor development and multidrug resistance, and is emerging as a promising therapeutic target, potentially providing new tools for the detection of these tumors at an early stage.

• Stomach cancer mortality among workers exposed to asbestos: a meta-analysis. W.J. Peng, X.J. Jia, B.G. Wei, et al. 2015;141(7):1141-9. Meta-analysis · Systematic review PubMed · Publisher · Free full text

  Abstract

  Background: The relationship between asbestos and stomach cancer is not well understood because of small number of cases. This study aimed to determine the incidence and mortality of stomach cancer among workers exposed to asbestos based on a systematic review and meta-analysis approach.

  Methods: Relevant English electronic databases were systematically searched for published studies characterizing the risk of developing stomach cancer as a result of asbestos exposure. Standardized mortality rate (SMR) for stomach cancer with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA.

  Results: A total of 32 independent studies were included for the analysis. The overall SMR for stomach cancer was 1.19 (95% CI 1.06-1.34), with a moderate degree of heterogeneity across the studies (I(2) = 37.6%, P = 0.011). Being male, exposure to crocidolite, miners, studies conducted in Europe and Oceania, and long study follow-up (≥ 25 years) all contribute to significantly higher SMR. Significant publication bias was observed.

  Conclusion: Elevated risk of stomach cancer mortality was evidenced among workers exposed to crocidolite, especially male miners.

• Oestrogen receptors are prognostic factors in malignant peritoneal mesothelioma. K. Pillai, M.H. Pourgholami, T.C. Chua, et al. 2013;139(6):987-94. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer. Females are found to survive longer than males after treatment, suggesting a possible involvement of hormonal factors. Estradiol is involved in cellular proliferation of a number of cancers and acts mainly through oestrogen receptors (ERs). Hence, we examined the expression of oestrogen receptors with correlation to prognosis.

  Methods: Oestrogen receptors expression was examined using immunohistochemistry on 42 paraffin-embedded sections of MPM tumours. Kaplan-Meier survival curves were analysed to determine the significance of ER expression in relation to prognosis.

  Results: ER-β (nuclear) was detected in 33 (79 %) patients. ER-β was also detected in the cellular cytoplasm of 9 (21 %) patients. Presence of ER-β (nuclear) was associated with favourable survival (univariate analysis, P = 0.001), whereas the presence of ER-β (cytoplasm) was associated with a poor survival (P = 0.014). Multivariate Cox regression analysis revealed the absence of ER-β (nuclear) and the presence of ER-β (cytoplasm) to be independent predictive factors for poor disease outcome (hazard ratio 5.4, 95 % confidence interval 1.86-15.75; P = 0.002 and hazard ratio 8.0, 95 % confidence interval 1.8-34; P = 0.005), respectively. ER-α (nuclear) was detected in only 4 (9 %) of patients and not statistically significant (univariate analysis, P = 0.066).

  Conclusion: The presence of ER-β (cytoplasm) is associated with poor prognosis. The favourable survival association observed in patients with ER-β (nuclear) raises a question about the molecular mechanisms of the tumorigenic roles of ER-β in each cellular compartment and requires further studies.

• Prognostic nutritional index predicts outcomes of malignant pleural mesothelioma. Z.H. Yao, G.Y. Tian, Y.Y. Wan, et al. 2013;139(12):2117-23. PubMed · Publisher · Free full text

  Abstract

  Purpose: Nutritional status has been associated with long-time outcomes in cancer patients. We investigated whether the prognostic nutritional index (PNI), an indicator of nutritional status, affects overall survival in patients with malignant pleural mesothelioma (MPM).

  Methods: We enrolled 121 patients with histologically confirmed MPM, who had successfully undergone biopsy by medical thoracoscopy in this study. Demographic, clinical and laboratory data were collected retrospectively. The PNI was calculated as 10× serum albumin value (g/dl) + 0.005 × total lymphocyte count (per mm(3)) in peripheral blood. Univariate and multivariate analyses were used to identify prognostic factors.

  Results: Mean pretreatment PNI was 44.6. PNI was significantly associated with age (P = 0.031), smoking habits (P = 0.039) and weight loss (P = 0.029). Survival analysis showed PNI to be an independent prognostic factor in MPM. Patients with lower PNIs (PNI < 44.6) had greater risk of death than those with higher PNIs (PNI ≥ 44.6; hazard ratio: 2.290; 95 % confidence interval: 1.415-3.706; P = 0.001). These analyses were adjusted for patient age, gender, smoking habits, dyspnea, chest pain, weight loss, primary site of tumor, histology, platinum-based systemic chemotherapy, hospital and stage.

  Conclusions: Pretreatment PNI is a novel independent prognostic factor in MPM.

• DNA methylation status of REIC/Dkk-3 gene in human malignancies. T. Hayashi, H. Asano, S. Toyooka, et al. 2012;138(5):799-809. PubMed · Publisher · Free full text

  Abstract

  Purpose: The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies.

  Methods: We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed.

  Results: The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group.

  Conclusions: REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies.

• BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients. J. Hmeljak, N. Erčulj, V. Dolžan, et al. 2011;137(11):1641-51. PubMed · Publisher · Free full text

  Abstract

  Purpose: Malignant pleural mesothelioma is an incurable, asbestos-associated cancer. Its incidence is rapidly increasing and survival remains short. Apoptosis deregulation is an important feature of cancer and survivin, a member of the inhibitor-of-apoptosis-protein family encoded by the BIRC5 gene, has been suggested to have a role in the development and progression of several cancers. Genetic variability, in particular single nucleotide polymorphisms in the BIRC5 promoter, may affect the protein's expression levels. The aim of our study was to elucidate the effects of BIRC5 promoter single nucleotide polymorphisms on survivin expression, patient survival and age at diagnosis in malignant pleural mesothelioma.

  Methods: Archival mesothelioma samples from 101 Slovenian patients were immunohistochemically analysed for survivin expression. DNA was extracted from tumour samples and genotyped for three BIRC5 promoter single nucleotide polymorphisms (-31G > C, -241C > T and -625G > C). Genotypes were associated with nuclear survivin expression. Nuclear survivin expression, genotypes, haplotypes, histological type, gender and asbestos exposure were included in univariate Cox survival analyses.

  Results: Survivin expression was detected in both tumour cell nuclei and cytoplasms in all analysed samples. No association between BIRC5 promoter polymorphism genotypes or haplotypes and nuclear survivin expression was found. Polymorphism -241C > T affected patients' age at diagnosis. Survival analysis confirmed that younger age at diagnosis and epitheloid histological type improved survival, but no significant effects of nuclear survivin expression or genotype/haplotype on overall survival were observed.

  Conclusion: Our findings indicate no relationship between BIRC5 genotypes and survivin expression or overall survival in mesothelioma patients. We observed that BIRC5 -241C > T polymorphism had a significant effect on patient age at diagnosis.

• Clinical investigation of malignant mesothelioma in Japan. N. Fujimoto, K. Aoe, K. Gemba, et al. 2010;136(11):1755-9. PubMed · Publisher · Free full text

  Abstract

  Purpose: The asbestos-related problems caused much social concern; however, no large-scale study was conducted about clinical features of MM in Japan. Patients with MM who have a history of occupational asbestos exposure (AE) are provided worker's compensation in Japan. However, only about 10% of MM cases were actually claimed and compensated. So there is still controversy over the association between MM and AE. The aim of this study is to investigate the clinical features of MM. We also aimed to clarify the association between MM and occupational AE in Japan.

  Methods: We examined the clinical features of MM cases. Clinical information was obtained including gender, age, site of origin, pathological subtype, radiological findings, and treatment outcome. To investigate the association between MM and AE, investigators interviewed all patients regarding work and residential history.

  Results: Between January 2005 and December 2007, 105 cases (median age: 63 years, range 35-80, male/female: 88/17) were diagnosed with MM in the Rosai Hospital group and related facilities. Among them, 94(89.5%) cases originated in the pleura, 7(6.7%) in the peritoneum, 2(1.9%) in the pericardium, and 1(0.9%) in the tunica vaginalis testis. There were 69(65.7%) epithelioid, 19(18.1%) biphasic, 16(15.2%) sarcomatoid, and 1 unclassified pathological subtypes of MM. A favorable survival rate was indicated in the patient group of MPM that underwent surgery compared to others, though it was not statistically significant (P = 0.1743). The occupational AE was indicated in 89 cases (84.8%). Three patients had no history of occupational AE, but lived with someone who was in an occupation that handled asbestos. There were two patients in which AE was indicated in their life environment. Altogether, AE was indicated in 93(88.6%) patients.

  Conclusions: This study stresses the urgent need for physicians to acknowledge the association between MM and AE, and to inquire thoroughly regarding AE to the patients with MM.

2000s

• Hyperthermia and mafosfamide in a human-derived malignant pleural mesothelioma cell line. E.M. Ehlers, W. Kühnel, G.J. Wiedemann. 2002;128(2):65-72. PubMed · Publisher · Free full text

  Abstract

  Purpose: Diffuse malignant pleural mesothelioma is the most common primary pleural malignancy. At the beginning of the last century, this tumor was of minor incidence. Meanwhile, the use of asbestos has led to and is still leading to a rise in pleural mesothelioma incidence. There is no standard therapy for this highly aggressive disease and the development of new therapeutic strategies is imperative.

  Methods: We, therefore, investigated the morphological and pharmakokinetic effects of a combined thermochemotherapy consisting of the administration of different dosages of mafosfamide with and without the application of a 1-h hyperthermia at 41.7 degrees C on the human biphasic malignant pleural mesothelioma cell line MSTO-211H. After therapy, cells were prepared for light and electron microscopy. BrdU-incorporation for the S-phase fraction, TUNEL-labeling for detection of apoptosis, and quantitative assessments using the MTT assay were performed.

  Results: Our results demonstrate that the combination of mafosfamide with hyperthermia leads to qualitatively and quantitatively enhanced cellular damage compared to monotherapy. During combined thermochemotherapy, cell damage and death is already induced at lower mafosfamide concentrations than without hyperthermia which suggests an additive effect from hyperthermia to the action of the alkylating drug mafosfamide. Cell death thereby mostly occurs as necrotic cell death rather than as apoptosis, although in a combined thermochemotherapy apoptosis is induced temperature-dependently, when comparing temperatures from 37 degrees C to 43 degrees C.

  Conclusions: We suggest that the effect of substances such as ifosfamide and cyclophosfamide which are in clinical use, might be enhanced by the combination of local or regional hyperthermia in order to improve the therapeutical index of these substances in the treatment of pleural mesothelioma.

• Pleural mesothelioma associated with indoor pollution of asbestos. J. Schneider, K. Rödelsperger, B. Brückel, et al. 2001;127(2):123-7. Case report PubMed · Publisher · Free full text

  Abstract

  This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.

1990s

• Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. E. Tolnay, C. Kuhnen, T. Wiethege, et al. 1998;124(6):291-6. PubMed · Publisher · Free full text

  Abstract

  Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, motility and invasiveness via its receptor c-Met during embryogenesis and repair processes. It induces angiogenesis, promoting endothelial cell migration and capillary-tube formation in vivo. Co-expression of HGF/SF and c-Met receptor results in enhanced tumour growth, invasiveness and a mesenchymal-epithelial transition in some experimental tumours. Since mesothelioma cells have been reported to express c-Met receptor and to migrate in response to HGF/SF, we investigated human malignant pleural mesotheliomas for the demonstration of possible co-expression of the growth factor and its receptor. The microvessel density of the tumours was also analysed in order to assess the influence of HGF/SF expression on tumour angiogenesis. Thirty-nine paraffin-embedded specimens of malignant pleural mesotheliomas were immunostained by anti-HGF/SF and anti-c-Met antibodies and semiquantitatively evaluated. c-Met mRNA expression was visualised in ten tumour samples by a fluorescent in situ hybridisation method. Microvessel density was calculated by counting microvessels with a high-power field (200x) on von-Willebrand-factor-stained slides. We found an increased production of HGF/SF in 33/39 tumours and a corresponding overexpression of c-Met receptor in 29/39 specimens. The FISH method detected increased transcription of c-Met mRNA in malignant cells and in neighbouring vascular endothelial cells. HGF/SF-positive mesotheliomas had significantly higher microvessel densities compared to their HGF/SF-negative counterparts. The observed co-expression of HGF/SF and c-Met in malignant pleural mesotheliomas suggests a possible self-stimulation (autocrine loop) of tumour cells. On the basis of the significantly higher microvessel density values of malignant mesotheliomas overexpressing HGF/SF, we postulate, that HGF/SF may be an additional relevant factor in tumour angiogenesis in malignant pleural mesotheliomas.

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