Tumour Biology

Our medical research library holds 12 studies published in Tumour Biology (1998–2017). 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. 12 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: SAGE Publications
• Published: 1984 to the present, United States
• Language: English
• ISSN: 1010-4283 (print), 1423-0380 (electronic)
• Continues: Oncodevelopmental Biology and Medicine
• Its record in the NLM Catalog

2010s

• Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer. X.Y. Wang, Z. Wang, J.B. Huang, et al. 2017;39(6):1010428317699111. PubMed · Publisher

  Abstract

  BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.

• Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma. H. Liu, L. Wu, K. Ji, et al. 2015;36(10):7375-84. Review PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient's tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease.

• Secreted frizzled-related protein 4 and its implications in cancer and apoptosis. S. Pohl, R. Scott, F. Arfuso, et al. 2015;36(1):143-52. Review PubMed · Publisher

  Abstract

  Secreted frizzled-related protein 4 (SFRP4) is a glycoprotein that acts as an antagonist of Wnt ligands, causing inhibition of the canonical Wnt signalling pathway. First noticed due to high expression levels during times of increased apoptosis, SFRP4 has been implicated in cell proliferation and differentiation and plays an important role in carcinogenesis. Many tumours such as endometrial, cervical, ovarian, prostate, bladder, colorectal, mesothelioma, pancreatic, renal, and oesophageal tumours are characterised by aberrant promoter hypermethylation, which causes variations in the expression level of SFRP4 when compared to normal cells. Combined experimental data appear to confirm the suggested role of SFRP4 as a local initiator of apoptosis; however, increased SFRP4 expression may not always correlate with an increase in apoptosis, possibly due to the complex interactions between different signalling pathways. SFRP4 can be explored for its use in novel therapeutic modalities as well as being a potential diagnostic biomarker.

• Bladder cancer invasion predictability based on preoperative neutrophil-lymphocyte ratio. M. Kaynar, M.E. Yıldırım, H. Badem, et al. 2014;35(7):6601-5. PubMed · Publisher

  Abstract

  An increased pretreatment neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis in colorectal, gastric, and ovarian cancer; malignant mesothelioma; and renal cell carcinoma. The present study aims to define the predictive value of preoperative peripheral blood count NLR in non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease (MIBC) patients. There were in total 291 patients, 241 males and 50 females. Out of these, 156 male and 36 female patients were in the NMIBC group and 85 male and 14 female patients in the MIBC group. In the NMIBC group, 172 patients had low-grade and 20 high-grade papillary urothelial carcinoma. The mean age of the patients in the NMIBC group was 64 ± 13, ranging from 27 to 97. The mean age of the patients in MIBC group was 70.5 ± 10, ranging from 27 to 95. A statistically significant relation between patient ages and tumor invasiveness was determined (p = 0.023, 95 % confidence interval (CI) 63.3-66.7). The mean tumor size of the NMIBC group was 2.1 ± 1.09 (cm) (range 0.5-8), and of MIBC group 3.6 ± 1.5 (cm) (range 0.8-9). There was a statistically significant relation between the tumor size and invasiveness (p = 0.002, 95 % CI 2.8-4.4). In the NIMBC group, 149 (77.6 %) of them have NLR ≤ 2.5 and 43 (22.4 %) have NLR > 2.5. Also, in MIBC, 67 (67.7 %) of them have NLR ≤ 2.5 and 32 (32.3 %) have NLR > 2.5. The mean NLR in the NMIBC group was 2.4 ± 0.1 (range 0.08-6.49, 95 % CI 1.52-2.71) and in the MIBC 2.9 ± 0.2 (range 0.08-16.72, 95 % CI 1.67-2.97). In terms of NLR, there was a statistically significant difference between the NMIBC and MIBC groups (p = 0.028). Platelet-lymphocyte ratio (PLR) of the two groups was also analyzed. The PLR of the NMIBC group was 12.8 ± 15.1 (range 3.38-19.1) and of the MIBC 13.6 ± 8.78 (range 0.18-63), yet there was not any statistically significant difference (p = 0.810, 95 % CI 11.4-14.8) (Table 1). The correlation tests revealed a positive correlation between the age (r = 0.144, p = 0.024), tumor size (r = 0.193, p = 0.02), and tumor invasiveness NLR (r = 0.138, p = 0.031). NLR can be used to determine tumor invasiveness as a cost-effective, common, and simple biomarker in bladder cancer (BC).

• Serum albumin as a significant prognostic factor in patients with malignant pleural mesothelioma. Z.H. Yao, G.Y. Tian, S.X. Yang, et al. 2014;35(7):6839-45. PubMed · Publisher

  Abstract

  Our aim was to evaluate the prognostic role of the pretreatment serum albumin level in patients with malignant pleural mesothelioma (MPM) receiving platinum-based systemic chemotherapy. From 1995 to 2013, a total of 97 patients receiving platinum-based systemic chemotherapy for newly diagnosed MPM were enrolled. All clinical information and laboratory results were retrospectively collected from the medical records. The Kaplan-Meier method was used to calculate survival. The Cox proportional hazards model was used to identify significant independent prognostic factors for predicting survival. In total, 34 of the 97 patients (35.1 %) had hypoalbuminaemia (albumin ≤ 35 g/l). The 1-year overall survival rate was 44.1 % for patients with hypoalbuminaemia and 72.0 % for patients with a normal albumin level. Multivariate analysis indicated that pretreatment albumin was an independent prognostic factor in MPM. Patients with hypoalbuminaemia had a greater risk of death than those with a normal albumin level [hazard ratio (HR) 1.778; 95 % confidence interval (CI) 1.504-2.998; P = 0.031]. When albumin was entered as a continuous variable in the Cox regression model, the HR of death was significantly decreased by 9.8 % (95 % CI 0.851-0.956) for each 1-g/l increment. The pretreatment serum albumin level is a simple, inexpensive and easily measurable marker with prognostic significance in MPM patients treated with platinum-based systemic chemotherapy.

• The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms. L.V. de Assis, M.C. Isoldi. 2014;35(2):889-901. Review PubMed · Publisher

  Abstract

  The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.

• PTEN protein expression in malignant pleural mesothelioma. V. Agarwal, A. Campbell, K.L. Beaumont, et al. 2013;34(2):847-51. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma is associated with poor prognosis and despite recent advances in chemotherapy, the median survival is still approximately 12 months. Loss of phosphatase and tensin homolog (PTEN) protein expression may lead to constitutive activation of AKT resulting in cell survival and proliferation. Small studies reported that PTEN protein expression is rarely lost in mesothelioma whilst a larger study demonstrated prognostic significance of PTEN protein expression status with absence in 62 % of cases. We aimed to analyse PTEN protein expression in mesothelioma. Immunohistochemical analysis was performed in 86 archival mesothelioma samples to determine the PTEN protein expression status and statistical analysis was performed to identify any prognostic significance. Mesothelial cells in normal pleura demonstrated positive staining for PTEN protein and served as a positive reference. For mesothelioma samples, the expression of PTEN protein was scored as 0 (negative), 1 (intensity less than that of positive normal pleura reference slide) and 2 (intensity equal to or greater than positive normal pleura reference slide). A total of 23/86 (26.7 %) scored 0, 23/86 (26.7 %) scored 1 and 40/86 (46.5 %) scored 2 for PTEN expression. Univariate analysis demonstrated that lack of PTEN expression was not associated with survival. PTEN protein expression was undetectable in 26.7 % of mesothelioma samples; however, no prognostic significance was identified. Absence of PTEN protein may result in activation of the PI3K/AKT/MTOR pathway. Targeting this pathway with inhibitors further downstream of PTEN may provide a potential therapeutic target in selected patients.

• Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma. R. Hama, Y. Watanabe, K. Shinada, et al. 2012;33(6):2031-40. PubMed · Publisher

  Abstract

  Malignant mesothelioma (MM) is a rare disease with a poor prognosis. Pleural mesothelioma, which is the most common type of MM, is considered to be caused by asbestos exposure and is increasing in incidence, with about 15,000 new cases diagnosed worldwide annually. On the other hand, peritoneal mesothelioma is a very rare type of MM; thus, its pathogenesis is even less understood than pleural mesothelioma. Recent research on the pathogenesis of malignant pleural mesothelioma has indicated that both epigenetic and genetic alterations contribute to tumorigenesis. Here, we hypothesize that peritoneal mesothelioma also has an epigenetic alteration in the same genes (Kazal-type serine peptidase inhibitor domain 1 (KAZALD1), transmembrane protein 30B (TMEM30B), and mitogen-activated protein kinase 13 (MAPK13)). Our goal is to identify DNA methylation of these three candidate genes in two peritoneal mesothelioma cases. Laser capture microdissection was used to separate diseased sections of formalin-fixed paraffin-embedded samples from one surgically resected tissue (epithelial type) and one autopsy tissue (sarcomatous type). Genomic DNA was subsequently extracted by the standard phenol chloroform method. The DNA was then treated with sodium bisulphite, and pyrosequencing analysis was used to quantitatively analyze the methylation of candidate genes reported to be hypermethylated in malignant pleural mesothelioma (KAZALD1, TMEM30B, and MAPK13). TMEM30B and MAPK13 were not methylated in either case. However, KAZALD1 was highly methylated in sarcomatoid-type peritoneal mesothelioma. We first report that the KAZALD1 gene was hypermethylated in sarcomatoid-type malignant peritoneal mesothelioma.

• Effects of hyaluronic acid and CD44 interaction on the proliferation and invasiveness of malignant pleural mesothelioma. T. Hanagiri, S. Shinohara, M. Takenaka, et al. 2012;33(6):2135-41. PubMed · Publisher

  Abstract

  Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25 μg/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA-CD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA-CD44 interaction is a potentially useful therapeutic target in MPM.

• Environmental factors in causing human cancers: emphasis on tumorigenesis. U.T. Sankpal, H. Pius, M. Khan, et al. 2012;33(5):1265-74. Review PubMed · Publisher

  Abstract

  The environment and dietary factors play an essential role in the etiology of cancer. Environmental component is implicated in ~80 % of all cancers; however, the causes for certain cancers are still unknown. The potential players associated with various cancers include chemicals, heavy metals, diet, radiation, and smoking. Lifestyle habits such as smoking and alcohol consumption, exposure to certain chemicals (e.g., polycyclic aromatic hydrocarbons, organochlorines), metals and pesticides also pose risk in causing human cancers. Several studies indicated a strong association of lung cancer with the exposure to tobacco products and asbestos. The contribution of excessive sunlight, radiation, occupational exposure (e.g., painting, coal, and certain metals) is also well established in cancer. Smoking, excessive alcohol intake, consumption of an unhealthy diet, and lack of physical activity can act as risk factors for cancer and also impact the prognosis. Even though the environmental disposition is linked to cancer, the level and duration of carcinogen-exposure and associated cellular and biochemical aspects determine the actual risk. Modulations in metabolism and DNA adduct formation are considered central mechanisms in environmental carcinogenesis. This review describes the major environmental contributors in causing cancer with an emphasis on molecular aspects associated with environmental disposition in carcinogenesis.

2000s

• Serum PDGF-AB in pleural mesothelioma. R. Filiberti, P. Marroni, M. Neri, et al. 2005;26(5):221-6. PubMed · Publisher

  Abstract

  Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean+2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR=1.2, 95%CI: 0.9-1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.

  Copyright (c) 2005 S. Karger AG, Basel.

1990s

• Identification of a differential expression of two cDNAs between malignant mesothelioma and normal mesothelial cells using the RNA fingerprint method. S. Frank, B.U. von Specht, W. Sendt, et al. 1998;19(3):153-9. PubMed · Publisher

  Abstract

  The RNA fingerprint method was used to identify mRNAs that were differentially expressed during the development of human mesothelial cell cancer. We report the isolation of two differentially expressed clones. One clone was expressed in the metastatic mesothelioma cell line M1A and in the malignant mesothelioma cell line M1 and downregulated in normal mesothelial cells. M1 and M1A were derived from a primary and metastatic tumor of the same patient. The other clone was only expressed in normal mesothelial cells. The different expression pattern was confirmed by Northern blot analysis. One clone had a striking sequence homology to the soares pregnant uterus NbHPU homo sapiens cDNA clone. The other clone contained a high sequence homology to the human mRNA for ORF. The biological function of the corresponding genes is unknown. The specificity of expression of the two sequence tags was further examined on different cancer cell lines and normal tissues.

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