BMC Research Notes

Our medical research library holds 14 studies published in BMC Research Notes (2012–2023). 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. 14 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Biomed Central
• Published: 2008 to the present, England
• Language: English
• ISSN: 1756-0500 (electronic)
• Its record in the NLM Catalog

2020s

• ATG5 as biomarker for early detection of malignant mesothelioma. M. Tomasetti, F. Monaco, O. Strogovets, et al. 2023;16(1):61. PubMed · Publisher · Free full text

  Abstract

  Objectives: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.

  Results: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.

  © 2023. The Author(s).

• Development of a quantitative methylation-specific droplet digital PCR assay for detecting Dickkopf-related protein 3. K. Araki, A. Kurosawa, H. Kumon. 2022;15(1):169. PubMed · Publisher · Free full text

  Abstract

  Objective: The detection and monitoring of DNA methylation status in circulating tumor cell DNA (ctDNA) provides critical insights into cancer diagnosis and progression. The methylation status of the Dickkopf-related protein 3 (DKK3) promoter region is correlated with the metastasis and recurrence of multiple cancers. Thus, detecting the methylation status via non-invasive methods is essential for the diagnosis and prognosis of cancers. Using a droplet digital polymerase chain reaction approach, we have developed a highly sensitive and quantitative measurement of methylated and unmethylated DKK3 derived from circulating cell-free DNA (ccfDNA).

  Results: We confirmed the specificity of droplet digital methylation specific polymerase chain reaction (ddMSP). We selected the optimal bisulfite conversion method using commercially available kits. We validated the ddMSP analysis system by analyzing the methylation status of genomic DNA extracted from cultured mesothelioma cells and mesothelial cells. Our system quantified approximately 30 copies of cell-free DNA per 4 mL, which is sufficient for detecting ctDNA. Finally, we quantified methylated and unmethylated DKK3 copies in ccfDNA from 21 patients with malignant mesothelioma.

  © 2022. The Author(s).

• Determinants of plasma calretinin in patients with malignant pleural mesothelioma. M. Lehnert, D.G. Weber, D. Taeger, et al. 2020;13(1):359. PubMed · Publisher · Free full text

  Abstract

  Objective: Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA).

  Results: The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.

• Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model. S.A. Fisher, C.J. Peddle-McIntyre, K. Burton, et al. 2020;13(1):435. PubMed · Publisher · Free full text

  Abstract

  Objective: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.

  Results: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non-asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre-clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.

2010s

• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study. D.G. Weber, A. Brik, S. Casjens, et al. 2019;12(1):77. PubMed · Publisher · Free full text

  Abstract

  Objective: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.

  Results: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.

• Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy. L. Vimercati, D. Cavone, A. Caputi, et al. 2019;12(1):636. PubMed · Publisher · Free full text

  Abstract

  Objective: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma.

  Results: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.

• Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013. B.D. Kerger. 2018;11(1):337. PubMed · Publisher · Free full text

  Abstract

  Objective: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years).

  Results: Gender-specific time trends in age-adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74 years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity-related factors.

• Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors. J. Chee, M.W. Watson, A. Chopra, et al. 2018;11(1):864. PubMed · Publisher · Free full text

  Abstract

  Objective: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.

  Results: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.

• The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection. P. Winata, M. Williams, E. McGowan, et al. 2017;10(1):600. PubMed · Publisher · Free full text

  Abstract

  Objective: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR.

  Results: The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.

• Co-existing tuberculosis and malignant mesothelioma with multiple sites venous thrombosis: a case report. P. Kumar, K. Chawla, P. Khosla, et al. 2016;9(1):409. Case report PubMed · Publisher · Free full text

  Abstract

  Background: Tuberculosis is endemic in India and almost 40 % of the Indian population is infected with tubercle bacilli. Tuberculosis being a great mimicker of infectious as well as non infectious diseases and recent rise of multi drug resistant and extended drug resistant cases have made diagnosis and management more difficult. To the best of our knowledge there have been no reported cases of tuberculosis coexisting with malignant peritoneal mesothelioma leading to multiple site venous thrombosis.

  Case Presentation: Forty five year old male, belonging to Indian/Aryan ethnicity presented with cough, breathlessness and fever for 7 months with past history of pulmonary tuberculosis. On examination he was found to have pleural effusion for which he received anti-tuberculosis therapy empirically. Later his condition deteriorated and on further examination he was found to have ascites, multiple site venous thrombosis and pyothorax which was found positive for acid fast bacilli. Despite anti-tuberculosis therapy he did not improve and was suspected to be a multidrug resistant case. Later on computed tomography peritoneal nodule was detected and on biopsy revealed malignant mesothelioma.

  Conclusion: In a diagnosed case of tuberculosis with clinical findings compatible with it but not responding to anti tubercular therapy, underlying secondary co-existing pathology should be explored.

• Establishment of anti-mesothelioma monoclonal antibodies. N. Mizutani, M. Abe, S. Matsuoka, et al. 2016;9:324. PubMed · Publisher · Free full text

  Abstract

  Background: Mesotheliomas are aggressive, therapy-resistant tumors that are predicted to increase in incidence at least until 2020. The prognosis of patients with mesothelioma is generally poor because they are typically diagnosed at a late stage and their tumors are resistant to current conventional therapies. For these reasons, improved diagnosis and therapy are urgently required. To address these issues, the aim of our research was to develop novel mesothelioma-specific monoclonal antibodies (mAbs) as diagnostic and therapeutic agents.

  Methods: To develop anti-mesothelioma mAbs useful for diagnosis and therapy, we repeatedly immunized a BALB/c mouse with viable mesothelioma cells, alternating between those from three mesothelioma cell lines. We hybridized the spleen cells from this immunized mouse with P3U1 myeloma cells. We then screened supernatants harvested from the hybridoma clones by assessing whether they bound to a mesothelioma cell line not used for immunization and altered its morphology. We designed this developmental strategy to reduce the risk of obtaining clonotypic mAbs against a single mesothelioma cell line.

  Results: Our newly generated mouse anti-human mAbs immunostained clinical samples of mesotheliomas. One of the newly generated mAbs did not react with any other tumor cell line tested. Two other mAbs significantly inhibited the proliferation of mesothelioma cells.

  Conclusion: These newly generated anti-mesothelioma mAbs are potentially useful as diagnostic and therapeutic agents for mesothelioma. Moreover, our novel strategy for establishing antitumor mAbs may facilitate the development of new diagnostic and therapeutic techniques for mesotheliomas and other malignancies.

• Concurrent occurrence of renal cell carcinoma with rhabdoid features in a married couple: a case report. R. Matsumoto, N. Shinohara, K. C-Hatanaka, et al. 2015;8:3. Case report PubMed · Publisher · Free full text

  Abstract

  Background: Renal cell carcinoma (RCC) with rhabdoid features is a rare histology and exhibits clinically aggressive behavior. We report a case of a married couple in whom RCC with rhabdoid features concurrently occurred. The rarity of this event suggests that environmental factors may contribute to the etiology of RCC with rhabdoid features.

  Case Presentation: A 76-year-old Japanese woman was diagnosed with a hypervascular mass in the right kidney and tumor thrombus extending into the right atrium by enhanced computed tomography (CT). She underwent radical nephrectomy and tumor thrombectomy following systemic therapy with the tyrosine kinase inhibitor sunitinib. The histological evaluation denoted clear cell RCC with rhabdoid features. The patient died of cancer 12 months postoperatively. A 76-year-old man, her husband, presented with gross hematuria 2 weeks after his wife had undergone surgery. He had a long history of asbestos exposure. An abdominal CT scan revealed a hypervascular mass in the right kidney and tumor thrombus extending into the inferior vena cava. He also underwent radical nephrectomy and tumor thrombectomy. The histological evaluation also showed clear cell RCC with rhabdoid features. Bone metastasis occurred 12 months postoperatively, but he died of an unrelated cause 18 months after surgery.

  Conclusion: Concurrent occurrence of RCC with rhabdoid features may not to be coincidental. Although further studies are warranted, asbestos exposure may contribute to the etiology of clear cell RCC with rhabdoid features.

• Absence of amplification of the FGFR1-gene in human malignant mesothelioma of the pleura: a pilot study. T. Plönes, F. Beckers, W. Engel-Riedel, et al. 2014;7:549. PubMed · Publisher · Free full text

  Abstract

  Background: Mesothelioma (MPM) is a rare malignant disease with a worse outcome. Fibroblast growth factor 1 (FGFR1) may be an interesting target for selective tyrosine kinases inhibitors (TKI) in MPM. The aim of this study was to evaluate the amplification of the FGFR1 gene in patients suffering from MPM.

  Findings: We identified nineteen male patients treated in our department between August 2008 and July 2010 matching the inclusion criteria. Mean age was 68 years. Histopathological examination confirmed thirteen patients with epitheloid subtype, five with biphasic and one patient with sarcomatoid. Fluorescence in situ hybridization analysis revealed no polysomy nor an amplification of the FGFR gene copy number in any case.

  Conclusion: Regarding that also EGFR amplifications in MPM are absolute rarities, our findings may be a hint that TKI's will not satisfy the hope for a new era in the treatment of MPM.

• Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience. A. Bearz, R. Talamini, G. Rossoni, et al. 2012;5:482. PubMed · Publisher · Free full text

  Abstract

  Background: Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment.

  Methods: We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment.

  Results: Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively.

  Conclusions: In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression.

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