Mesothelioma Research Articles

Prognostic Factors of Long-Term Survival and Conditional Survival Analysis in MPM Patients Treated with CRS+HIPEC: A Retrospective Study of Two Centers.

This study was designed to explore the survival benefit factors of malignant peritoneal mesothelioma (MPM) patients after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to make dynamic survival prediction by conditional survival (CS). Data of 212 patients with MPM who underwent CRS+HIPEC were retrospectively analyzed. Patients were divided into long-term survival (LTS) group (≥48.0 months) and short-term survival (STS) group (≤16.0 months) according to OS. Conditional survival is the probability of surviving y years after already survived for x years. Univariate and multivariate analyses were performed to explore the favorable factors of LTS. Conditional survival and Kaplan-Meier were applied to assess the postoperative survival probability. Ninety patients were enrolled: 53 (58.9%) were LTS, and 37 (41.1%) were STS. Univariate analysis revealed 14 meaningful factors (P < 0.05): age, surgery history, Karnofsky performance status, pathological types, tumor vascular emboli, lymphatic metastasis, Ki-67 index, preoperative CA125 level, peritoneal cancer index (PCI), completeness of cytoreduction, bleeding, red blood cell (RBC) transfusion, ascites, and severe adverse events (SAEs). Multivariate analysis identified that PCI ≤ 20, less RBC transfusion and no SAEs were independent prognostic factors for LTS. Five-year CS increased from 27% at 0 years to 84% at 4 years with the increasing number of survival years. The survival curve flattens at postoperative 5 years. The key factors in CRS+HIPEC for MPM patients to achieve LTS are lower tumor burden, less intraoperative RBC transfusion, and prevention of SAEs. Malignant peritoneal mesothelioma patients demonstrated a substantial increase in CS over time. Some patients may achieve clinical cure 5 years after surgery.

A case of ovarian mesothelioma with VHL mutation diagnosed by immunohistochemistry and literature review

The malignant mesothelioma mainly develops in the pleura and peritoneum, while primary ovarian mesothelioma is very rare. Here, we report the first case of primary ovarian mesothelioma (clear cell variant) with VHL mutations in the world based on the results of histomorphology, immunohistochemistry, and genetic testing. This is an extremely rare type of tumor that has not been reported so far. Through the literature search, we reviewed primary ovarian mesothelioma, focusing on its differential diagnosis and molecular genetics. The purpose of this paper is to deepen the flexible selection and application of immunohistochemical markers in mesothelioma, so as to reduce missed diagnosis and misdiagnosis.

Abstract 4135447: Demographics, Clinicopathological Outcomes and Comparative Survival Analysis of Pleural and Pericardial Mesothelioma; A Retrospective Population-Based Study

Background: Malignant mesothelioma (MM) is an aggressive and rare tumor of mesothelial cells that is strongly correlated with asbestos exposure. Due to its long latency period, MM is characterized by its poor prognosis. In this study, we primarily analyzed data for the clinicopathological analysis of malignant pleural mesothelioma with comparative overall survival (OS) and cancer-specific survival (CSS) with primary pericardial mesothelioma. Method: The data was collected from the Epidemiology and End Results (SEER) database, comprising 12,991 mesothelioma patients from 2000 to 2020. Results: A total of 12,991 cases of MM were extracted from the database, of which 99.55% were pleural and only 0.177% were pericardial. The median age was 74 years. Regarding gender, 80% of the patients were male. MM was found to be more common in older age (&gt;65, 77%). 52% of the patients had a tumor size greater than 5 cm. The common histologic type was mesothelioma NOS (45%), followed by the epithelioid type (36%). The most common treatment modality was chemotherapy. Multivariate analysis showed better survival outcomes in younger, female patients undergoing combination therapies. Moreover, the histologic subtype, especially epithelioid mesothelioma, showed the overall best prognosis. Regarding comparative OS and CSS between pleural and pericardial mesothelioma, the 3-year OS of pleural mesothelioma was 11.2% (95% CI: 0.107 - 0.118) and for pericardial mesothelioma, the 3-year OS was 4.7% (95% CI: 0.007 - 0.317). Pleural mesothelioma had a 1-year CSS of 37.1% (95% CI: 0.343 - 0.401), and for pericardial mesothelioma, the CSS at 9 months was 28.6% (95% CI: 0.089 - 0.922), and all patients survived &lt; 1 year in the cohort. Conclusion: Malignant mesothelioma is a rare and aggressive tumor. Pericardial mesothelioma has lower survival in comparison to pleural mesothelioma. Genomic analysis and including all ethnicities in future clinical trials will help in future personalized therapeutic approaches.

Abstract 4136566: Primary Pericardial Mesothelioma: Diagnostic dilemma and rapid decline

Description of case: A 33-year-old man with no medical history or environment exposures, presented with dyspnea, nausea, and vomiting. He was tachycardic, with jugular venous distension, pulsus paradoxus, low voltage QRS and echocardiogram (TTE) showed a large pericardial effusion with ventricular interdependence. He underwent pericardiocentesis with negative fluid studies, including cytology. Two months later he represented with dyspnea and pleuritic chest pain, was diagnosed with pericarditis, and found to have recurrent pericardial effusion without tamponade. He was treated with aspirin and colchicine and discharged, with surveillance TTE showing a stable pericardial effusion but with significant adhesions and constrictive physiology (confirmed on right heart catheterization). Negative QuantiFERON was obtained and Anakinra started. Two months later he remained symptomatic with new pleural effusions and was sent for positron emission tomography scan which revealed diffuse intensely hypermetabolic pericardial thickening/fluid, up to 3.8 cm in maximal thickness and increased uptake in mediastinal nodes. Next, a cardiac MRI showed extensive circumferential thickening of the pericardial space approximately 2.5 cm in thickness. Both the visceral and parietal pericardium exhibited extensive scattered delayed hyperenhancement. Subsequent pericardial biopsy showed markedly fibrotic pericardium and pathology showed biphasic malignant pericardial mesothelioma. Immunosuppressive medications were stopped, and he underwent thoracentesis. After multidisciplinary discussions, he was started on nivolumab every two weeks and ipilimumab with a plan for surgery based on response to therapy. However, progressive symptoms and worsening constriction physiology led to palliative consultation and comfort care transition, with him dying shortly after. Discussion: Recurrent pericarditis and pericardial effusion, along with negative typical pericardial fluid studies, raised suspicion for a non-benign etiology. Multimodality imaging was employed and led to a pericardial biopsy. Constrictive pericarditis is an uncommon presentation of primary pericardial mesothelioma. Biphasic mesotheliomas from pleural or peritoneal origins are normally treated with systemic therapy with preference for combined immunotherapy. Primary pericardial mesothelioma is associated with a late presentation and high mortality rate, with surgery, if able to be done early appearing to be the recommended approach.

Paradoxical Improvement in Malignant Pleural Mesothelioma Outcomes Following Delayed Treatment Initiation

Paradoxical Improvement in Malignant Pleural Mesothelioma Outcomes Following Delayed Treatment Initiation

Impact of surgical intervention on overall survival in malignant pleural mesothelioma: A population-based cohort study with propensity score matching

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes. MethodsData from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases. ResultsThe study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9% and 11.2%, respectively, while for no-surgery patients, they were 34.9% and 3.7% (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95% CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades. ConclusionSurgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential.

Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.

Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM. An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies. NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice. NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

The Holy Grail of Long -Term Survival after Surgery for Malignant Pleural Mesothelioma

The Holy Grail of Long -Term Survival after Surgery for Malignant Pleural Mesothelioma

Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.

Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

Antigen targeting and anti-tumor activity of a novel anti-CD146 212Pb internalizing alpha-radioimmunoconjugate against malignant peritoneal mesothelioma

Malignant mesothelioma, a highly aggressive cancer that primarily affects the serosal membranes, has limited therapeutic options, particularly for cavitary tumors, such as peritoneal and pleural malignant mesothelioma. Intracavitary administration of a radioimmunoconjugate to locally target mesothelioma cancer cells has been proposed as a treatment. CD146, upregulated in mesothelioma but not in healthy tissues, is a promising therapeutic target. This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212Pb (212Pb-TCMC-OI-3) in human mesothelioma cells. Flow cytometry showed that both chimeric (chOI-3) and murine (mOI-3) antibodies rapidly bound and internalized within 1–6 h in MSTO-211H cells. 212Pb-TCMC-chOI-3 exhibited 3.1- to 13.7-fold and 3.1- to 8.5-fold increased internalized 212Pb and 212Bi atoms per cell at 2 and 24 h, respectively, compared to isotype control, underscoring enhanced internalization efficiency. Intraperitoneal administration of 212Pb-TCMC-mOI-3 to mice with intraperitoneal MSTO-211H xenografts improved median survival by a ratio of 1.3 compared to non-binding 212Pb-TCMC-mIgG1. The ability of 212Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy’s efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes.

The efficacy and safety of anlotinib combined with chemotherapy in treatment of advanced soft tissue sarcoma

BackgroundTo evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS).MethodsA total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles.ResultsAccording to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found.ConclusionsAnlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

Asbestos is still paid for dearly

Abstract Background In Italy, asbestos is a current and important problem in terms of health effects due to the long latency of diseases related to its exposure. The aim of the study is to analyze the case history of malignant pleural mesothelioma (MPM) in the University Hospital of Siena in the period 2019-2023, comparing the type of exposure (occupational/non-occupational), the mean conventional latencies (MCL) of diagnosis, the histotype and the most exposed categories. Methods The study was conducted from January to April 2024, on 69 patients (79.7% male and 20.3% female) with a diagnosis of pleural mesothelioma between 2019 and 2023. 48 patients lived in Tuscany and 21 outside the region. The data were collected by consulting the medical surveillance records and radiological images through the VuePacs platform, then organized in a filtered database. Results Of 69 patients, exposure was occupational in 54 cases and non-occupational in the remaining 15. In patients with occupational exposure, the MCL was 55.9 years and the mean age at diagnosis was 73.66 years; in the other group, the MCL was 47.3 years and the mean age at diagnosis was 66.8. The study revealed the prevalence of epithelioid histotype in 76.81% of cases, biphasic in 15.94% of cases and sarcomatoid in 7.25%. The most at-risk categories were: metalworking (10 cases), construction (8), electricity/gas production (6) and shipyards (4). The study also identified two cases of atypical occupational exposure. Conclusions The shorter average latency in cases with non-occupational exposure is in accordance with the current scientific literature, as well as the prevalence of epithelioid histotype. Are hereby confirmed the primary role of health surveillance in the in-depth investigation of occupational anamnesis and of the environmental sites’ survey as prevention tool, especially in those cases of MPM whose evaluation, deviating from the exposure standards, could lead to the assignment of a misdiagnosed exposure. Key messages • The effects of asbestos exposure are a current and important problem in our country, even after its disposal, due to the long latency of disease onset. • In-Department investigation of occupational anamnesis and survey of environmental sites as prevention tool play an essential role in MPM evaluation, especially in those cases of atypical exposure.

Surgical and oncological outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma : Aretrospective single center experience.

Peritoneal mesothelioma (PM) is arare disease with various histopathological subtypes. For malignant peritoneal mesothelioma and borderline subgroups locoregional therapy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been implemented. The aim of our study was to retrospectively present the outcome after CRS and HIPEC for patients with different subtypes of peritoneal mesothelioma. In total 15patients received CRS and HIPEC due to peritoneal mesothelioma at our tertiary referral hospital between 2013 and 2022. Surgical and oncologic outcomes of 14 of those patients were retrospectively evaluated as one patient was lost to follow-up. The cohort consisted of 9patients with diffuse malignant peritoneal mesothelioma (64.3%), 3patients with multicystic peritoneal mesothelioma (21.4%) and 2patients with well-differentiated peritoneal mesothelioma (14.3%). Complete cytoreduction was possible in 85.7% (n = 12). The major complication rate was 28.6% (n = 4) and the reoperation rate was 14.3% (n = 2). Median follow-up was 55months (standard error, SE 15.0%, 95% confidence interval, CI 25.6-84.4 months). Over this time period 64.3% (n = 9) had no evidence of disease, 21.4% (n = 3) were alive with disease and 14.3% (n = 2) died of peritoneal mesothelioma. The median recurrence-free survival of patients was 13months (SE13.0%, 95% CI 0.0-32.2 months). None of the patients with multicystic peritoneal mesothelioma had evidence of disease at the time of last follow-up. Patients with peritoneal mesothelioma should receive locoregional treatment as good oncological results can be achieved with reasonable postoperative morbidity. Thus, awareness is necessary for this rare but potentially aggressive disease to offer the best medical care.

An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).

Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.

Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

Confirmatory validation of a brief patient-reported outcome measure assessing psychological distress in caregivers of malignant mesothelioma patients: the Mesothelioma Psychological Distress Tool-Caregivers.

The diagnosis of malignant mesothelioma (MM) can be devastating for both patients and caregivers, who may experience intense suffering from a physical, psychological, and interpersonal perspective. Despite the extensive literature on caregiver distress, there is a lack of validated measures to provide evidence of psychological distress of caregivers of MM patients. Therefore, in a previous study we developed the Mesothelioma Psychological Distress Tool-Caregivers (MPDT-C) to evaluate the specific profile of psychological distress in this population. This paper describes the item selection, factor analysis, and psychometric evaluation of the revised MPDT-C. The analyses of this work first aimed to confirm the previous factorial structure. In the case of nonfit, it aimed to find an alternative structure and causes of nonfit in the model. Examination of the fit of the factorial model was conducted using a Bayesian approach. The final version of the MPDT-C is a 7-item self-report questionnaire consisting of one factor (Burden for the caregiver). Having a short self-report questionnaire to assess the psychological distress experienced by caregivers of MM patients has several advantages. First, it is suited to epidemiological studies where multiple variables and measures are involved. Second, it is easy to administer and does not take much time to complete. Therefore, the MPDT-C can also be administered in clinical contexts, perhaps when MM patients attend follow-up medical evaluation. Lastly, short measures are less affected by cognitive fatigue, which is very common in a long battery of tests and could affect response reliability.

Synergistic Effect of Resveratrol and Paclitaxel in the Treatment of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a lethal and aggressive cancer due to exposure to asbestos since this carcinogen is still being used in industrial buildings and housing in several countries. Untreated MPM has a median survival time of 12 months, and most people die within 24 months after diagnosis. If caught early, surgery may be performed. Treatment option for palliative care is limited using platinum with pemetrexed. Malignant transformation of a cell is attributed to a series of genetic and epigenetic events involving alterations in several oncogenes, tumor suppressor genes, and others. Different anticancer and antioxidants with anticancer properties were tested individually and in combination to find the best synergistic effect in killing MSTO-211H, a lung mesothelioma cell line used as model of MPM. Once the combination was identified, assays and staining methods such as MTT, Rhodamine123, Hoechst 33342, Nuclear ID Red/Green, and Western Blot were performed to identify different proteins involved in apoptosis and cell signaling cascade to proof the cytotoxic effect of the combine anticancer and antioxidant treatment. Combination of Paclitaxel (PAC) at 3 µM and Resveratrol (RSV) at 62.5 µM showed synergistic effect on MSTO-211H cells by causing inhibition of epidermal growth factor receptor (EGFR), inhibition of mitogen activated protein kinases (MEKs) 1-4, inhibition of programmed death ligand-1 (PDL-1), inhibition of cell cycle proteins, and induction of caspases 3-8. This study provided possible potential application of using RSV as a chemo-enhancing compound with PAC in the treatment of MPM.

Bedside to bench and back again-translational research in interventional pulmonology.

Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest. In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted. In pleural disease, less invasive/conservative treatment in pneumothorax, early aggressive treatment in pleural infection along with novel biomarkers, and the shift beyond drainage strategies in malignant pleural effusion and mesothelioma will be discussed. This overview of translational research in the field of interventional pulmonology will ultimately help to highlight the gaps in current evidence to promote research in areas of clinical significance.

P4.14C.04 Exhaled Breath Analysis for the Early Diagnosis of Malignant Pleural Mesothelioma and the Surveillance of Asbestos-Exposed At-Risk Subjects

P4.14C.04 Exhaled Breath Analysis for the Early Diagnosis of Malignant Pleural Mesothelioma and the Surveillance of Asbestos-Exposed At-Risk Subjects

Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.

Pleural mesothelioma (PM), a rare malignant tumor explicitly associated with asbestos and erionite exposures, has become a global health problem due to limited treatment options and a poor prognosis, in which the median life expectancy varies depending on the method of treatment. However, the importance of early diagnosis is emphasized, and the practical methods have not matured yet. This study provides a critical overview of PM, addressing various aspects like epidemiology, etiology, diagnosis, treatment options, and the potential use of advanced technologies like microfluidic chip-based models for research and diagnosis. It initially begins with fundamentals of clinical aspects and then discusses the identification of disease-specific biomarkers in patients' serum or plasma samples, which could potentially be used for early diagnosis. A detailed investigation of the sophisticated preclinical models is highlighted. Recent three-dimensional (3D) model accomplishments, including microarchitecture modeling by transwell coculture, spheroids, organoids, 3D bioprinting constructs, and ex vivo tumor slices, are discussed comprehensively. On-chip models that imitate physiological processes, such as detection chips and therapeutic screening chips, are assessed as potential techniques. The review concludes with a critical and constructive discussion of the growing interest in the topic and its limitations and suggestions.