scholarly journals The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma

2021 ◽  
Vol 28 (6) ◽  
pp. 4542-4552
Author(s):  
Shantanu Banerji ◽  
Daniel E. Meyers ◽  
Craig Harlos ◽  
David E. Dawe

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.

2015 ◽  
Vol 7 ◽  
pp. BIC.S25375 ◽  
Author(s):  
Adi Idris ◽  
Nur B. Ghazali ◽  
David Koh

The relationship between cancer and inflammation is a complex but intimate one. Decades of work has shown to us that cancer progression is influenced by a multitude of factors, including genetic, environmental, and immunological factors. We often overlook that cancer progression is also a pathological consequence of a dysregulated inflammatory control in the body. A current emerging topic in cancer research is the role of inflammasomes in carcinogenesis. The inflammasome is a multicomplex protein platform that when activated results in the release of proinflammatory cytokines, such as interleukin (IL)-1β. There is increasing evidence suggesting that IL-1β plays a pivotal role in cancer progression. This short review proposes the possibility of using IL-1β as a potential cancer progression biomarker and discusses the use of saliva as a model biological fluid for measuring physiological IL-1β levels in the body.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
F. Grosso ◽  
G. Rota ◽  
M. Dacquino ◽  
S. Crivellari ◽  
S. Delfanti ◽  
...  

Background: The study was aimed at exploring the patients’ and caregivers’ expectations on treatment outcomes, the understanding of the information delivered by the oncologists during the first and reevaluation visits and the role of the general practitioners (GP) in the management of patients suffering from advanced Malignant Pleural Mesothelioma (MPM) in the area of Casale Monferrato, in the North West of Italy, where the incidence of mesothelioma is more than 30 times higher than the median incidence in Europe. A multiprofessional mesothelioma unit involving specialists and also GPs has been created since 2012 to globally assist patients in each step of the diagnostic and therapeutic process. This study was conducted to better understand the need of MPM patients in our area and their satisfaction about the care provided within the unit. Methods: Patients and caregivers were asked to fill in a multiple-choice questionnaire after the first visit or the re-evaluation visits (the ones in which a new treatment program was communicated) asking what is most important as the result of treatment, how much the oncologist was clear in communicating the diagnosis, the therapeutic options, the side effects, the role of the GP in supporting the care process and the trust-relationship with both the referral oncologist and the GP. Patients were also asked about the importance of having a referral caregiver. Results: From March to August 2019, 31 consecutive patients, 18 males and 13 females, median age 71 (IQR 66-75) and 29 caregivers, 7 males and 22 females, median age 63 (IQR 49-67) were enrolled in the study. Improving survival was the most relevant expected outcome in 48% and 69% of patients and caregivers, respectively followed by maintenance of the quality of life (38% and 17%), having the minimal number of accesses in the hospital as possible (8% vs 4%) and improving symptoms (6% and 10%). Seventy-seven% of patients and 72% of caregivers stated that the communication of the diagnosis was very clear, 74% of patients and 72% of caregivers stated that explanations about treatments were very clear, 90% of both patients and caregivers stated that the communication of side effects was sufficiently clear. Ninety% of patients and 86% of caregivers are completely satisfied about the relationship with the referral oncologist whereas 58% of patients and 55% of caregivers are completely satisfied with the support given by the GP. Ninety-three% of patients think that having a referral caregiver is of utmost importance and 80% of patients appreciate the presence of a palliative expert in the patient-care team whereas 52% of patients think to require a psychological support. Conclusions: This study highlights that in the high incidence area of MPM of Casale Monferrato, only half of advanced MPM patients and less that 2/3 of caregivers think that improving survival is the most relevant treatment outcome. The majority of patients and caregivers state to have clear information about diagnosis, treatment and related side effects and feel satisfied about the relationship with the specialists of the mesothelioma unit.


2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.


2021 ◽  
pp. 097168582110159
Author(s):  
Sital Mohanty ◽  
Subhasis Sahoo ◽  
Pranay Kumar Swain

Science, technology and human values have been the subject of enquiry in the last few years for social scientists and eventually the relationship between science and gender is the subject of an ongoing debate. This is due to the event of globalization which led to the exponential growth of new technologies like assisted reproductive technology (ART). ART, one of the most iconic technological innovations of the twentieth century, has become increasingly a normal social fact of life. Since ART invades multiple human discourses—thereby transforming culture, society and politics—it is important what is sociological about ART as well as what is biological. This article argues in commendation of sociology of technology, which is alert to its democratic potential but does not concurrently conceal the historical and continuing role of technology in legitimizing gender discrimination. The article draws the empirical insights from local articulations (i.e., Odisha state in eastern India) for the understandings of motherhood, freedom and choice, reproductive right and rights over the body to which ART has contributed. Sociologically, the article has been supplemented within the broader perspectives of determinism, compatibilism alongside feminism.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Meilin Chan ◽  
Licun Wu ◽  
Zhihong Yun ◽  
Trevor D. McKee ◽  
Michael Cabanero ◽  
...  

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3061
Author(s):  
Francesca Aprile ◽  
Giovanni Bruno ◽  
Rossella Palma ◽  
Maria Teresa Mascellino ◽  
Cristina Panetta ◽  
...  

Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma–carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using “adenoma microbiota” and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium, Faecalibacterium, Bacteroides and Romboutsia. Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma’s endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.


2002 ◽  
Vol 29 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Edith M. Marom ◽  
Jeremy J. Erasmus ◽  
Harvey I. Pass ◽  
Edward F. Patz

Author(s):  
Alfonso Varela-López ◽  
Laura Vera-Ramírez ◽  
Francesca Giampieri ◽  
María D. Navarro-Hortal ◽  
Tamara Y. Forbes-Hernández ◽  
...  

2018 ◽  
Vol 67 (2) ◽  
pp. 338-345 ◽  
Author(s):  
Jianshuang Li ◽  
Tong Li ◽  
Shuo Li ◽  
Lipeng Xie ◽  
Yi-Lin Yang ◽  
...  

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.


1970 ◽  
Vol 2 (2) ◽  
pp. 25-31
Author(s):  
Samin Gheitasy ◽  
Leila Montazeri ◽  
Simin Dolatkhah

The dramatic text defines, to some extent, the structure of the work but the type of performance and the physical approach to the text can represent different meanings. The body of the actor, as a means of conveying concepts from the text to the audience, can be effective in creating different interpretations and meanings of the text. Since eons ago, directors have used the body of the actor with different approaches, and the application of body on the stage has always been underdoing changes. Anne Bogart is one of the few directors who is less known in the Iranian theater despite possessing the most updated and well-known methods of practice and performance in the world. Using her viewpoint method, she brings live and dynamic bodies to the stage; bodies that are able to convey the hidden meanings of the text to the audience in the most suitable way. The overall purpose of this research is to find the relationship between the dramatic text and the performance with the centrality of the body with a sociological view toward the body. To this end, by presenting Foucault's theories, the researchers defines the role of the body in the society and its extent of effectivity and impressibility. Finally, this study explores the implications of this role in each element of Aeschylus’s The Persians, and it shall show how Bogart beautifully represents them using the bodies of her actors during performance.


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