Study links BAP1 protein to tumor suppression in kidney, eye, bile duct and mesothelioma cancers

Researchers have shown how BRCA-associated protein 1 (BAP1) serves as a tumor suppressor gene in kidney, eye, bile duct, mesothelioma and other cancers by regulating a form of cell death called ferroptosis, opening up a potential new area of therapy research. (Mehr in: Cancer News — ScienceDaily)

Combination immunotherapy improves survival in mouse models of mesothelioma

Investigators have found that combined treatment with two cancer immunotherapy drugs — one a novel immune modulator and one that focuses and activates the anti-tumor immune response — significantly prolonged survival in mouse models of the aggressive cancer malignant mesothelioma. (Mehr in: Cancer News — ScienceDaily)

Mesothelioma: Why asbestos is so dangerous

Long, pointed asbestos fibers induce chronic inflammation, which can lead to cancer. Researchers have found underlying mechanisms for this and hope their results will help prevent damage. (Mehr in: Cancer News — ScienceDaily)

Rare genetic cause of peritoneal mesothelioma points to targeted therapy

Investigators have uncovered a new genetic cause of mesothelioma: a genetic rearrangement in the ALK gene, observed in three patients with peritoneal mesothelioma. Unlike previously known causes, this new discovery points to a potential therapeutic approach for those few patients whose tumors harbor the mutation. (Mehr in: Cancer News — ScienceDaily)

First immunotherapy for mesothelioma on the horizon, early research suggests

Malignant pleural mesothelioma or MPM is a rare cancer, but its incidence has been rising. This cancer is usually associated with asbestos exposure, and patients have a median life expectancy of only 13-15 months. All patients relapse despite initial chemotherapy, more than 50% of them within six months after stopping treatment. There are currently no effective therapeutic options for patients with MPM. (Mehr in: Cancer News — ScienceDaily)

Mesothelioma: New trial to fight cancer caused by asbestos

Patients with a hard-to-treat type of cancer are being given new hope in a ground-breaking clinical trial. (Mehr in: Cancer News — ScienceDaily)

Pembrolizumab shows promise in treatment of mesothelioma

Pembrolizumab, an antibody drug already used to treat other forms of cancer, can be effective in the treatment of the most common form of mesothelioma, according to a new study. The work is the first to show a positive impact from checkpoint inhibitor immunotherapy drugs on this disease. (Mehr in: Cancer News — ScienceDaily)

Active agent from the Caribbean sea cucumber could improve treatment for malignant pleural mesothelioma

Researchers have discovered a new option for treating malignant pleural mesothelioma. For the first time in the world, they were able to show in a preclinical study, both in the cell culture and in the animal model, that trabectedin, a chemotherapy drug that is already successfully used for other types of cancer, is also effective against malignant pleural mesothelioma. The active agent originally occurs in the Caribbean sea cucumber, a marine-dwelling tunicate. (Mehr in: Cancer News — ScienceDaily)

Mesothelioma surgery improves quality of life, study finds

Many mesothelioma patients avoid surgery for fear it will degrade their quality of life. But a study has found just the opposite: Patients who underwent an operation called pleurectomy and decortication (PD) generally reported their quality of life improved after surgery. (Mehr in: Cancer News — ScienceDaily)

Study suggests improvements in how mesothelioma is staged

A new study suggests that significant improvements could be made in the scoring system physicians use to estimate the stage (severity) of mesothelioma, an aggressive and deadly cancer. (Mehr in: Cancer News — ScienceDaily)

Statistical model may identify patients most likely to benefit from surgery for mesothelioma

A new statistical model may help predict which patients are most likely to receive life-extending benefits from surgical treatment for malignant pleural mesothelioma, scientists say. (Mehr in: Cancer News — ScienceDaily)

The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats

Non-neoplastic histopathological findings in the abdominal cavity. A: High-power view of anti-podoplanin immunohistochemistry showing single MWCNT A (high dose) nanotubes in the tissue (arrows). B: High-power view of anti-podoplanin immunohistochemistry showing single asbestos fibers in the tissue (arrows). C: H & E, high-power view of granuloma induced by MWCNT A (low dose) nanotubes including single nanotube (arrow, 25×). D: H & E, high-power view of granuloma induced by asbestos including single fiber (arrow, 40×). Rittinghausen et al. Particle and Fibre Toxicology 2014 11:59   doi:10.1186/s12989-014-0059-z
Non-neoplastic histopathological findings in the abdominal cavity. A: High-power view of anti-podoplanin immunohistochemistry showing single MWCNT A (high dose) nanotubes in the tissue (arrows). B: High-power view of anti-podoplanin immunohistochemistry showing single asbestos fibers in the tissue (arrows). C: H & E, high-power view of granuloma induced by MWCNT A (low dose) nanotubes including single nanotube (arrow, 25×). D: H & E, high-power view of granuloma induced by asbestos including single fiber (arrow, 40×).
Rittinghausen et al. Particle and Fibre Toxicology 2014 11:59 doi:10.1186/s12989-014-0059-z

Susanne Rittinghausen, Anja Hackbarth, Otto Creutzenberg, Heinrich Ernst, Uwe Heinrich, Albrecht Leonhardt and Dirk Schaudien

Abstract

Background

Biological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods.

Methods

A total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 109 or 5 × 109 WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (108 WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans.

Results

Treatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D – the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis.

Conclusion

We showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.

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