Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma

Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor–stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.

Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.

Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1–5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.

Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies.

Source: Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

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Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

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Source: Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study


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Lung-sparing surgery may boost mesothelioma survival

Surgery that preserves the lung, when combined with other therapies, appears to extend the lives of people with a subtype of the rare and deadly cancer mesothelioma, a new study suggests.

Tracking 73 patients with advanced malignant pleural mesothelioma—which affects the lungs’ protective lining in the chest cavity—researchers found that those treated with lung-sparing had an average survival of nearly three years. A subset of those patients survived longer than seven years.

Mesothelioma patients treated with chemotherapy alone, which is standard care, live an average of 12 to 18 months, the researchers said.

Study participants received lung-sparing surgeries and another treatment called photodynamic therapy that uses light to kill cancer cells. Ninety-two percent of the group also received chemotherapy.

The study volunteers achieved far longer survival times, said study author Dr. Joseph Friedberg.

“When you take the [entire] lung out, it’s a significant compromise in quality of life,” said Friedberg. He’s director of the University of Maryland Medical Center’s Mesothelioma and Thoracic Oncology Treatment and Research Center in Baltimore.

“For all intents and purposes, this [lung-sparing surgical approach] is the largest palliative operation known to man, since chances of curing mesothelioma are vanishingly small,” said Friedberg. He completed the research while at his previous post at the University of Pennsylvania.

“Plus, most of these patients are elderly, so preserving quality of life was really the goal,” he added.

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Source: Lung-sparing surgery may boost mesothelioma survival


 

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Justices OK Expert Opinion on Asbestos, Seeing No Breach of ‘Any Exposure’ Ban

Experts testifying in asbestos trials need not compare the exposure of one defendant’s products to a plaintiff’s overall exposure, the Pennsylvania Supreme Court ruled Nov. 22.

The majority reasoned that noncomparative testimony did not violate the ban against using “any exposure” causation theories.

The ruling affirmed the Superior Court’s decision, which upheld a $994,800 jury award out of the Philadelphia Court of Common Pleas.

Justice Christine L. Donohue, who wrote the majority opinion in Rost v. Ford Motor, said plaintiff Richard Rost’s expert properly testified that Rost’s exposure to the defendant’s asbestos-containing products was substantial and alone could have caused Rost to develop mesothelioma. Having the expert quantify and distinguish exposure to the defendant’s products and compare that to every other exposure Rost had would create a nearly impossible hurdle for plaintiffs that doesn’t exist in other tort cases, Donohue said.

“Multiple asbestos-containing products may be substantial factors causative of a plaintiff’s mesothelioma. It is for the finder of fact, and not the courts, to make these determinations regarding substantial causation,” Donohue said. “The dissenting justices’ concern about whether the jury could understand whether the bucket of water was placed in a bathtub or an ocean misses the mark entirely, since Dr. [Arthur] Frank testified that Rost’s exposures at Smith Motors [where Ford’s asbestos-containing products were used], without more, were sufficient to cause his cancer.”

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SourceJustices OK Expert Opinion on Asbestos, Seeing No Breach of ‘Any Exposure’ Ban


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Asbestos-related cancer won’t be overcome anytime soon, doctors say

New methods are giving doctors a better handle on diagnosing and treating asbestos-related cancers, but no cures are on the horizon.

“I think it would be overly optimistic to say it’s going to be cured. I mean we can always dream,” said oncologist Dr. Christopher Lee, an expert on mesothelioma.

Paul Demers, a senior scientist in prevention at the Occupational Cancer Research Centre in Toronto, said one of the difficulties in diagnosing mesothelioma is the long latency period — the period between exposure and the development of symptoms — which can sometimes be up to 40 years.

When asbestos fibres are inhaled or ingested, they become trapped in the pleural lining of the lungs. Over time, thousands of tiny fibres cause scarring in the tissue.

New equipment like the CyTOF instrument allows doctors to detect asbestos earlier and with more precision, which could facilitate more effective treatments for asbestos victims.

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Source: Asbestos-related cancer won’t be overcome anytime soon, doctors say


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Criminality and Asbestos in Industry

Criminal prosecutions of individuals in the asbestos industry are reviewed, particularly the case of asbestos owner-executive Stephan Schmidheiny. Italian courts sentenced Schmidheiny to sixteen to eighteen years in jail for creating an environmental disaster causing three thousand deaths. The convictions were overturned on a technicality, and a murder case against Schmidheiny has started. His firm, Eternit, made asbestos-cement building products in many countries. Schmidheiny directed a cover-up that the Italian Court of Appeal blamed for delaying the ban of asbestos in Italy by ten years. Today, the asbestos industry is a criminal industry, profiting only by minimizing its costs for the prevention and compensation of occupational and environmental illness. The asbestos industry should only be consulted by governments for the purpose of closing it and dealing with the legacy of in-place asbestos.

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Source: Criminality and Asbestos in Industry


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Malignant Mesothelioma in a Motor Vehicle Mechanic

Case reports remain an important source of data in the debate over the carcinogenic effect of asbestos-containing automotive friction products. This report documents a case of pleural mesothelioma accompanied by asbestos bodies in the lung tissue of a career auto mechanic with no other known sources of exposure. Previously unreported historical and contemporary exposure data are also discussed in the context of providing additional support for the proposition that work with asbestos-containing automotive products presents a risk of significant exposure. While there remains a body of negative epidemiology that fails to find an increased risk of disease among auto workers, those data must be approached with caution. Many of those studies have drawn technical criticisms, which are beyond the scope of this report, but they remain a key part of the legal defense mounted by defendant-companies who are involved in asbestos-related litigation. This ongoing debate provides the context for the continued relevance of case reports such as this one, as well as the presentation of new and previously unpublished exposure data.

Source: Malignant Mesothelioma in a Motor Vehicle Mechanic


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Deadly Remnants of Asbestos in Italy (photos slideshow)

Although Italy joined asbestos-producing nations in banning the carcinogenic material at the end of the 20th century, thousands of people working in factories and living in public housing had already been exposed. In other words, as the Italian photographer Cinzia Canneri explained, the damage had been done by the 1980s.

Ms. Canneri said it could take up to 30 years after exposure for diseases like asbestosis or mesothelioma to develop. As a result, large numbers of people in the last decade have begun to suffer in Italy and more are expected to — with few legal or medical protections.

“They have not been recognized as victims,” Ms. Canneri said through an interpreter. “They want to speak and be heard.

”To help them, Ms. Canneri spent the last two years closely following asbestos victims, documenting their daily lives and struggles as they deal with new diseases, mourn deceased family members, visit doctors and contemplate whether or not time is running out on their health.

[Article continues at original source]

Source: Deadly Remnants of Asbestos in Italy (photos slideshow)


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Boeing Can Take Asbestos Case to Federal Court Under Contractor Defense

The Boeing Co. is entitled to the military contractor defense from liability in a suit claiming it failed to warn of the dangers of asbestos, the U.S. Court of Appeals for the Third Circuit ruled on Tuesday.

The appeals panel reversed the decision of a U.S. district court judge in New Jersey who granted the plaintiff’s motion to send the case back to state court after Boeing removed it to federal court under the federal officer removal statute. Boeing is entitled to remove the case to federal court because it made the requisite showing that it engaged in the allegedly culpable behavior at the direction of a federal officer or agency, Third Circuit Judges Kent Jordan, Thomas Vanaskie and Cheryl Ann Krause ruled in Papp v. Fore-Kast Sales.

U.S. District Judge Peter Sheridan of the District of New Jersey granted the plaintiff’s motion to send the case back to state court upon finding that, as a contractor, it had a “special burden” to demonstrate that it was acting under federal government control. Sheridan said Boeing could only show it was acting under a federal officer by showing that was directly instructed by federal authority to keep mum about the dangers of asbestos.

Source: Boeing Can Take Asbestos Case to Federal Court Under Contractor Defense


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Is Asbestos Trial Consolidation Ending in Philadelphia

Defense attorneys have long said the practice of consolidating asbestos trials in Philadelphia gives the plaintiffs’ bar an unfair advantage, but some are now looking to a recent state Supreme Court decision as an indication that the consolidation of asbestos trials might be on its way out.

The practice of consolidating trials began more than 25 years ago in an effort to get control of a spiraling backlog of asbestos cases. Consolidation was credited with quickly wiping out the backlog and became the standard for how asbestos cases would be tried in Philadelphia.

Nearly five years ago, however, the court eliminated mandatory consolidation and placed a limit on the number of cases that could be consolidated into a single trial. Since then, the number of asbestos cases being tried to verdict has been decreasing, which attorneys attributed to growing success with mediation. Of the cases that go to trial, thought, many are still consolidated.

However, according to defense attorneys, the Supreme Court’s recent decision in Rost v. Ford Motor might help the defense bar in its efforts to challenge consolidation.

Source: Is Asbestos Trial Consolidation Ending in Philadelphia


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