Duodenal adenocarcinoma is a rare digestive cancer, often diagnosed at a late stage and harbours a poor prognosis. The arrival of immunotherapy has changed the prognosis of many neoplasia, including ...digestive adenocarcinomas with MSI-H status. Hereby, we describe three cases of MSI-H locally advanced duodenal adenocarcinoma who received neoadjuvant treatment with a PD1 inhibitor, pembrolizumab. A partial metabolic and endoscopic response was observed in all patients after 2 cycles. Duodenopancreatectomy was performed at the end of treatment (4–6 cycles), and anatomopathological analysis demonstrated pathological complete response in all patients. Our case series paves the way for prospectively exploring neoadjuvant immunotherapy in duodenal MSI-H adenocarcinoma and raises the question of organ sparing surgery in case of complete clinical response as observed in gastric and colo-rectal adenocarcinomas.
•Duodenal adenocarcinoma is rare cancer with poorly defined standard therapies.•Immune checkpoint inhibitors have changed management of MSI-H tumours.•Neoadjuvant immunotherapy may lead to pathological complete response.•Our observation paves the way to further explore organ sparing surgery.
Computing is experiencing a “Cambrian explosion” of new technologies that promise great societal benefits but also create opportunities for misuse and societal harm. How to reduce this potential for ...harm is the objective of computing codes of ethics. Given the rash of ethical lapses related to computing, we ask whether codes of ethics are effective and, if not, why not?
More disgruntled customers are filing lawsuits against vendors when their IT projects go bad, typically alleging the vendors didn't live up to their promises. Courts, however, routinely dismiss these ...lawsuits, citing "vendor puffery." This article examines puffery, and how to avoid being persuaded by it to one's regret.
For 75 years, the basic measure of computing success has been focused on improving information technology's (IT) technical know-how. Concerns about whether that know-how was being used fairly and ...ethically was a remote afterthought. Emerging technical know-how and its potential for genuinely harmful misuse demand that the fair and ethical use of IT must be intimately tied to the concept of success.
Several decades' worth of internal and external audits of failed government IT modernization efforts suggest that a legislative solution is wishful thinking. It's time to examine the organizational ...dynamics and behavioral motivations underlying the problem.
Knowingly launching a flawed IT system that could harm society's most vulnerable as collateral damage isn't just callous - it's administratively evil. Any IT professional should be ashamed to be part ...of such a project.
Winning and Losing in IT Charette, Robert N.; King, John Leslie
Computer (Long Beach, Calif.),
10/2018, Letnik:
51, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The idea of winning and losing in IT raises questions about what these terms really mean for the "real world." Simple metrics such as market capitalization, patents granted, profit generated, level ...of market penetration, safety, and liability are increasingly accompanied by the more complicated issues of environmental impact, diversity, civil rights, and social justice. Engineers are increasingly called upon to consider such factors and effects in their work. This special issue explores the kinds of issues that arise when considering what it means to win or lose in IT.
Ras activation is a frequent event in human hepatocarcinoma that may contribute to resistance towards apoptosis. Salirasib is a ras and mTOR inhibitor that induces a pro-apoptotic phenotype in human ...hepatocarcinoma cell lines. In this work, we evaluate whether salirasib sensitizes those cells to TRAIL-induced apoptosis. Cell viability, cell death and apoptosis were evaluated in vitro in HepG2, Hep3B and Huh7 cells treated with DMSO, salirasib and YM155 (a survivin inhibitor), alone or in combination with recombinant TRAIL. Our results show that pretreatment with salirasib sensitized human hepatocarcinoma cell lines, but not normal human hepatocytes, to TRAIL-induced apoptosis. Indeed, FACS analysis showed that 25 (Huh7) to 50 (HepG2 and Hep3B) percent of the cells treated with both drugs were apoptotic. This occurred through activation of the extrinsic and the intrinsic pathways, as evidenced by a marked increase in caspase 3/7 (five to ninefold), caspase 8 (four to sevenfold) and caspase 9 (eight to 12-fold) activities in cells treated with salirasib and TRAIL compared with control. Survivin inhibition had an important role in this process and was sufficient to sensitize hepatocarcinoma cells to apoptosis. Furthermore, TRAIL-induced apoptosis in HCC cells pretreated with salirasib was dependent on activation of death receptor (DR) 5. In conclusion, salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis by a mechanism involving the DR5 receptor and survivin inhibition. These results in human hepatocarcinoma cell lines and primary hepatocytes provide a rationale for testing the combination of salirasib and TRAIL agonists in human hepatocarcinoma.
The STEM Anxiety Business Charette, Robert N.
Computer (Long Beach, Calif.),
2016-Mar., 2016-3-00, 20160301, Letnik:
49, Številka:
3
Journal Article
Recenzirano
Let's take a deep breath and stop the overwrought talk about a STEM crisis and how it's leading to the end of the American way of life as we know it. If current trends hold, we'll have more than ...enough STEM professionals to fill the available jobs for years to come.
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