Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although Europe, Canada and the US have switched from cellular to acellular pertussis vaccines, most developing countries will continue to use the more cost effective cellular vaccine. Consistency of production however is the typical problem inherent to cellular vaccines. Optimising the production process of cellular pertussis bulk suspensions using product potency as a measure is not possible, since the mandatory animal test to measure potency has little discriminatory power. To circumvent this problem, this study focussed on measuring process parameters related to consistency and potency instead, even though the extent of those relationships could not be quantified. Critical evaluation and modification of individual process steps lead to 2 optimised production processes, NVP-96 and NVP-THIJS. These were compared to the original NVP production process in terms of antigen and biomass content, potency, toxicity and immunogenicity in mice. The batch to batch variation for both optimised products was clearly less than the original product for all parameters tested. The biomass content of the NVP-THIJS product was 15% lower than that of the NVP-96 product, while the immunogenicity in mice was twofold to threefold higher. The stability of the NVP-THIJS product remained higher than the NVP-96 product over a period of 2 years, while the decline of the potency of both suspensions was comparable.
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PMID:Improving the cellular pertussis vaccine: increased potency and consistency. 1815 25

Pancreatic cancer is an aggressive and devastating disease characterized by invasiveness, rapid progression and profound resistance to treatment. Despite years of intense investigation, the prognosis of this type of cancer is poor and there is no efficacious treatment to overcome the disease. Using human PANC-1 and MIA PaCa-2 cells, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) increases pancreatic cancer cell migration and invasion. Treatment of these cells with selective inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt1, or mammalian target of rapamycin 1 (mTOR1), or with specific siRNAs to silence the genes encoding these kinases, resulted in potent inhibition of C1P-induced cell migration and invasion. Likewise, the extracellularly regulated kinases 1 and 2 (ERK1-2), and the small GTPase RhoA, which regulates cytoskeleton reorganization, were also found to be implicated in C1P-stimulated ROCK1-dependent cancer cell migration and invasion. In addition, pre-treatment of the cancer cells with pertussis toxin abrogated C1P-induced cell migration, suggesting the intervention of a Gi protein-coupled receptor in this process. Pancreatic cancer cells engineered to overexpress ceramide kinase (CerK), the enzyme responsible for C1P biosynthesis in mammalian cells, showed enhanced spontaneous cell migration that was potently blocked by treatment with the selective CerK inhibitor NVP-231, or by treatment with specific CerK siRNA. Moreover, overexpression of CerK with concomitant elevations in C1P enhanced migration of pancreatic cancer cells. Collectively, these data demonstrate that C1P is a key regulator of pancreatic cancer cell motility, and suggest that targeting CerK expression/activity and C1P may be relevant factors for controlling pancreatic cancer cell dissemination.
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PMID:Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells. 2670 1