Pseudo-opioid resistant pain

The purpose of this article is to describe and analyse factors that result in pseudo-opioid-resistant pain. This is defined as a persistent pain experience communicated by the patient or family after prescription and initiation of opioid therapy based on empirically validated criteria. Pseudo-opioid-resistant pain can be caused by inadequate self-care or family care in relation to opioid therapy. Problems can arise in relation to communication of the pain experience, acceptance of the treatment choice and correct opioid administration. These problems may result from misconceptions or knowledge deficit, lack of motivation and lack of performance capabilities. The article systematically analyses the three categories of aetiological factors and arrives at a comprehensive explanatory model. This can be used for research purposes as well as for problem detection in clinical practice. The article includes a case report

Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin

Purpose: To assess efficacy of the novel, selective poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor AZD2281 against newly established BRCA2-deficient mouse mammary tumor cell lines and to determine potential synergy between AZD2281 and cisplatin. Experimental Design: We established and thoroughly characterized a panel of clonal cell lines from independent BRCA2-deficient mouse mammary tumors and BRCA2-proficient control tumors. Subsequently, we assessed sensitivity of these lines to conventional cytotoxic drugs and the novel PARP inhibitor AZD2281. Finally, in vitro combination studies were done to investigate interaction between AZD2281 and cisplatin. Results: Genetic, transcriptional, and functional analyses confirmed the successful isolation of BRCA2-deficient and BRCA2-proficient mouse mammary tumor cell lines. Treatment of these cell lines with 11 different anticancer drugs or with gamma-irradiation showed that AZD2281, a novel and specific PARP inhibitor, caused the strongest differential growth inhibition of BRCA2-deficient versus BRCA2-proficient mammary tumor cells. Finally, drug combination studies showed synergistic cytotoxicity of AZD2281 and cisplatin against BRCA2-deficient cells but not against BRCA2-proficient control cells. Conclusion: We have successfully established the first set of BRCA2-deficient mammary tumor cell lines, which form an important addition to the existing preclinical models for BRCA-mutated breast cancer. The exquisite sensitivity of these cells to the PARP inhibitor AZD2281, alone or in combination with cisplatin, provides strong support for AZD2281 as a novel targeted therapeutic against BRCA-deficient cancers