Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC.     

碘杂环化合物IHC-72、利多卡因及维拉帕米抗心律失常作用的比较

在大鼠和豚鼠整体模型上,比较观察了等毒剂量(1/ LD₅₀)的IHC-72、利多卡因和维拉帕米对乌头碱、哇巴因致心脏毒性的保护作用,以及对急性缺血再灌注心律失常和缺血心肌室颤阈的影响。IHC-72抗乌头碱致大鼠心脏毒性作用,与利多卡因相当,而比维拉帕米强;IHC-72抗哇巴因致豚鼠心脏毒性作用,与利多卡因相当而比维拉帕米弱;对提高大鼠缺血电室颤阈值的作用,IHC-72比利多卡因及维拉帕米弱;对预防大鼠急性缺血再灌注的心律失常作用,三者作用近似。     

赛庚啶对离体大鼠心脏缺钙/复钙损伤(钙反常)的保护作用

离体大鼠心脏经无钙灌流(灌流液为不含Ca²⁺的K-H液,通以95%O₂和5%CO₂的混合气体)5min后,用正常K-H液进行复钙灌流20min,可导致心肌细胞内酶(CPK,LDH)及蛋白的大量漏出,心脏变苍白,甚至出现心脏挛缩,心肌组织抗氧自由基酶(SOD,GSH-Px)活性明显降低,但MDA含量无明显改变。赛庚啶(2.5～5μmol/L)能明显减少心脏Ca²⁺反常时心肌组织内酶及蛋白的漏出,显著保护心肌组织抗氧自由基酶的活性。     

Nucleic acid composition of bone marrow mononuclear cells in cobalamin deficiency

Recent studies using anion exclusion chromatography have suggested that uracil is misincorporated into the DNA of patients with megaloblastic anemia to levels detectable by nonradioactive methods. We have investigated the nucleotide composition of DNA from the bone marrow mononuclear cells of eight patients with cobalamin deficiency and compared this with that found in normal subjects. The median level of uracil in the megaloblastic group was 0.082 mol% of cytosine (approx. 0.02 mol% of all bases in DNA), which was similar to that found in the control group (median 0.085 mol% of cytosine) and may be attributable, at least in part, to artefactual deamination of deoxycytidine monophosphate during the DNA hydrolysis. Our findings give no support for the view that, by overwhelming the uracil N-glycosidase mechanism, the degree of uracil misincorporation in megaloblastic anemia is sufficient to increase the steady state level of uracil in the DNA by amounts detectable by nonradioactive methods. Using high performance liquid chromatography, we have also demonstrated normal levels of methylcytosine in the DNA of megaloblastic subjects.