冷冻干燥法制备阿糖胞苷冻干脂质体粉针研究

本文采用冷冻干燥法制备阿糖胞苷冻干脂质体粉针，并建立了质量控制标准。在扫描电镜和透射电镜观察下，将此脂质体冻干品加注射用水溶解后，能很快重新形成脂质体。算术平均粒径为０．４７５６±０．０８３３μｍ，包封率约３０％。     

Inhibition of Intestinal Pyrimidine Nucleoside Phosphorylases

The activity of 5-deoxy-5-fluorouridine (dFUR) depends on its activation to 5-fluorouracil (FU) by pyrimidine nucleoside phosphorylases. These enzymes are found in tumors and normal tissues, with the highest activity in the small intestines. The present study examined the inhibition of dFUR phosphorolysis in intestinal tissues. dFUR metabolism in intestinal homogenates was inhibited by uracil (U), uridine (UR), and thymidine (TdR), which are the normal substrates for the phosphorylases. Conversely dFUR reduced the metabolism of these inhibitors. A good agreement was found between the observed data and the computer-fitted data using the equations for competitive inhibition between dFUR and the inhibitors. In the absence of inhibitors, the V _max of dFUR phosphorolysis was 47.1 ± 4.9 µM/min and the apparent K _m was 910 ± 167 µM. The V _max was unaltered by the inhibitors, while the K _m was increased with increasing inhibitor concentrations. The maximal inhibition of dFUR metabolism by UR and TdR was about 80%. The K _i,'s were 372 µM for U, 87.2 µM for UR, and 112 µM for TdR and are orders of magnitude higher than their reported endogenous serum concentrations. The rate of dFUR phosphorolysis to FU in the intact intestinal epithelial crypt cells, indicated by the ratio of FU to dFUR in the intracellular fluid, was reduced by UR in a concentration-dependent fashion. These data indicate that the naturally occurring pyrimidines inhibit competitively the dFUR metabolism by the intestinal phosphorylases, that this inhibition occurs at concentrations much higher than the circulating endogenous levels, and that phosphorolysis is the major route of dFUR metabolism.     

以大剂量阿糖胞苷为主的联合化疗在儿童急性白血病中的应用

目的 :探讨大剂量阿糖胞苷 ( HDAC)治疗儿童急性白血病的效果和不良反应。　方法 :应用 HDAC治疗 3例急性髓细胞白血病 (每次 2 .0 g/m2 ,每 12 h1次 ,共 6次为一个疗程 )和 4例高危型急性淋巴细胞白血病 (每次1.0 g/m2 ,每 12 h1次 ,共 8次为一个疗程 )共 16个疗程 ,九个疗程在 HDAC结束后使用惠尔血 ( 2～ 3μg/kg)皮下注射 ,连续 10～ 14天。　结果 :6例按计划完成 HDAC治疗 ,并继续用常规方案治疗者 ,在 2 0～ 42个月的随访期内无病生存 ,1例 AL L- L3型在一个疗程 HDAC后出现中枢神经系统白血病复发 ,骨髓仍缓解 ,7个月后放弃治疗 .骨髓严重抑制和感染是最主要的不良反应 ,加用惠尔血可使粒细胞缺乏的持续时间缩短 ,感染发生率降低。　结论 :以 HDAC为主的联合化疗方案可安全地用于儿童急性白血病的强化治疗 ,对降低复发、提高无病生存率有积极意义     

3种细胞因子在体外对阿糖胞苷细胞毒性的影响

采用对碘硝基四唑（ＩＮＴ）比色法,观察了１７例急性髓性白血病（ＡＭＬ）患者和８例正常人的骨髓,在体外对阿糖胞苷的敏感性,同时分别观察了粒细胞集落刺激因子（Ｇ－ＣＳＦ）,粒－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）,白细胞介素－３（ＩＬ－３）３种细胞因子对其敏感性影响。结果显示ＡＭＬ细胞与正常细胞对Ａｒａ－Ｃ敏感性存在显著差异;Ｇ－ＣＳＦ,ＧＭ－ＣＳＦ,ＩＬ－３此３种因子均能增加Ａｒａ－Ｃ对ＡＭＬ细胞的     

Ras oncogene-transformed and nontransformed cell populations are each heterogeneous but respond differently to the chemotherapeutic drug cytosine arabinoside (Ara-C)

 In order to determine whether the growth of ras oncogene-transformed cells and nontransformed cells was inhibited differently by the chemotherapuetic drug cytosine arabinoside (Ara-C) their growth was analyzed by a novel colony-based assay that is sensitive and appropriate for heterogeneous cell populations. Colonies of nontransformed NIH3T3 cells, or ras onco- gene-transformed NIH(ras) cells, were grown in the absence of drug and then divided into subclones. Subclones were allowed to continue to grow in the absence or presence of drug. Growth inhibition was determined by comparing the growth of drug-treated subclones with the growth of related untreated subclones. Colonies of nontransformed cells grown in the absence of the drug displayed a large variation in growth, and when grown in the presence of the drug displayed a large variation in growth inhibition. Colonies of transformed cells also displayed a large variation in the absence and presence of the drug. For each cell line, related subclones were more similar to each other than to unrelated subclones, implying inheritance of growth rates and drug response. For NIH3T3 cells, the growth of subclones in the presence of drug was highly correlated with the growth of related subclones in the absence of drug. However, for NIH3T3(ras) cells the growth of subclones in the presence of drug was not correlated with the growth of related subclones in the absence of drug. Therefore, ras oncogene-transformed and nontransformed cell populations differ in their response to Ara-C. Received: 3 November 1995/Accepted: 30 July 1996     

补骨脂化学成分的研究

目的:对补骨脂的化学成分进行研究.方法:运用硅胶柱层析、Sephadex LH-20柱层析等手段进行分离,运用UV、IR、1HNMR、13CNMR、MS等波谱方法进行结构鉴定.结果:共分离鉴定了7个化合物,分别为异补骨脂素(isopsoralen,1),补骨脂素(psoralen,2),补骨脂定(psoralidin,3),补骨脂查耳酮(bavachalcone,4),补骨脂二氢黄酮(bavachin,5),大豆苷(daidzin,6)和尿嘧啶(uracil,7).结论:化合物6和7为首次从补骨脂属植物中分离得到.     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Effect of Granulocyte Colony-Stimulating Factor on Chemotherapeutic Activity of Cytosine Arabinoside in Acute Leukemic Cell Lines

Recent studies have shown the presence of receptors for granulocyte colony-stimulating factor (G-CSF) on lymphoid leukemic cells. To determine the effect of G-CSF on chemotherapeutic activity of cytosine arabinoside (Ara-C) on lymphoid as well as myeloid leukemic cells, we evaluated cell counts, apoptosis, and growth inhibition in HL-60, KG-1, Molt-4, Jijoye, and CCRF-CEM cell lines after incubation with Ara-C (0.1 and 1 micromol/L) and/or 5 ng/mL G-CSE G-CSF potentiated the effect of Ara-C on 2 of 3 lymphoid leukemic cell lines (Molt-4 and Jijoye), whereas it decreased the apoptosis and the effect of Ara-C on myeloid cell lines (HL-60 and KG-1).     

Induction of a hematological and cytogenetic remission in a patient with a myelodysplastic syndrome secondary to Fanconi's anemia employing the S-HAM regimen

 We report on a patient with Fanconi's anemia (FA) who developed a myelodysplastic syndrome (RAEB-T) with complex karyotypic abnormalities (trp 1q23 q 42, monosomy 20, trisomy 13) at the age of 28. The patient achieved a complete hematological and cytogenetic remission after treatment with sequential high-dose cytosine arabinoside/mitoxantrone followed by G-CSF (5 μg/kg). Bone marrow hypoplasia was prolonged with 38 days of granulocytopenia <500/μl and 62 days of platelet transfusion dependency. Nonhematological toxicity did not exceed that of patients without underlying FA. Remission duration was 7 months. This observation shows the feasibility of high-dose Ara C treatment in patients with FA and MDS. Although hematopoiesis remained clonal in remission, the suppression of the cytogenetically abnormal clones transiently reversed the antecedent long-lasting pancytopenia. Received: 16 September 1996 / Accepted: 27 January 1997     

Methotrexate myelopathy with extensive transverse necrosis: Report of an autopsy case

The patient was a 70‐year‐old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara‐C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo‐sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara‐C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient.