奥沙利铂联合方案治疗晚期胃癌的临床疗效

目的　研究奥沙利铂(L OHP)与氟尿嘧啶(5 FU)、亚叶酸钙(CF)联合化疗方案治疗晚期胃癌的近期疗效及不良反应。方法　2 0 0 2年6月至2 0 0 4年6月2 4例晚期胃癌患者入组本次临床试验。入组病例接受L OHP联合5 FU及CF治疗方案:d1,L OPH 130mg·m-2 ,ivgtt;d1～5 ,CF 2 0 0mg·m-2 ,ivgtt;d1～5 ,5 FU 5 0 0mg·m-2 ,ivgtt×6h ,2 1d为一个周期,至少完成3周期。分别观察其近期疗效及不良反应。结果　近期疗效判定参照WHO实体瘤疗效评价标准;不良反应按实体瘤(1981年)NCI分级标准。全组2 4例患者总有效率(CR +PR)为5 0 % (12 / 2 4 ) ;主要不良反应为轻度骨髓抑制、消化道反应及外周神经毒性。结论　L OHP联合化疗方案治疗晚期胃癌疗效确切,不良反应能耐受     

HPLC法测定丹参类注射液中4种水溶性成分含量

目的采用HPLC法同时测定香丹注射液 (复方丹参注射液 )及丹参注射液中 4种水溶性成分丹酚酸B、迷迭香酸、丹参素和原儿茶醛含量。方法采用HypersilC18(2 5 0mm× 4 6mm ,5 μm)色谱柱 ;以甲醇 水 二甲基甲酰胺 冰醋酸为流动相梯度洗脱 ;流速为 1 0mL/min ;柱温为 35℃ ;检测波长 2 80nm。结果丹参素、原儿茶醛、迷迭香酸和丹酚酸B线性范围分别在 0 0 194～0 194 0 g·L-1、0 0 0 4 0 4～ 0 0 4 0 4 g·L-1、0 0 0 80 8～ 0 0 80 8g·L-1和 0 0 2 6 0～ 0 2 6 0 0 g·L-1内 ,线性关系良好 (r≥ 0 9998) ;加样回收率分别为 10 4 % ,98 3% ,10 1% ,10 3% ,RSD <2 0 %。结论本研究为丹参类注射液的质量综合评价和控制提供了简单、准确、可行的分析方法。     

A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma

Abstract.   Valerio MR, Tagliaferri P, Raspagliesi F, Fulfaro F, Badalamenti G, Arcara C, Cicero G, Russo A, Venuta S, Guarneri G, Gebbia N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 79–85
We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m²), pegylated liposomal doxorubicin (30 mg/m²), and cyclophosphamide (750 mg/m²). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1–2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1–2 in 19 patients (48%). Twenty-one (53%) patients experienced grade 1–2 peripheral neuropathy. The overall response rate was 46% (95% CI 23.6–68.7). Median progression-free survival was 28 weeks (range 12–52 weeks) and median survival was 45 weeks (range 26–136+ weeks). The mean duration of response was 34 weeks (range 16–52 weeks). In platinum-resistant and -refractory ovarian cancer patients, the overall response rate was 37% (CI 95% 14.4–60.8) with a progression-free survival of 28 weeks (range 12–52 weeks) and a median survival of 42 weeks (range 28–84 weeks). This combination chemotherapy is generally well tolerated and is an active second-line regimen against ovarian cancer.     

含草酸铂方案治疗晚期贲门癌的疗效观察

目的观察草酸铂(L-OHP)联合5-氟脲嘧啶(5-Fu)、亚叶酸钙(CF)治疗晚期贲门癌的疗效与毒性。方法L-OPH135mg/m2ivgttD1,5-Fu350mg/m2ivgttD2-6,CF100mg/m2D2-6,21d为1周期。结果全组患者获得CR4例,PR12例,NC10例,PD4例,总有效率(CR+PR)为53.3%;骨髓抑制和胃肠道反应均为0-II°,80%患者出现外周感觉神经异常。结论该方案治疗晚期贲门癌疗效高,副作用少,值得临床应用。     

Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first-line treatment in advanced colorectal cancer: a multicenter, randomized, phase II study.

BACKGROUND: Irinotecan (IRI) and oxaliplatin (OXA) are effective in the treatment of colorectal cancer. Previously untreated patients with advanced colorectal carcinoma (CRC) were randomly assigned to receive IRI plus leucovorin (LV)/5-fluorouracil (5-FU), or OXA plus LV/5-FU in order to compare the response rates, time-to-tumor progression, overall survival rates, and toxicity profiles of these two agents. MATERIALS AND METHODS: From January 1999 to February 2002, 295 patients were randomized to receive either IRI/LV/5-FU or OXA/LV/5-FU. The treatment schedules consisted of weekly IRI 70 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) followed immediately by intravenous bolus 5-FU 450 mg/m(2) for 6 weeks, followed by a 2-week rest period. Treatment was continued for up to four cycles or until disease progression, unacceptable toxicity or patient refusal. RESULTS: There were no significant differences between the study arms in the overall response rate (33% with IRI/LV/5-FU versus 32% with OXA/LV/5-FU based on responses demonstrated on a single evaluation; 23% with IRI/LV/5-FU versus 22.3% with OXA/LV/5-FU based on responses confirmed according to WHO criteria) median time to progression (8.9 versus 7.6 months), and median overall survival (17.6 versus 17.4 months). Toxicity profiles (grades 3 and 4) were similar in the IRI and OXA arms (diarrhea 12.3% and 9.8%, neutropenia 8.2% and 4.9%, and febrile neutropenia 1.4% and 1.4%, respectively), with the exception of grade 3 sensory neuropathy, which almost exclusively occurred in the OXA arm (0% versus 5.6%; P=0.003, Fisher's exact test). CONCLUSION: The IRI/LV/5-FU and OXA/LV/5-FU regimens demonstrated equally substantial efficacies and manageable toxicity profiles in the first-line treatment of patients with advanced CRC. However, IRI/LV/5-FU may be the preferable regimen to avoid significant neurotoxicity associated with OXA-LV/5-FU.     

奥沙利铂联合卡培他滨治疗体力状况削弱的晚期胃癌临床观察

为了评估奥沙利铂联合卡培他滨治疗体力状况削弱的(KPS≤70)晚期胃癌的毒性和疗效,应用奥沙利铂联合卡培他滨治疗21例晚期胃癌患者。奥沙利铂100mg/m2,静脉滴入,持续3h,d1;卡培他滨1650mg/(m2·d),分2次口服,d1~d14;21d为1个周期。患者每2个周期行CT检查以评估疗效,并监控其毒性。结果:所有患者均可评估毒性,21例中有20例可评估疗效。PR6例(30%),SD8例(40%),PD6例(30%),有效率为30·0%。中位进展时间4·5个月,中位生存时间8·3个月。初步研究结果提示:奥沙利铂联合卡培他滨治疗体力状况削弱(KPS≤70)的晚期胃癌有效,且有良好的耐受性。     

拟康氏木霉胞外多糖联合奥沙利铂可体外协同抑制结直肠癌细胞的增殖

目的 探讨拟康氏木霉胞外多糖（EPS）联合奥沙利铂（Oxa）用药对结肠癌细胞HCT116的协同抑制作用。方法 实验分为Control组（0 μg/mL）、Oxa组（8 μg/mL Oxa）、EPS组（100 μg/mL EPS）、EPS+Oxa组（8 μg/mL Oxa+100 μg/mL EPS）。CCK-8检测细胞活力，CompuSyn软件拟合Fa-CI曲线评价联用效果。流式检测凋亡和周期、划痕实验和transwell实验检测细胞迁移能力，Oxa和EPS相关基因与结直肠癌相关基因取交集进行PPI分析以及GO和KEGG富集分析。结果 Oxa单用或与EPS联用处理HCT116细胞，均可使HCT116细胞活力受到抑制，并呈现剂量与时间依耐性，两者联用有明显的协同作用（CI<1）。两药联用组的细胞总凋亡率与Oxa组以及对照组比较均显著升高（P<0.05）；联合用药组处于S期的比例高于其他各组。EPS和Oxa均具有抑制HCT116细胞迁移的作用，两者联用后抑制作用更为明显。KEGG分析显示主要涉及耐药、凋亡、血管新生等通路。结论 EPS联合奥沙利铂可协同抑制HCT116细胞增殖，促进该细胞凋亡和细胞S周期阻滞、抑制细胞迁移，铂耐药、PI3K-Akt、MAPK等信号通路发挥了关键作用。     

Cell layers and neuropil: contrast‐enhanced MRI of mouse brain in vivo

Contrast‐enhanced T₁‐ and T₂‐weighted MRI at 9.4 T and in‐plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁‐weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd‐DTPA) reflects the extra‐ and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂‐weighted MRI, but offers a 16–30‐fold higher contrast‐to‐noise ratio. Systemic administration of manganese chloride increases the signal‐to‐noise ratio in T₁‐weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium‐enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium‐enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities. Copyright © 2013 John Wiley & Sons, Ltd.     

Enhanced Heterosexual Transmission Hypothesis for the Origin of Pandemic HIV-1

HIV-1 M originated from SIVcpz endemic in chimpanzees from southeast Cameroon or neighboring areas, and it started to spread in the early 20th century. Here we examine the factors that may have contributed to simian-to-human transmission, local transmission between humans, and export to a city. The region had intense ape hunting, social disruption, commercial sex work, STDs, and traffic to/from Kinshasa in the period 1899–1923. Injection treatments increased sharply around 1930; however, their frequency among local patients was far lower than among modern groups experiencing parenteral HIV-1 outbreaks. Recent molecular datings of HIV-1 M fit better the period of maximal resource exploitation and trade links than the period of high injection intensity. We conclude that although local parenteral outbreaks might have occurred, these are unlikely to have caused massive transmission. World War I led to additional, and hitherto unrecognized, risks of HIV-1 emergence. We propose an Enhanced Heterosexual Transmission Hypothesis for the origin of HIV-1 M, featuring at the time and place of its origin a coincidence of favorable co-factors (ape hunting, social disruption, STDs, and mobility) for both cross-species transmission and heterosexual spread. Our hypothesis does not exclude a role for parenteral transmission in the initial viral adaptation.     

Scalene Muscle Injections for Neurogenic Thoracic Outlet Syndrome: Case Series

Abstract: Scalene muscle injections are used to confirm the diagnosis of neurogenic thoracic outlet syndrome and predict the response of patients to surgery. We performed a retrospective study to determine if relief of pain was related to brachial plexus blockade in these patients. Methods: We reviewed the charts of 12 patients who had anterior and middle scalene muscle injections, for neurogenic thoracic outlet syndrome, between April 2009 and September 2010. The injections were performed under ultrasound guidance wherein 2 to 5 mL of 0.25% bupivacaine was injected into the belly of the anterior and scalene muscles. The following were noted: (1) sites of preprocedure pain; (2) volume injected into each of the anterior and middle scalene muscles; (3) presence of numbness after injection; and (4) presence and duration of pain relief. Results: All 12 patients had relief of their pain. Six of the twelve patients developed numbness, which ranged from blockade of the C4‐5, C6‐7, and C4‐T1 dermatomes. In the patients who developed numbness, there was no relationship between the duration of numbness and the duration of pain relief or the location of numbness and the location of pain relief. Conclusions: The relief from scalene muscle injections in patients with neurogenic thoracic outlet syndrome is not related to blockade of the brachial plexus. ?