• 【根治性膀胱切除术可改善晚期浸润性膀胱癌的疗效。】 复制标题 收藏 收藏
    DOI:10.1007/s00345-006-0111-1 复制DOI
    作者列表:Stein JP
    BACKGROUND & AIMS: :It is clear that the optimal clinical outcomes in bladder cancer patients requiring radical cystectomy are related to standard histopathologic variables of tumor grade, stage and lymph node status. However, other less well defined variables are also critical to the successful outcomes of these patients. Patients with muscle invasive bladder cancer and treating physicians should avoid unnecessary and significant treatment delays. In addition, hospital and surgeon-volume/experience are thought to be factors that may too be important components that relate to the clinical outcomes of patients following surgery. Lastly, there is a growing body of literature to support the concept of an appropriate lymphadenectomy at the time of surgery, for both node-positive and node-negative bladder cancer patients. It is becoming more obvious that there are multiple variables involved in the clinical success and outcomes of patients with bladder cancer following radical cystectomy. As treating physicians and surgeons we must be aware of these components to ensure the best outcomes for our patients.
    背景与目标: :很明显,需要根治性膀胱切除术的膀胱癌患者的最佳临床结局与肿瘤分级,分期和淋巴结状态的标准组织病理学变量有关。但是,其他定义欠佳的变量对于这些患者的成功结局也至关重要。患有肌肉浸润性膀胱癌的患者和主治医师应避免不必要和显着的治疗延迟。另外,医院和外科医生的体格/经验被认为是可能也是与手术后患者的临床结果相关的重要组成部分的因素。最后,越来越多的文献支持针对淋巴结阳性和淋巴结阴性的膀胱癌患者在手术时进行适当的淋巴结清扫术的概念。越来越明显的是,根治性膀胱切除术后膀胱癌患者的临床成功和结局涉及多个变量。作为主治医师和外科医生,我们必须意识到这些因素,以确保为我们的患者提供最佳的治疗效果。
  • 【三七能增强5-氟尿嘧啶对人大肠癌细胞的抗癌作用。】 复制标题 收藏 收藏
    DOI:10.1007/s00280-006-0350-2 复制DOI
    作者列表:Wang CZ,Luo X,Zhang B,Song WX,Ni M,Mehendale S,Xie JT,Aung HH,He TC,Yuan CS
    BACKGROUND & AIMS: PURPOSE:Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells. METHODS:The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed. RESULTS:Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase. CONCLUSIONS:This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.
    背景与目标: 目的:三七是一种常用的中草药。尽管一些研究发现三七具有抗肿瘤作用,但尚未研究该药对结肠直肠癌细胞的作用。 5-氟尿嘧啶(5-FU)是一种治疗结肠直肠癌的化学治疗药物,它会干扰癌细胞的生长。但是,这种化合物在高剂量时具有严重的副作用。在这项研究中,我们使用HCT-116人结肠直肠癌细胞系,研究了三七花提取物(NGF)和5-FU对结肠癌细胞可能的协同抗癌作用。
    方法:通过MTS细胞增殖试验评估了这些治疗方式的抗增殖活性。通过使用Hoechst 33258染色和膜联蛋白-V / PI染色分析来分析细胞凋亡作用。还分析了NGF中的四种主要单一化合物,人参皂甙Rb1,Rb3,Rc和Rg3的抗增殖作用。
    结果:5-FU和NGF均抑制HCT-116细胞的增殖。随着5-FU剂量的增加,抗增殖作用缓慢增加。与分别使用两种药物(5-FU 5 microM,31.1 /-0.4%)相比,5-FU 5 microM和NGF 0.25 mg / ml的联合使用显着提高了抗增殖效果(59.4 /-3.3%); NGF 0.25 mg / ml,25.3±3.6%)。凋亡分析表明,在此浓度下,5-FU不会发挥凋亡作用,而观察到NGF诱导的凋亡细胞,这表明NGF的抗增殖靶标可能与5-FU有所不同。已知抑制胸苷酸合酶。
    结论:这项研究表明NGF可以增强5-FU对HCT-116人结肠直肠癌细胞的抗增殖作用,并可以减少治疗结肠直肠癌所需的5-FU剂量。
  • 【紫杉醇在患有晚期胃癌的血液透析患者中​​的药代动力学:一例报告。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i32.5237 复制DOI
    作者列表:Kawate S,Takeyoshi I,Morishita Y
    BACKGROUND & AIMS: :We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 microg/L. The area under the curve of paclitaxel was 4398.6 microg x h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 micromol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.
    背景与目标: :我们首次报告了接受血液透析的晚期,不可切除胃癌患者每周紫杉醇化疗的可能性。一名因双侧多囊肾而导致慢性肾功能衰竭的50岁男子于5周内每周进行了3次血液透析,并于2004年12月发生了呕血。根据诊断为具有淋巴结转移的胃癌,我们进行了手术。执行。术后第15天,使用紫杉醇对患者进行化疗。紫杉醇以60 mg / m2的剂量在250 mL盐水中静脉滴注1 h。紫杉醇输注完成后1 h开始进行血液透析,并进行3 h。紫杉醇在第28天的第1、8和15天每周给药一次。紫杉醇的最大血浆浓度为1390 microg / L。紫杉醇曲线下的面积为4398.6微克×h / L。在第一个周期中遇到了2级白细胞减少症。输注后6至24小时内紫杉醇的血浆浓度在我们的患者中为0.01至0.1 micromol / L,并且这些浓度已被证明可有效抑制胃癌细胞的生长而不会对患者产生不良副作用。紫杉醇的血浆浓度不受血液透析的影响。我们得出的结论是,紫杉醇在肾衰竭患者中的​​药代动力学没有改变,并且每周紫杉醇是晚期胃癌血液透析患者的合适治疗方案。
  • 【接受放射治疗的鼻咽癌患者的口腔护理。】 复制标题 收藏 收藏
    DOI:10.1016/s0964-1955(96)00053-x 复制DOI
    作者列表:Shieh SH,Wang ST,Tsai ST,Tseng CC
    BACKGROUND & AIMS: A randomised trial was undertaken to compare the effect of three oral care protocols in delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy, 30 eligible patients with a mean age of 56.2 years were recruited and evenly allocated to one of the three groups using a randomly permuted blocks method. Patients allocated to group E1 and group E2 were given the same instructions on oral care at 1 day, and 1 week before radiotherapy, respectively, while those allocated to the control group were given no instructions. We use the Oral Assessment Guide to assess the oral physical conditions of these patients daily. Our findings revealed that the patients in the E2 group not only had later onset of stomatitis than those in the control and the E1 groups, but also had lesser degree of oral injury measured by the overall assessment score. We thereby recommend the use of the E2 protocol for delaying the onset of stomatitis and reducing oral injury in nasopharyngeal cancer patients undergoing radiotherapy.

    背景与目标: 进行一项随机试验以比较三种口腔护理方案在接受放射治疗的鼻咽癌患者中延迟口腔炎和减少口腔损伤的效果,招募了30名平均年龄为56.2岁的合格患者,并平均分配给其中一名患者。三组使用随机排列的块方法。分配给E1组和E2组的患者分别在放疗前1天和1周接受相同的口腔护理指导,而分配给对照组的患者则没有给予指导。我们使用《口腔评估指南》每天评估这些患者的口腔身体状况。我们的研究结果表明,E2组患者不仅比对照组和E1组患者发生口腔炎的时间要晚,而且通过总体评估得分来衡量其口腔损伤的程度也较小。因此,我们建议在接受放射治疗的鼻咽癌患者中使用E2方案延迟口腔炎的发作并减少口腔损伤。

  • 【幽门螺杆菌和胃癌:转移了全球负担。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i34.5458 复制DOI
    作者列表:Prinz C,Schwendy S,Voland P
    BACKGROUND & AIMS: :Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people (< 10%); and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA+ strains and in persons harboring genetic polymorphism of the IL-1B promoter (-511T/T) and the corresponding IL-1 receptor antagonist (IL-1RN*2). Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA+ strains and IL-1 genetic polymorphisms should be identified and treated.
    背景与目标: 幽门螺杆菌感染导致胃粘膜持续性慢性炎症,从而增加了远端胃腺癌的风险。大量研究已确定幽门螺杆菌感染与胃癌风险之间存在明显的相关性。但是,不建议普遍根除,因为在世界不同地区,癌症的预防和治疗时间仍然存在争议。西方国家的患病率正在下降,尤其是在年轻人中(<10%);并且已经观察到远端胃腺癌的下降。西方国家的风险人群仍然显示出罹患癌症的高得多的风险,尤其是在感染cagA株的患者以及具有IL-1B启动子(-511T / T)和相应的IL-1受体拮抗剂(IL- 1RN * 2)。因此,不建议在西方国家全面消灭所有感染者,并且仅限于风险人群,以实现降低风险的目的。相反,东亚国家的感染率和癌症患病率仍然很高。治疗感染者的预防策略可以在很大程度上避免胃癌的发展,并且具有巨大的临床意义。但是,在中国和日本的研究表明,胃癌的预防仅对那些没有表现出严重的组织学改变(例如萎缩和肠化生)的患者有效。因此,在中国这样的高风险人群中,预防胃癌的预防策略应特别针对年龄较小的人群,因为这些年龄段的细菌感染引起的组织学改变仍然是可逆的。在胃癌患病率较低的国家,应识别和治疗携带cagA毒株和IL-1遗传多态性的危险人群。
  • 【在复制错误阳性胃肠道癌症中,针对癌症相关基因中重复序列不稳定的明显保护。】 复制标题 收藏 收藏
    DOI:10.1038/sj.onc.1201094 复制DOI
    作者列表:Simms LA,Zou TT,Young J,Shi YQ,Lei J,Appel R,Rhyu MG,Sugimura H,Chenevix-Trench G,Souza RF,Meltzer SJ,Leggett BA
    BACKGROUND & AIMS: Genomic instability at simple repeated sequences has been observed in various types of human cancers and is considered an important mechanism in tumorigenesis. Alterations at microsatellite loci have been reported scattered throughout the genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to have inactivating mutations within coding microsatellite sequences. The demonstration of mutations in two growth regulatory genes supports the idea that other regulatory genes with repeat sequences may also be targets in tumours with defective mismatch repair. We examined genes involved in tumour suppression, cell adhesion and cell cycle regulation for mutations at small repeat sequences in replication error positive gastrointestinal cancers. Several polymorphisms were found which exhibited instability, but no other instability was present in the regions examined.

    背景与目标: 在各种类型的人类癌症中已经观察到简单重复序列的基因组不稳定性,并且被认为是肿瘤发生的重要机制。据报道,微卫星基因座的改变分散在整个基因组中。最近,研究表明转化生长因子β受体II型(TGF-βRII)和胰岛素样生长因子II受体(IGF-IIR)基因在编码微卫星序列中具有失活突变。两个生长调节基因突变的证明支持了这样的想法,即具有重复序列的其他调节基因也可能是错配修复缺陷的肿瘤的靶标。我们检查了涉及复制抑制阳性胃肠道癌中小重复序列突变的肿瘤抑制,细胞粘附和细胞周期调控的基因。发现了几个表现出不稳定性的多态性,但在检查的区域中没有其他不稳定性。

  • 【在胃十二指肠溃疡住院的患者中,通过组织学检查发现食道癌的风险。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2007-04-01
    来源期刊:Gut
    DOI:10.1136/gut.2006.109082 复制DOI
    作者列表:Bahmanyar S,Zendehdel K,Nyrén O,Ye W
    BACKGROUND & AIMS: OBJECTIVE:The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed. DESIGN AND PATIENTS:Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period. RESULTS:Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3). CONCLUSION:The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.
    背景与目标: 目的:幽门螺杆菌血清阳性与食管腺癌(OAC)风险之间的流行病学证据呈负相关。严重的胃炎胃炎不太可能在因果关系中。假设风险均一,探讨了OAC与十二指肠溃疡和胃溃疡的相关性,两者均与幽门螺杆菌感染有关,但细菌定植和胃内酸度不同。食管鳞状细胞癌(OSCC)与这些溃疡类型的可能关联也得到了解决。
    设计和患者:自1965年以来在瑞典住院患者登记表中记录的分别有61,548和81,379例未手术的十二指肠溃疡和胃溃疡患者的回顾性队列,从首次住院治疗直至癌症,死亡,移民,定型手术,或2003年12月31日。与年龄,性别和日历时期相匹配的瑞典人口相比,具有95%CI的标准发生率(SIR)表示食道癌的相对风险。
    结果:与预期相反,十二指肠溃疡患者发生OAC的风险显着增加70%(SIR 1.7,95%CI 1.1至2.5)。胃溃疡与OAC无关(SIR 1.1,95%CI 0.6至1.7)。尽管十二指肠溃疡与OSCC的少量过量无显着相关性(SIR 1.3,95%CI 0.96至1.8),但胃溃疡与80%的风险增加相关(SIR 1.8,95%CI 1.4至2.3)。
    结论:幽门螺杆菌与OAC之间的负相关并不适用于所有感染。胃定植的模式和/或对酸度的影响可能很重要。由于保留了混淆的可能性,本研究还为胃内环境在OSCC病因中的重要性提供了一些支持。
  • 【连续静脉和皮下注射吗啡治疗慢性癌症疼痛的前瞻性,在患者内交叉研究。】 复制标题 收藏 收藏
    DOI:10.1016/s0885-3924(96)00329-6 复制DOI
    作者列表:Nelson KA,Glare PA,Walsh D,Groh ES
    BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

    背景与目标: 比较了慢性癌症疼痛患者中吗啡连续静脉输注(CIVI)与吗啡连续皮下输注(CSCI)的剂量,疗效和副作用。符合条件的患者被转到姑息治疗计划,并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50%。吗啡通过McGaw / AccuPro容量输注泵静脉内(i.v.)和皮下(s.c.)输注。获得包括副作用和疼痛评估在内的基线数据后,每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内(i.v.)阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化,在过去24小时内有四个或更少的急救剂量,疼痛等级为无或轻度。如果连续96个小时保持这些标准,则认为CIVI等于CSCI。入组患者57例,其中40例可评估(女性15例,男性25例)。中位年龄为67岁(范围为30-83岁)。在整个静脉内维持稳定剂量后,所有40位参与者阶段,跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内,有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量(第2天)为5.05 mg / hr,平均稳定s.c.剂量(第4天)为5.7 mg / hr(P = 0.01)。第2天的平均急救剂量为每24小时0.83,而第4天为每24小时0.80(P = 0.6)。第2天的平均类别疼痛评分为0.83,第4天的平均疼痛评分为0.85(P = 0.7)。第2天的平均视觉模拟量表(VAS)为22.9毫米,而第4天为17.6毫米(P = 0.1)。第2天的副作用的平均发生率为1.7,而第4天的平均发生率为2.0(P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性(轻度红斑)的报道,需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时,所有患者均具有足够的疼痛控制能力,并且在较高的s.c.下具有相似的副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时,对于大多数患者而言,这两种途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

  • 9 Cancer dormancy: from mice to man. 复制标题 收藏 收藏

    【癌症休眠:从小鼠到人。】 复制标题 收藏 收藏
    DOI:10.4161/cc.5.16.2995 复制DOI
    作者列表:Marches R,Scheuermann R,Uhr J
    BACKGROUND & AIMS: :In this review, we focused on our studies of cancer dormancy in a murine B cell lymphoma and human breast cancer. Lifelong dormancy was induced in syngeneic mice by prior immunization to the idiotype of the tumor cell (TC) Ig before TC challenge. The mice maintained approximately 10(6) lymphoma cells in their spleen throughout their lifetime despite replication of the TCs at a reduced rate. Recurrences occurred randomly. Because of the balance between replication and cell death, we hypothesized that a similar balance might occur in long-term survivors of breast cancer when the risk of recurrences is very low. We developed a sensitive assay for circulating tumor cells (CTCs) which none were found in normal age-matched women. One third of patients, 7-22 years after mastectomy and without any evidence of disease, had CTCs. The half-life of these CTCs could be deduced from other studies as probably 2-3 hours. Hence, there was a precise balance between replication of TCs (presumably from micrometastases) and cell death. Therefore, a major population of clinically cured breast cancer patients have a chronic disease controlled by their own physiological mechanisms. We speculate on underlying mechanisms based both on studies in experimental models and clinical trials.
    背景与目标: :在这篇综述中,我们集中于对小鼠B细胞淋巴瘤和人类乳腺癌的癌症休眠研究。通过在TC攻击之前先对肿瘤细胞(TC)Ig的独特型进行免疫,可以在同系小鼠中终生休眠。尽管TCs的复制率降低了,但小鼠的一生中仍在脾脏中维持着约10(6)个淋巴瘤细胞。复发随机发生。由于复制和细胞死亡之间的平衡,我们假设当复发风险非常低时,长期存活的乳腺癌患者可能会发生类似的平衡。我们开发了一种循环肿瘤细胞(CTC)的灵敏检测方法,在正常年龄的女性中均未发现。乳房切除术后7-22年且无任何疾病证据的三分之一患者患有CTC。这些CTC的半衰期可以从其他研究中推断出来,大概为2-3小时。因此,在TC的复制(可能来自微转移)和细胞死亡之间存在着精确的平衡。因此,大部分临床治愈的乳腺癌患者患有受其自身生理机制控制的慢性疾病。我们基于实验模型和临床试验研究潜在的机制。
  • 【缺氧条件下的肿瘤基质细胞相互作用通过肝细胞生长因子/ c-Met途径增加了胰腺癌细胞的侵袭性。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22178 复制DOI
    作者列表:Ide T,Kitajima Y,Miyoshi A,Ohtsuka T,Mitsuno M,Ohtaka K,Koga Y,Miyazaki K
    BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.
    背景与目标: :据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中,我们调查了低氧刺激是否影响基质和胰腺癌细胞。我们的研究结果表明,缺氧显着提高了胰腺癌(PK8)和成纤维细胞(MRC5)中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性,因此,当用由低氧MRC5细胞制备的条件培养基(低氧条件培养基)培养低氧PK8细胞时,侵袭性进一步加快。在缺氧条件下,PK8细胞中的MMP-2,MMP-7,MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子(HGF)分泌,这导致PK8细胞中c-Met磷酸化的升高。相反,通过从低氧条件培养基中除去HGF,可以降低PK8细胞的癌浸润,MMP活性和c-Met磷酸化升高。在免疫组织化学研究中,在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达,因此表明在癌细胞和基质细胞中均存在缺氧。此外,发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统,从而促进了胰腺癌的侵袭性侵袭性特征。
  • 【胃癌中pRb2 / p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67表达模式的免疫组织化学分析。】 复制标题 收藏 收藏
    DOI:10.1002/jcp.20833 复制DOI
    作者列表:Mattioli E,Vogiatzi P,Sun A,Abbadessa G,Angeloni G,D'Ugo D,Trani D,Gaughan JP,Vecchio FM,Cevenini G,Persiani R,Giordano A,Claudio PP
    BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.
    背景与目标: :尽管在对抗胃癌方面取得了长足的进步,但它仍然是由特殊的组织学和分子学特征定义的复杂致死性疾病。本研究的目的是研究pRb2 / p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67的表达,并分析它们与临床病理因素的可能关系。通过免疫组织化学检查了47例患者的表达模式,其中27例为肠型,20例为弥散型,平均随访56个月,并通过Western blot检测AGS,N87,KATO-III和YCC-2 ,-3,-16个胃细胞系。总体而言,胃癌显示EZH2与高水平的p53,Ki-67和细胞质pRb2 / p130相关(分别为P <0.05和P <0.01)。在肠型中发现EZH2表达增加,并且与远处转移的风险相关(分别为P <0.05和P <0.01),表明该蛋白可能在这种类型的癌症中具有预后价值。有趣的是,观察到p27(KIP1)表达水平与晚期疾病和转移的风险之间存在强烈的负相关(P <0.05),而p21(WAF1)和低度胃癌(G1)的表达水平之间呈正相关。肿瘤(P <0.05),证实了这些肿瘤抑制基因在胃癌中的传统接受作用。最后,在核pRb2 / p130的表达水平与低度(G1)胃肿瘤的表达水平之间发现了直接相关性,具有统计学意义(P <0.05)。总之,这些数据可能有助于进一步阐明与两种主要胃癌组织学类型及其侵袭潜能有关的致病机制。
  • 【[非洲男性乳腺癌,瓦加杜古大学教学医院(布基纳法索)的Apropos 5例)。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Sano D,Dao B,Lankoandé J,Touré B,Sakandé B,Traoré SS,Wandaogo A,Dakouré R,Sanou A
    BACKGROUND & AIMS: :A retrospective study of male breast cancer was undertaken at Ouagadougou University Teaching Hospital over a 3 year period (1993-1996). Authors report 5 cases representing 4.16% of all breast cancers. The patients' mean age was 61 years. The average duration of signs and symptoms before the diagnosis was 13 months. Clinically all the 5 cases presented advanced cancers (4 T4N2M0, 1 T4N2M1 according to UICC TNM System) with size ranging from 5.5, to 11.5 cm. Histology found: 2 medullary infiltrating carcinoma, 1 canalar infiltrating carcinoma, 1 colloid mucous carcinoma and 1 lobular infiltrating carcinoma. All patients had mastectomy associated with axillary clearance in 4 cases. Radiotherapy, chemotherapy and hormonotherapy were not associated because unavailable in Burkina Faso. Three patients died: the first, 10 days after surgical treatment and the 2 others respectively after 14 and 17 months. We have lost sight 1 patients. The last one is still alive. Authors find that to get better prognosis, it is important to improve medical and technical means, to increase information and to promote early detection.
    背景与目标: :在瓦加杜古大学教学医院进行了为期3年(1993年至1996年)的男性乳腺癌回顾性研究。作者报告了5例病例,占所有乳腺癌的4.16%。患者的平均年龄为61岁。诊断前平均体征和症状持续时间为13个月。临床上,所有5例患者均出现晚期癌(根据UICC TNM System,4例T4N2M0、1例T4N2M1),大小在5.5至11.5厘米之间。组织学发现:2个髓样浸润癌,1个管状浸润癌,1个胶体粘​​液癌和1个小叶浸润癌。所有患者均进行了伴有腋窝清除术的乳房切除术4例。放疗,化学疗法和激素疗法没有联系,因为布基纳法索无法使用。 3例患者死亡:第一例,手术治疗10天后死亡,另外2例分别在14个月和17个月后死亡。我们失去了视力1例患者。最后一个还活着。作者发现,要获得更好的预后,重要的是改善医学和技术手段,增加信息并促进早期发现。
  • 【胃癌的病理学和分子生物学。】 复制标题 收藏 收藏
    DOI:10.1016/j.bpg.2006.03.016 复制DOI
    作者列表:Vauhkonen M,Vauhkonen H,Sipponen P
    BACKGROUND & AIMS: :Several attempts to classify gastric cancer (GCA) have been made over the past decades. Most successful, and widely used, is the classification by Laurén, which distinguishes, by microscopical morphology alone, two main cancer pathogeneses, diffuse (DGCA) and intestinal (IGCA) subtypes, which appear clearly as dissimilar clinical and epidemiological entities. Here we review the main differences in epidemiology, histopathology, and molecular pathology of the two main subtypes of gastric carcinomas based on Laurén classification. In clinical practice, however, clinical staging, particularly in predicting the survival, still remains superior to all classifications of gastric cancer independent of cancer type. The existence of local precursor lesions or conditions of IGCA tumours, i.e. Helicobacter pylori gastritis, atrophic gastritis (AG), intestinal metaplasia (IM), adenoma, dysplasia, and intramucosal neoplasia, is firmly established. The links of DGCA with intestinal-type epithelium, AG or IM are poor, or do not exist. So far, H. pylori gastritis is the only universal precursor condition for DGCA. It implies that AG and achlorhydria are of minor significance and infrequent in the development of DGCA but are important steps in that of IGCA. Despite an increasing body of data, the overall view on molecular pathology of GCA remains fragmentary. No consistent differences in the molecular pathology of GCA subtypes to meet the Laurén classification have been established. With the exception of TP53, no gene mutation occurring regularly in both histological types of GCA has been reported. Chromosomal aberrations and loss of heterozygosity seem to be non-specific and do not follow any consistent route in the progression of GCA. Microsatellite instability is more commonly found in IGCA than in DGCA. The present epigenetic data suggest that most of the decrease (or loss) of gene expression may be explained by promoter hypermethylation which is more often found in IGCA. In DGCA specific genes such as CDH1 are more often hypermethylated. Compared with GCA, in premalignant condition lesions gene mutations and chromosomal aberrations are infrequent. Epigenetic dysregulation might also represent a major mechanism for altered gene expression in premalignant stages in gastric carcinogenesis.
    背景与目标: :在过去的几十年中,已经进行了多次尝试来对胃癌(GCA)进行分类。最成功且应用最广泛的是Laurén的分类法,该分类法仅通过显微镜形态就可以区分出两种主要的癌症病原体,即弥散(DGCA)和肠道(IGCA)亚型,它们明显表现为不同的临床和流行病学实体。在这里,我们基于Laurén分类,回顾了两种主要胃癌亚型的流行病学,组织病理学和分子病理学的主要差异。然而,在临床实践中,临床分期,尤其是在预测存活率方面,仍然优于胃癌的所有分类,而与癌症类型无关。牢固地确定了局部局部前体病变或IGCA肿瘤的状况,即幽门螺杆菌胃炎,萎缩性胃炎(AG),肠化生(IM),腺瘤,异型增生和粘膜内瘤变。 DGCA与肠型上皮,AG或IM的联系较差或不存在。到目前为止,幽门螺杆菌胃炎是DGCA的唯一通用先兆病状。这表明AG和胃酸缺乏症在DGCA的发展中意义不大,很少出现,但在IGCA中是重要的步骤。尽管有越来越多的数据,但关于GCA分子病理学的整体观点仍是零碎的。尚未建立符合劳伦分类的GCA亚型分子病理学方面的一致差异。除TP53外,在两种组织学类型的GCA中均没有定期发生基因突变的报道。染色体畸变和杂合性丧失似乎是非特异性的,并且在GCA的发展过程中未遵循任何一致的途径。在IGCA中比在DGCA中更常见微卫星不稳定性。目前的表观遗传学数据表明,基因表达的大多数减少(或丧失)可以通过在IGCA中更常见的启动子高甲基化来解释。在DGCA中,诸如CDH1之类的特定基因更经常被甲基化。与GCA相比,在癌变前病灶中,基因突变和染色体畸变很少见。表观遗传失调也可能代表了胃癌发生前癌变阶段基因表达改变的主要机制。
  • 【P53基因的等位基因缺失与膀胱癌的肿瘤等级,分期和恶性进展的相关性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1442-2042.1997.tb00144.x 复制DOI
    作者列表:Tsutsumi M,Sugano K,Yamaguchi K,Kakizoe T,Akaza H
    BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.
    背景与目标: 背景:我们检查了膀胱癌中P53基因的杂合性(LOH)缺失,并研究了P53基因在乳头状瘤恶性进展中的作用。另外,检查了复发性膀胱癌的克隆性。
    方法:分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定,石蜡包埋的组织中提取DNA,在P53基因的3个多态性位点处通过聚合酶链反应(PCR)进行扩增,并通过非放射性同位素单链构象多态性(Non-RI SSCP)分析。
    结果:在40个信息量样本中,在13个样本中检测到LOH,其中3个7级中有4个(57%),2个23级中有9个(39%),1个10级中没有10个(10%)。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明,3例(60%)在原发性肿瘤中显示LOH,2例在复发性肿瘤中显示LOH。 ,与LOH在19例(16%)的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个,仅在初始肿瘤中1个,在两个肿​​瘤中1个。
    结论:P53基因的改变被认为与肿瘤的分级有关,并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。
  • 【局限性前列腺癌的自然病程。以个人观点审阅已发表的论文。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hugosson J,Aus G
    BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.
    背景与目标: :十年随访后未经治疗的局限性前列腺癌的病程目前还不得而知。由于通常仅为预期寿命超过10年的患者提供治愈性治疗,因此,如果不及时治疗,预期的病程将是最重要的。本文旨在描述未经治疗而存活超过10年的患者的预后。结果表明,局部前列腺癌患者的癌症特异性死亡率随时间稳定增加,并且在15年后约为50%。这是一个比已报道的前列腺癌根治术系列高得多的数字。即使许多死亡发生在老年,前列腺癌的死亡也被证明与明显的发病率,姑息治疗的需要,医院护理和费用有关。因此,预防前列腺癌的死亡不仅是挽救生命的一年,而且是预防由该疾病引起的痛苦的问题。现代诊断工具,例如前列腺特异性抗原,似乎可以在绝大多数患者中检测出具有临床意义的癌症。如果诊断程序仅限于预期寿命较长的患者,则过度诊断似乎不常见。局限性前列腺癌是一种生长缓慢但正在进行的肿瘤性疾病。当诊断为预期寿命较长的男性时,应照此处理。

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