• 【复制错误阳性胃肠道癌中癌症相关基因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散布在整个基因组中。最近,已显示II型转化生长因子 β 受体 (TGF-beta RII) 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。我们检查了复制错误阳性胃肠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基因。发现了几种表现出不稳定性的多态性,但在所检查的区域中没有其他不稳定性。
  • 【胃十二指肠溃疡住院患者的组织学食管癌风险。】 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:
  • 【持续静脉和皮下吗啡治疗慢性癌症疼痛的前瞻性,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: 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量,疗效和副作用。符合条件的患者被转诊到姑息治疗计划,并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后,每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化,在之前的24小时内有四个或更少的抢救剂量,并且疼痛等级为无或轻度。如果连续96个小时保持这些标准,CIVI被认为等于CSCI。进入了57名患者,其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段,越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。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天的平均抢救剂量为每24小时0.83次,而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83,0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米,第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7,2.0 (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针插入点局部毒性 (轻度红斑) 的报告,需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量,都有足够的疼痛控制,并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明,静脉注射和南卡罗来纳州当作为连续输注给药时,大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。
  • 4 Cancer dormancy: from mice to man. 复制标题 收藏 收藏

    【癌症休眠: 从小鼠到人类。】 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,我们专注于对鼠b细胞淋巴瘤和人类乳腺癌中癌症休眠的研究。通过在TC攻击之前预先免疫肿瘤细胞 (TC) Ig的独特型,可以在同系小鼠中诱导终身休眠。尽管TCs的复制速度降低,但小鼠一生中仍在脾脏中维持约10(6) 个淋巴瘤细胞。复发是随机发生的。由于复制和细胞死亡之间的平衡,我们假设在复发风险非常低的情况下,乳腺癌的长期幸存者可能会出现类似的平衡。我们开发了一种针对循环肿瘤细胞 (ctc) 的灵敏检测方法,在正常年龄匹配的女性中均未发现。在乳房切除术后7-22年且没有任何疾病证据的患者中,有三分之一患有CTCs。这些ctc的半衰期可以从其他研究中推断为2-3小时。因此,TCs的复制 (可能来自微转移) 与细胞死亡之间存在精确的平衡。因此,临床治愈的乳腺癌患者的主要人群患有受自身生理机制控制的慢性疾病。我们根据实验模型和临床试验的研究推测潜在的机制。
  • 【低氧下肿瘤-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。基质细胞和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,我们调查了缺氧刺激是否会影响基质细胞以及胰腺癌细胞。我们的发现表明,缺氧显着提高了胰腺癌 (PK8) 和成纤维细胞 (MRC5) 的HIF-1alpha表达。低氧刺激加速了PK8细胞的侵袭活性,因此,当用低氧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,其侵袭能力进一步加快。缺氧条件下PK8细胞MMP-2、MMP-7、MT1-MMP和c-Met表达增加。低氧刺激还增加了MRC5细胞的肝细胞生长因子 (HGF) 分泌,导致PK8细胞中c-Met磷酸化升高。相反,通过从低氧条件培养基中去除HGF,可以降低PK8细胞的癌症侵袭,MMP活性和c-Met磷酸化水平。在免疫组织化学研究中,在周围基质以及胰腺癌细胞中观察到HIF-1alpha表达,因此表明癌症和基质细胞中都存在缺氧。此外,发现基质HGF表达不仅与癌细胞中的基质HIF-1alpha表达显着相关,而且与c-Met表达显着相关。这些结果表明,基质和癌细胞内的缺氧环境激活了HGF/c-Met系统,从而有助于胰腺癌的侵袭性特征。
  • 【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: : 尽管在抗胃癌方面取得了长足的进步,但它仍然是一种由特殊的组织学和分子特征定义的复杂致死疾病。本研究的目的是调查pRb2/p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67表达,并分析其与临床病理因素的可能相关性。通过免疫组织化学检查了47例患者的表达模式,其中27例被评估为肠型,20例被评估为弥漫型,平均随访56个月,并通过Western blot在AGS,N87,KATO-III和YCC-2中进行了检测,-3,-16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的表达增加,并且与远处转移的风险相关 (分别为P <0.05和P <0.01),表明该蛋白可能在此类癌症中具有预后价值。有趣的是,p27(KIP1) 表达水平与晚期疾病和转移风险之间存在很强的负相关 (P <0.05),而p21(WAF1) 表达水平与低度 (G1) 胃肿瘤之间存在正相关 (P <0.05),证实了这些肿瘤抑制基因在胃癌中的传统作用。最后,发现核pRb2/p130的表达水平与低级别 (G1) 胃肿瘤之间存在直接相关性,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类型及其侵袭潜力有关的致病机制。
  • 【[非洲男性乳腺癌,与瓦加杜古大学教学医院 (布基纳法索) 的5例病例有关]。】 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 (1993-1996年) 的男性乳腺癌回顾性研究。作者报告了5例代表所有乳腺癌4.16% 的病例。患者的平均年龄为61岁。诊断前症状和体征的平均持续时间为13个月。临床上所有5例均表现为晚期癌症 (根据UICC TNM系统,4个T4N2M0,1个T4N2M1),大小从5.5到11.5厘米。组织学发现: 髓质浸润性癌2例,管内浸润性癌1例,胶体粘液性癌1例,小叶浸润性癌1例。所有患者均行乳房切除术伴腋窝清除4例。放疗,化疗和激素治疗不相关,因为在布基纳法索不可用。3例患者死亡: 手术治疗后第1、10天,另外2例分别在14和17个月后死亡。我们已经看不见1个病人了。最后一个还活着。作者发现,要获得更好的预后,必须改善医疗和技术手段,增加信息并促进早期发现。
  • 【宫颈细胞学筛查-城市周围地区的知识,态度和实践。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Bailie R,Pick W,Cooper D
    BACKGROUND & AIMS: AIM:To determine the knowledge, attitudes and practice of women living in peri-urban settlements with regard to screening for cervical cancer. METHOD:A community-based questionnaire survey of 165 women living in a defined area of Khayelitsha, a peri-urban settlement on the outskirts of Cape Town. RESULTS:Two hundred households were visited, with a response rate of 84%. Median age of respondents was 27.5 years. The majority of interviewees were married (53.3%), unemployed (61.5%), had an educational status of standard 4 or less (58.1%) and had been living in Cape Town for 4 years or more (64.3%). The median parity was 2 (range 0-11). Most interviewees were currently using contraception (52.4%). One-third (35.4%; 95% CI 28.1-42.7%) of interviewees had heard of the Pap smear. Of these women, most had obtained their information from the midwife obstetric unit (MOU), and this was the most commonly reported facility where Pap tests were known to be done. The majority of interviewees did not regard the test (or the prospect thereof) as embarrassing (88.4%), painful (89.1%) or harmful (90.9%), and indicated that they would have the test done (89.1%). The most important reason for choice of where the test should be done was proximity to place of residence (83.9%). More than one-third of interviewees reported having had a Pap test (37.2%; 95% CI 28.8-44.8%). The most common reason for not having had a test was that the interviewee had never heard of it (81.3%). Most had undergone the test at a MOU (65.6%), where it had been part of an antenatal work-up (80.3%). Fewer than half of the interviewees who had undergone a test knew the result of their test. CONCLUSION:The antenatal, obstetric and family planning services in the area have been effective, to a limited extent, in providing information and conducting screening. However, these services are missing many opportunities to fulfill this function, and knowledge and practice of cervical cytology screening in this community are poor. With the implementation of a rational policy for screening in this area there is the potential to achieve good coverage.
    背景与目标:
  • 【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,已经进行了几次对胃癌 (GCA) 进行分类的尝试。最成功且广泛使用的是lauren的分类,该分类仅通过显微镜形态学区分了两种主要的癌症病因,弥漫性 (DGCA) 和肠道 (IGCA) 亚型,它们显然是不同的临床和流行病学实体。在这里,我们根据lauren分类回顾了两种主要亚型胃癌流行病学,组织病理学和分子病理学方面的主要差异。然而,在临床实践中,临床分期 (尤其是在预测生存率方面) 仍然优于所有胃癌分类,而与癌症类型无关。IGCA肿瘤的局部前体病变或疾病的存在,即幽门螺杆菌胃炎,萎缩性胃炎 (AG),肠上皮化生 (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唯一的普遍前体疾病。这意味着AG和achlorhydria在DGCA的发展中意义不大,并不常见,但在IGCA的发展中却是重要的步骤。尽管有越来越多的数据,但对GCA分子病理学的总体看法仍然是零碎的。尚未建立符合Laurén分类的GCA亚型分子病理学的一致差异。除TP53外,没有报道在两种组织学类型的GCA中都定期发生基因突变。染色体畸变和杂合性丧失似乎是非特异性的,并且在GCA的发展过程中没有遵循任何一致的途径。微卫星不稳定性在IGCA中比在DGCA中更常见。目前的表观遗传数据表明,基因表达的大部分减少 (或丧失) 可以通过启动子高甲基化来解释,启动子高甲基化在IGCA中更常见。在DGCA中,特定基因 (例如CDH1) 通常被高甲基化。与GCA相比,在恶变前病变中,基因突变和染色体畸变很少。表观遗传失调也可能代表胃癌发生前恶性阶段基因表达改变的主要机制。
  • 【P53基因的等位基因丢失与膀胱癌的肿瘤分级,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:
  • 【局限性前列腺癌的自然病程。对已发表论文进行回顾的个人观点。】 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: : 经过10年的随访,未经治疗的局部前列腺癌的病程尚不清楚。由于通常只为预期寿命超过10年的患者提供治愈性治疗,因此,如果不及时治疗,该疾病的预期病程是最大的利益。本文旨在描述无治疗意图治疗后存活10年以上的患者的结果。结果表明,局部前列腺癌患者的癌症特异性死亡率随着时间的推移而稳定增加,并且在15年后约为50%。这比报道的根治性前列腺切除术系列要高得多。即使许多死亡发生在老年,前列腺癌的死亡也被证明与显着的发病率,姑息治疗的需求,医院护理和费用有关。因此,预防前列腺癌死亡不仅是挽救生命的问题,而且还可以防止疾病造成的痛苦。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到临床上重要的癌症。如果诊断程序仅限于预期寿命长的患者,则过度诊断似乎并不常见。局限性前列腺癌是一种生长缓慢但进行性的肿瘤性疾病。当被诊断为预期寿命较长的男性时,应该这样处理。
  • 【克隆一种在癌症中高表达的基因,该基因编码一种新型含KH结构域的蛋白质。】 复制标题 收藏 收藏
    DOI:10.1038/sj.onc.1201110 复制DOI
    作者列表:Müeller-Pillasch F,Lacher U,Wallrapp C,Micha A,Zimmerhackl F,Hameister H,Varga G,Friess H,Büchler M,Beger HG,Vila MR,Adler G,Gress TM
    BACKGROUND & AIMS: :In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.
    背景与目标: : 在先前对胰腺癌中差异表达基因的大规模筛选中,我们鉴定了一个在癌症中高度过表达的基因,该基因编码具有四个K同源 (KH) 域的新型蛋白质。KH结构域存在于RNA结合蛋白的子集中,包括前mRNA结合 (hnRNP) K蛋白和脆弱的X智力低下基因产物 (FMR1)。通过荧光原位杂交 (FISH),将鉴定出的名为koc (含KH结构域的蛋白质在癌症中过表达) 的基因分配到7p11.5号染色体上。两个假基因位于6号和11号染色体上。克隆的koc cDNA具有250 bp 5 '-UTR、1740 bp ORF和2168 bp 3'-UTR。科威特石油公司富含非盟的3 '-非翻译区包含八个AUUUA和四个auuuuuua重申的图案。推导的具有580个氨基酸的koc蛋白具有约65,000 (65 K) 的相对分子质量 (Mr)。与正常胰腺和慢性胰腺炎组织相比,koc转录本在胰腺癌细胞系和胰腺癌组织中高度过表达。在其他人类肿瘤的组织样本中也发现了高水平的表达。由于KH结构域已被证明参与RNA合成和代谢的调节,因此我们推测koc可能通过干扰转录和或转录后过程而在肿瘤细胞增殖的调节中发挥作用。然而,koc在人类肿瘤细胞中的确切作用尚不清楚,尚待阐明。
  • 【癌症医院成人医疗重症监护室感染流行病学。】 复制标题 收藏 收藏
    DOI:10.1007/s005200050066 复制DOI
    作者列表:Berghmans T,Crokaert F,Markiewicz E,Sculier JP
    BACKGROUND & AIMS: :A prospective collection of positive antimicrobial cultures was performed over 12 consecutive months in the medical intensive care unit of a cancer hospital. In all, 144 infections and 163 pathogens were documented during 87 of the 528 admissions. Lung, urinary, ENT (ear, nose and throat) infections and bacteraemia were the most frequently documented. Staphylococcus species, Streptococcus species, Escherichia coli, Klebsiella species and Pseudomonas species were the most common pathogens. Gram-positive strains were observed predominantly during monomicrobial bacteraemia (48.9%). Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were found in 58% and 92% of the isolated strains respectively. No particular outbreak was identified. A further prospective study will be necessary to evaluate the impact of the antibiotic use on the selection of resistant strains in our ICU.
    背景与目标: : 在癌症医院的医疗重症监护病房中连续12个月进行了阳性抗菌培养的前瞻性收集。在528的87例入院期间,共记录了144例感染和163例病原体。肺,泌尿,耳鼻喉科 (耳,鼻和喉) 感染和菌血症是最常见的记录。最常见的病原体是葡萄球菌,链球菌,大肠杆菌,克雷伯菌和假单胞菌。革兰氏阳性菌株主要在单株菌血症期间观察到 (48.9%)。分离株的58% 和92% 中分别发现了耐甲氧西林金黄色葡萄球菌 (MRSA) 和表皮葡萄球菌 (MRSE)。没有发现特别的爆发。需要进行进一步的前瞻性研究,以评估抗生素使用对我们ICU中耐药菌株选择的影响。
  • 【Nm23在淋巴结阳性和淋巴结阴性子宫内膜癌中的表达。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijgo.2006.03.028 复制DOI
    作者列表:Yalçinkaya U,Ozuysal S,Bilgin T,Ercan I,Saraydaroglu O,Demir D
    BACKGROUND & AIMS: OBJECTIVE:To examine the relationships between the expression of protein Nm23 and surgical stage, histologic grade, histopathologic findings, and survival in women with endometrial carcinoma. METHODS:19 patients with lymph node involvement were matched with 24 patients without lymph node involvement and the best paraffin-embedded blocks were selected for Nm23 immunohistochemical staining. The slides were evaluated semiquantitatively according to their degree of cytoplasmic staining. Statistical analysis was performed to determine whether there was a relationship between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, lymph node metastasis, and/or lymphovascular space involvement. Survival analysis was also performed. RESULTS:Slides from 15 patients (79%) with lymph node involvement and 22 patients (88%) without lymph node involvement were found to be positive for Nm23 (P=0.01). No significant relations were observed between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, or lymphovascular space involvement. Nm23 expression was found to be significantly related to lower rates of lymph node metastasis and longer survival (P=0.02). CONCLUSION:Elevated Nm23 expression is related to lower rates of lymph node metastasis and longer survival.
    背景与目标:
  • 【辐射诱导的旁观者和其他非靶向效应: 癌症治疗的新干预要点?】 复制标题 收藏 收藏
    DOI:10.2174/156800906777723976 复制DOI
    作者列表:Mothersill C,Seymour C
    BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.
    背景与目标: : 寻找新的癌症药物靶标的一个主要问题是,这些药物通常对正常组织有毒,需要高剂量才能杀死肿瘤细胞。因此,似乎涉及对癌症治疗的低剂量反应的细胞靶标是特别令人感兴趣的,因为它们可以选择性地靶向不被治疗靶向的正常组织,并且因此可能导致令人不快的副作用或可能易于利用以提高治疗比率。作为本综述主题的一个这样的目标是辐射诱导的旁观者效应 [RIBE],该效应导致在未辐照的细胞中观察到类似辐射的反应。RIBE是一种新现象,表明在低剂量下,细胞信号传导比直接DNA损伤更重要。从历史上看,DNA一直被认为是放射治疗的目标。越来越多的意识到信号很重要,这开辟了一些重要的治疗策略,这些策略将在本文中进行讨论。RIBE似乎是组织或细胞中普遍应激反应的结果,该应激反应在组织,器官或生物体的水平而不是单个细胞的水平上表达。信号可能由所有暴露的细胞产生,但是响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET (x射线或伽马射线) 辐射暴露的主要反应是死亡反应。这具有许多凋亡特征,但可以在没有p53表达的细胞系中检测到,尽管在许多肿瘤细胞系中死亡反应受到抑制。虽然肿瘤周围未照射的正常细胞的死亡反应似乎是不利的,但实际上它可以起到保护作用并从人群中清除受损的细胞。如果正确使用,它可能会导致新药的开发,其目的不是组织破坏,而是使稳态机制能够控制肿瘤的扩张。在这种情况下,有害或有益反应的水平将与细胞群体携带的背景损害以及确定对损害反应的遗传程序有关。在尝试预测涉及辐射和其他细胞毒性药物的混合疗法的后果时,此重点可能很重要。在这篇综述中,我们对电离辐射诱导旁观者效应的潜在机制的当前知识进行了综述,并讨论了如何利用旁观者效应来生产旨在稳定组织稳态而不是组织破坏的新一代抗癌药物的问题。

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