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。

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：

BACKGROUND & AIMS: :Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

背景与目标： : 通过免疫组织化学构建组织微阵列 (tma) 以有效表征乳房中大量非侵入性上皮病变是一种吸引人的研究方法，但存在技术挑战。我们报告了方法学研究，以优化从大型乳腺癌病例对照研究中收集的非侵入性乳腺组织中构建TMAs的方法。使用具有2.0毫米直径针头的手动排列技术，我们从32名乳腺癌妇女获得的标本中构建了TMAs，这些标本包含以下目标 :( 1) 28个末端导管小叶单位 (TDLUs); (2) 28个原位导管癌和 (3) 23个浸润性癌。通过仔细的靶标选择，我们通过TMAs的第30节获得了约80% 的非侵入性靶标的持续保存。TDLU靶标的免疫组织化学染色显示肾小管30.8% 中的雌激素受体 (ER) 和50.0% 中的孕激素受体 (PR) 呈阳性染色。为了建立一种有效的方法来评估TDLUs中的染色结果，我们创建了一个分类评分系统来近似包含阳性染色细胞 (<10%，10% 至50%，> 或 = 50%) 的小管的百分比，并将结果与通过小管计数获得的结果进行比较。两种方法之间的比较表明，ER的70.8% 和PR染色的79.2% 完全一致，没有两类差异。来自单个块的相同组织类型 (TDLU或DCIS) 的多个 (最多4个) 非侵入性靶标中的ER/PR表达水平显示出良好的相关性。这些数据表明，尽管仔细选择了靶标，但产生非侵入性乳房结构的tma是可行的，并且此类核心的免疫染色可能允许对瘤周组织进行有效的免疫组织化学表征。需要对这种方法进行进一步的探索。

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。

BACKGROUND & AIMS: :Extensive literatures have shown significant trend of progressive electrical changes according to the proliferative characteristics of breast epithelial cells. Physiologists also further postulated that malignant transformation resulted from sustained depolarization and a failure of the cell to repolarize after cell division, making the area where cancer develops relatively depolarized when compared to their non-dividing or resting counterparts. In this paper, we present a new approach, the Biofield Diagnostic System (BDS), which might have the potential to augment the process of diagnosing breast cancer. This technique was based on the efficacy of analysing skin surface electrical potentials for the differential diagnosis of breast abnormalities. We developed a female breast model, which was close to the actual, by considering the breast as a hemisphere in supine condition with various layers of unequal thickness. Isotropic homogeneous conductivity was assigned to each of these compartments and the volume conductor problem was solved using finite element method to determine the potential distribution developed due to a dipole source. Furthermore, four important parameters were identified and analysis of variance (ANOVA, Yates' method) was performed using design (n = number of parameters, 4). The effect and importance of these parameters were analysed. The Taguchi method was further used to optimise the parameters in order to ensure that the signal from the tumour is maximum as compared to the noise from other factors. The Taguchi method used proved that probes' source strength, tumour size and location of tumours have great effect on the surface potential field. For best results on the breast surface, while having the biggest possible tumour size, low amplitudes of current should be applied nearest to the breast surface.

背景与目标： : 根据乳腺上皮细胞的增殖特性，大量文献显示出明显的进行性电变化趋势。生理学家还进一步推测，恶性转化是由持续的去极化和细胞分裂后细胞无法重新极化引起的，与未分裂或静息的对应物相比，癌症发展的区域相对去极化。在本文中，我们提出了一种新方法，即生物场诊断系统 (BDS)，该方法可能具有增强乳腺癌诊断过程的潜力。该技术基于分析皮肤表面电势以鉴别诊断疾病乳房异常的功效。我们通过将乳房视为仰卧状态下的半球，具有不同厚度的各层，从而开发了一种接近实际的女性乳房模型。将各向同性均匀电导率分配给每个隔室，并使用有限元方法解决体积导体问题，以确定由于偶极源而产生的电势分布。此外，确定了四个重要参数，并使用设计 (n = 参数数，4) 进行了方差分析 (ANOVA，yates方法)。分析了这些参数的影响和重要性。Taguchi方法进一步用于优化参数，以确保与来自其他因素的噪声相比，来自肿瘤的信号最大。使用Taguchi方法证明，探针的来源强度，肿瘤大小和肿瘤位置对表面电势场有很大影响。为了在乳房表面获得最佳效果，同时具有最大可能的肿瘤大小，应在最接近乳房表面的位置施加低振幅的电流。

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。

BACKGROUND & AIMS: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in 30% of female breast tumours using immunofluorometry. Our aim was to localize PSA immunohistochemically in a selected group of 27 paraffin-embedded breast tissues. A scoring system was developed for the histological assessment of PSA positivity within the breast tissue. One pathologist (DH) scored, classified and graded all tumours. Site-specific PSA staining was noted in the histology slides. Intense staining was identified in apocrine metaplasia and within the lining ductal epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing adenosis was also frequently positive for PSA staining. Hyperplastic ductal epithelium (especially of mild degree) occasionally stained positive, as did normal breast ducts. Better differentiated tumours showed PSA staining [e.g. mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining for PSA, adjacent intraductal carcinoma was also noted to stain positively, if present.

背景与目标： 前列腺特异性抗原 (PSA) 是一种最初认为仅由前列腺的上皮细胞产生的糖蛋白，最近已在使用免疫荧光法的女性乳腺肿瘤30% 中发现。我们的目标是通过免疫组织化学方法将PSA定位在27个石蜡包埋的乳腺组织的选定组中。开发了一种评分系统，用于对乳腺组织内的PSA阳性进行组织学评估。一位病理学家 (DH) 对所有肿瘤进行评分，分类和分级。在组织学载玻片中发现了位点特异性PSA染色。在顶汗腺化生和膀胱扩张的导管上皮内发现了强烈的染色。硬化性腺病病变中的上皮也经常出现PSA染色阳性。增生的导管上皮 (尤其是轻度) 偶尔呈阳性，正常的乳腺导管也是如此。分化更好的肿瘤显示PSA染色 [例如粘液癌 (胶体)]。如果浸润性导管癌显示PSA染色，则邻近的导管内癌 (如果存在) 也被阳性染色。

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。

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。

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。

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。

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：

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。

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。

BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.

背景与目标： : 我们已经在小鼠6号染色体上构建了一个> 2-Mb区域的物理图，其中包含自然杀伤基因复合物 (NKC)。该图谱包含14个重叠的酵母人工染色体的重叠群，我们在其上定位了25个NKC标记。NKC基因连接的基因编码> 17种直接控制先天NK细胞介导的肿瘤溶解和抗病的蛋白质。在本文中，我们显示Nkrp1基因聚集在A2m和Cd69基因两侧的区域中，并且大多数Ly49基因聚集在远端区域-1 Mb远处。重要的是，包含NKC的小鼠6号染色体和人类12p染色体的同义间隔是保守的。NKC物种保护表明，人类NKC可能包含小鼠病毒抗病基因Cmv1和rmp1的直系同源物。高分辨率NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定，这些基因产物赋予NK细胞针对病毒病原体的防御能力。