Association of Epidermal Growth Factor-related Peptides and Type I Receptor Tyrosine Kinase Receptors with Prognosis of Human Colorectal Carcinomas

The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers.     

Induction of tumour necrosis factor-α by single and repeated doses of the antitumour agent 5,6-dimethylxanthenone-4-acetic acid

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a low-molecular-weight biological response modifier scheduled for clinical evaluation, induced synthesis of tumour necrosis factor- (TNF-) in serum of mice, with maximal activity being observed at 2–3 h after administration. At a dose of 27.5 mg/kg, DMXAA induced similar TNF- concentrations as did flavone-8-acetic acid given at its maximum tolerated dose (MTD; 330 mg/kg), whereas 8-methylxanthenone-4-acetic acid, which has no antitumour activity, did not induce serum TNF- at its MTD (440 mg/kg). The dependence of schedule on TNF- induction was studied by giving DMXAA to mice in two doses of 27.5 mg/kg each separated by different intervals. An interval of 0 (i.e 55 mg/kg given in a single dose) produced a TNF- concentration 9-fold that produced hy a single dose of 27.5 mg/kg. This dose, although higher than the MTD of 30 mg/kg, did not affect the health of mice at the time of assay (3 h). An interval of 1 day produced very low levels of serum TNF- after the second injection. An interval of 3 days produced high levels of serum TNF- after the second injection (9-fold that detected in mice receiving 27.5 mg/kg in a single dose) but no long-term toxicity, whereas an interval of 7 days produced an intermediate response. Thus, the first dose can either potentiate or suppress the TNF- response to a second dose. Mice with advanced subcutaneous colon 38 tumours were treated either with a single dose of DMXAA (27.5 mg/kg) or with a divided dose (two doses of 27.5 mg/kg given 3 days apart). Both the cure rate and the tumour-growth delay were enhanced by the divided-dose schedule. The results are relevant to the design of clinical administration schedules of DMXAA and emphasise the importance of TNF- induction in the antitumour response.This study was supported by the Auckland Division of the Cancer Society of New Zealand and by the Health Research Council of New Zealand     

Synchronous colon primaries have the same prognosis as solitary colon cancers

PURPOSE: This study was designed to determine the prognosis of patients with synchronous colon primary tumors. METHODS: An 18-year, multi-institutional database of 4,878 colon cancer patients was reviewed, and patients with synchronous tumors were identified. Survival for each group was calculated by the Kaplan-Meier method and compared using log-rank analysis. RESULTS: There were 160 patients (3.3 percent) with 339 synchronous tumors. Eight percent of these patients had more than two tumors at the time of diagnosis. TNM staging of all synchronous tumors was 12 percent Stage 0, 41 percent Stage I, 21 percent Stage II, 16 percent Stage III, and 7 percent Stage IV. Based on highest stage lesion, 1 percent of patients were at Stage 0, 28 percent Stage I, 33 percent Stage II, 25 percent Stage III, and 11 percent Stage IV. Disease-specific five-year survival by highest stage was 87 percent for Stage O or I, 69 percent for Stage II, 50 percent for Stage III, and 14 percent for Stage IV (all differences significant by log-rank test). These highest stage survivals for patients with synchronous tumors were not significantly different from survival of patients with same stage solitary tumors in our database or from survival of patients with solitary colon cancer in national tumor databases. CONCLUSION: For patients with synchronous colon cancers, survival is the same as for patients with solitary colon tumors on a stage-for-stage basis, when highest stage synchronous tumor is considered.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

结肠腺癌与正常结肠神经节苷脂的比较研究

我们对成人结肠腺癌和同一个体的远端正常结肠,分别分离、纯化出细胞膜神经节苷脂(GLS),经GLS定量分析,结果表明:癌组织中GLS的含量较正常结肠显著增加,结肠腺癌平均每克湿重组织含GLS39.7nmol,正常结肠平均为16.5nmol。高效薄层层析图谱显示,癌组织中,在含有单唾液酸GLS区段,存在二条肿瘤“特异”的条带,位于通常的GM2和GM1条带之后,它们分别占总神经节苷脂的3.9—6.0％、3.9—7.5％;在含有二唾液酸GLS区段,发现一条异常的GLS条带,位于GDla与GDlb之间,占总GLS5.1—6.7％,而5例正常对照中,有一例存在痕量,一例占总GLS的1.4％。比较结肠腺癌和正常结肠的不同GLS的百分含量可知:癌组织中GM3、GM2增加;GD3、GDla减少,同时GDlb和含三唾液酸以上的GLS呈减少的趋势。     

黄龙汤对动物肠运动的影响

目的：探讨黄龙汤对实验动物肠运动的作用。方法：采用肠管运动在体实验法测定排便时间及频度和肠推进运动．肠管运动的离体实验法测定动物不同肠段运动情况。结果：黄龙汤能使动物排便时间增快，次数增加，便稀且不成形。能明显促进动物在体肠推进运动。能增加动物离体回肠蠕动作用，对离体十二指肠及结肠则显示明显的抑制作用．且这种作用能被Ach短暂拮抗。结论：黄龙汤对实验动物有明显的泻下作用。可能是由于黄龙汤有促进动物肠肌运动的结果。对十二指肠及结肠显示的这种抑制作用表明本方在致泻的同时，可能有解痉止痛作用。     

急性阑尾炎术前漏诊右半结肠癌14例分析

目的 探讨预防或减少急性阑尾炎术前漏诊右半结肠癌的措施及二者并存的术中处理。方法 对我院1990年1月～2002年10月收治的14例急性阑尾炎术前漏诊右半结肠癌的原因及并存机理进行回顾性分析。结果 14例漏诊患者中，5例行Ⅰ期右半结肠切除术；3例行Ⅰ期右半结肠切除、回肠造瘘术；2例行I期可疑病灶切除、回肠或盲肠造瘘术，Ⅱ期行右半结肠切除术；3例行回肠造瘘、腹腔引流术，Ⅱ期行右半结肠切除术；1例单纯行阑尾切除术，漏诊肝曲结肠癌，术后并发肠梗阻，剖腹控查行Ⅰ期右半结肠切除、回肠造瘘术。结论 掌握外科基本理论，遵循外科基本原则，避免惯性思维，减少漏诊机会，常能够避免急性阑尾炎术前漏诊右半结肠癌导致处理不当而带来的一系列问题。     

应用 PCR 方法检测大肠癌组织中的 HPV DNA

本文采用聚合酶链式反应（ＰＣＲ）的方法，对２０例大肠癌患者的手术切除标本进行了人体乳头瘤病毒（ＨＰＶ）ＤＮＡ的检测。结果发现４例（２０％）ＨＰＶ１６型扩增阳性，其中１例显示ＨＰＶ１６．１８型双重阳性。初步表明大肠癌组织中存在ＨＰＶ的感染。     

人原发性大肠癌的染色体分析

用改良的直接法分析了20例大肠癌新鲜瘤组织及4例大肠癌细胞系的细胞遗传学改变，发现瘤细胞多为异倍体，染色体众数以亚二倍体居多；核型分析发现，其杂色体数目畸变为，13号染色体增多；17号、1号和Y染色体的丢失，结构畸变最常累及1号染色体，断裂声、1q21出现率较高，其次为1p13区的断裂及末端丢失。提示1号染色体结构异常可能为原发性大肠癌特征性染色体改变之一。     

The therapeutic effect of intratumoral injection of GM-CSF gene-modified allogenic macrophages on tumor-bearing mice

Both the antigen presenting ability and the cytotoxicity of macrophages can be enhanced by GM-CSF gene transfer. In the present study, the therapeutic effect of intratumoral injection with GM-CSF gene-modified allogenic macrophages on tumor-bearing mice observed. The peritoneal macrophages of C57BL/6 mice were transfected with GM-CSF gene mediated by recombinant adenovirus and the subcutaneous CT26 colon adeno-carcinoma-bearing BALB/c mice were treated by intratumoral injection of the above macrophages. The survival time of the tumor-bearing mice were prolonged significantly and some tumor mass disappeared completely. The necroses of the tumor cells and massive infiltration of inflammatory cells were observed 6 days after treatment 30 days after treatment, only the leftover of tumor cells and the inflammatory cells remained. The data indicated that introtumoral injection of GM-CSF gene-modified allogenic macrophages displayed more potent therapeutic effect on the preestablished tumor-bearing mice. Supported by National High Biotechnology Foundation (Z20-01-03). This is one of papers of the special issue on gene therapy research (Chin J Cancer Res Vol. 9 No. 4 December, 1997).