Light During Darkness and Cancer: Relationships in Circadian Photoreception and Tumor Biology

The relationship between circadian phototransduction and circadian-regulated processes is poorly understood. Melatonin, commonly a circadian phase marker, may play a direct role in a myriad of physiologic processes. The circadian rhythm for pineal melatonin secretion is regulated by the hypothalamic suprachiasmatic nucleus (SCN). Its neural source of light input is a unique subset of intrinsically photosensitive retinal ganglion cells expressing melanopsin, the primary circadian photopigment in rodents and primates. Action spectra of melatonin suppression by light have shown that light in the 446–477 nm range, distinct from the visual system’s peak sensitivity, is optimal for stimulating the human circadian system. Breast cancer is the oncological disease entity whose relationship to circadian rhythm fluctuations has perhaps been most extensively studied. Empirical data has increasingly supported the hypothesis that higher risk of breast cancer in industrialized countries is partly due to increased exposure to light at night. Studies of tumor biology implicate melatonin as a potential mediator of this effect. Yet, causality between lifestyle factors and circadian tumor biology remains elusive and likely reflects significant variability with physiologic context. Continued rigorous empirical inquiry into the physiology and clinical implications of these habitual, integrated aspects of life is highly warranted at this time.     

Effect of Grape Procyanidins on Tumor Angiogenesis in Liver Cancer Xenograft Models

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported topossess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are consideredas good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograftmodel was established using H22 cells subcutaneously injected into mice and used to assess different concentrationsof grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascularendothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry,while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD andVEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlationbetween MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possiblyby inhibiting tumour angiogenesis.     

Lung Cancer Biology

Lung cancer remains a major problem and will continue to be a major problem in oncology over the next number of decades. Treatment results have remained static over the past 10 to 20 years with modest improvements in overall survival. However, during that time, there has been an explosion in our knowledge of the biological and molecular events involved in the pathogenesis of lung cancer. A better understanding of these should allow the development of new therapeutic strategies for the intervention and treatment of patients with this disease. Moreover, the next decade will allow us to clearly evaluate the role that these biomarkers will have in the early detection of lung cancer and perhaps treatment results will be significantly improved.     

The Mouse Tumor Biology database

The laboratory mouse has long been an important tool in the study of the biology and genetics of human cancer. With the advent of genetic engineering techniques, DNA microarray analyses, tissue arrays and other large-scale, high-throughput data generating methods, the amount of data available for mouse models of cancer is growing exponentially. Tools to integrate, locate and visualize these data are crucial to aid researchers in their investigations. The Mouse Tumor Biology database (http://tumor.informatics.jax.org) seeks to address that need.     

肿瘤标志物与胃腺癌生物学行为的相关性研究

引言胃癌的发生、发展是一个多因素、多阶段、多基因变异的累积过程。人们希望寻找胃癌发生发展过程中的癌基因标记,建立简便可行的早期诊断指标和预后指标。我们检测100例胃腺癌患者组织中nm23、PCNA表达水平和其中53例患者术前、术后血清中CA72-4、CA19-9水平,探讨它们与胃癌生物学行为的关系。现将结果报告如下。1材料和方法1.1材料2003年1月~2004年9月经病理确诊的胃腺癌患者100例,其中男性80例,女性20例,年龄32~70岁,中位年龄53岁。同期门诊体检正常人40例,胃炎病人20例为对照。1.2方法1.2.1组织PCNA、nm23的测定采用SP二步法。采用单盲法2人阅片。nm23定位于细胞浆,PCNA定位于细胞核,癌细胞浆或细胞核呈棕黄色颗粒者为阳性细胞,阳性细胞超过肿瘤细胞的20%为阳性;细胞浆或细胞核呈透明或无色者为阴性细胞。1.2.2血清CA72-4、CA19-9的测定采用电化学发光法。CA72-4>3.8ng/ml、CA19-9>39u/ml为异常。2结果2.1PCNA、nm23在100例胃腺癌患者的癌组织标本中,PCNA阳性率88%;nm23阳性率23%。与临床病理特征的关系经统...     

Antiangiogenic Therapy in Brain Tumor Models

The prognosis of patients with malignant brain tumors remains poor despite new developments in neurosurgery, chemotherapy and radiotherapy. Malignant gliomas are highly vascularized, and there is ample evidence that their growth is angiogenesis-dependent. Therefore, new therapeutic approaches often include the inhibition of angiogenesis. In this review, experimental studies of antiangiogenic agents in brain tumor models are summarized. The results of these experiments as well as potential pitfalls in extrapolation to the clinic are discussed.     

New Animal Models to Probe Brain Tumor Biology,Therapy, and Immunotherapy: Advantages and Remaining Concerns

New genetic models provide better biological mimics of human tumors. The new models can give deeper insight into tumorigenesis and provide better targets for testing therapies. To use the new models most successfully, it is useful to keep in mind limitations that are harder to overcome by genetic manipulation. These include biochemical and anatomical differences between species, as well as differences in scale, both spatial and temporal. Three approaches to new genetic brain tumor models are described in the following articles. This essay provides a context, bringing out both advantages and remaining concerns. Examples are taken from work in brain tumor immunobiology and immunotherapy. The complementarity of different models, and the dichotomy between general principles and model-specific details are stressed.     

鼠脑胶质瘤模型制作方法的改良

 目的　建立简单易行、稳定的鼠C6脑胶质瘤模型。方法　SD鼠 2 0只 ,脑立体定向仪定向注射C6细胞至鼠脑尾状核 ,接种后 1、2、3、4周MRI测量肿瘤大小 ,每日观察鼠体重变化 ,处死后大体解剖和病理组织学检查。结果　MRI平扫见脑组织水肿明显 ,MRI增强可见肿瘤组织明显强化 ,中线移位 ,侧脑室受压或消失。颅内接种后星形细胞胶质瘤呈Ⅰ、Ⅱ、Ⅲ、Ⅳ级不等。结论　静脉注射套管针接种C6细胞 ,取材方便 ,简单易行 ,腹腔注射造影剂可获得较好的增强效果。     

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

Abstract The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX) on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally) 24 hours before human ovarian carcinoma (SKOV3), small cell lung carcinoma (LX-1 SCLC), and glioma (UW28, U87MG, and U251) tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0%) of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive) infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.