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71.
直肠癌K—ras基因突变和细胞动力学异常 总被引:2,自引:0,他引:2
采用扩增片段限制性长度多态性分析(Amp-RFLP)和流式细胞分析技术(FCM)对直肠癌切除标本、癌旁远端肉眼观察“正常”的肠组织及正常肠粘膜,结合病理资料,比较其细胞DNA倍体性、S期百分比和增殖指数,检测K-ras基因12位密码子点突变,结果表明:直肠癌是进展迅速的恶性肿瘤,细胞增殖活性异常升高;K-ras基因突变是伴随直肠癌的一种基因异常表现,癌旁组织出现基因水平的异常发生在组织形态学和细胞动力学改变之前,是癌变发生的早期行为。 相似文献
72.
Jianguo Ma Marc Maliepaard Herman J. Kolker Jaap Verweij Jan H. M. Schellens 《Cancer chemotherapy and pharmacology》1997,41(3):186-192
The parental IGROV-1 human ovarian adenocarcinoma cell line was intermittently exposed to increasing concentrations of cisplatin
to obtain resistant sublines. A stable resistant subline with a resistance factor of 8.4 had been developed after 9 months
and 28 passages, which was denoted IGROVCDDP. A high correlation coefficient of 0.97 was found between the log cell survival and the DNA-adduct peak level during the
process of resistance development. IGROVCDDP was strongly cross-resistant to carboplatin and doxorubicin and moderately cross-resistant to etoposide, docetaxel, and topotecan.
Only minor resistance against 5-fluorouracil was observed, whereas IGROVCDDP was not cross-resistant to methotrexate. Intracellular accumulation of cisplatin was 65% lower in IGROVCDDP as compared with parental IGROV-1 at 37 °C under normal conditions. Coincubation of cisplatin with the Na+/K+-ATPase inhibitor ouabain resulted in a more pronounced decrease in platinum accumulation in IGROV-1 (44% decrease) than in
IGROVCDDP (26% decrease). Under energy-depleting conditions the accumulation of cisplatin in the parental cell line was approximately
60% lower than that observed under normal (energy [i.e., ATP] rich) culture conditions. In contrast, the accumulation in IGROVCDDP was not affected by ATP-depletion. There appeared to be no significant difference between the intracellular accumulation
of platinum in the resistant and sensitive cells under conditions of energy deprivation or when the uptake was studied at
0 °C. In conclusion, abrogation of energy-dependent accumulation in IGROVCDDP seems to be a major mechanism of resistance to cisplatin in this cell line.
Received: 21 January 1997 / Accepted: 22 July 1997 相似文献
73.
W. Bergler A. Stanek F. Riedel G. Petroianu K. Hörmann 《European archives of oto-rhino-laryngology》1998,255(8):414-419
Squamous cell carcinomas of the head and neck have been found to show a high expression of the receptor for epidermal growth
factor (EGF). This overexpression of the receptor has been associated with malignant transformation of cells, although there
is still debate as to what extent this receptor takes part in the proliferation of malignant cells and which function it fulfills.
The factors which determine receptor-ligand interaction are also not clearly defined. That the extracellular domain of the
EGF receptor carries carbohydrate or sialoglycan structures might be important for function of the receptor. Since tumor specific
enzymes can possibly alter such structures, it was the aim of our study to investigate the role of these structures on the
EGF receptor during the proliferation of head and neck carcinomas. We used the human laryngeal squamous carcinoma cell line
HLaC 79 and altered, for the first time, specific glycan structures with sialidase α-2,3 and α-2,6, causing desialylation.
Changes were also produced by endo-β-galactosidase and sialyltransferase. Findings were monitored by labeling with bromo-deoxyuridine.
To determine receptor affinity, 125I-labeled EGF was employed. Results showed that both cell proliferation and receptor affinity depended on the level of sialylation
of the receptor carbohydrate side chains. Desialylation led to a statistically significant reduction of tumor cell proliferation
to 65 ± 33% (P < 0.01), while receptor affinity decreased to 70 ± 26% (P < 0.01).The importance of EGF receptor for the proliferation of malignant cells seems to depend on the level of sialylation
of glycan structures on receptor protein. A release of enzymes by tumor cells may then produce auto-control of tumor proliferation
on its own.
Received: 5 November 1997 / Accepted: 21 April 1998 相似文献
74.
The 1.5 GHz Electromagnetic Near-field Used for Cellular Phones Does Not Promote Rat Liver Carcinogenesis in a Medium-term Liver Bioassay 总被引:3,自引:1,他引:3
Katsumi Imaida Masao Taki So-ichi Watanabe Yoshitsugu Kamimura Takayasu Ito Tsuyoshi Yamaguchi Nobuyuki Ito Tomoyuki Shirai 《Cancer science》1998,89(10):995-1002
We have recently established that local exposure to a 929.2 MHz electromagnetic near-field, used for cellular phones, does not promote rat liver carcinogenesis in a medium-term bioassay system. In the present study, a 1.439 GHz electromagnetic near-field (EMF), another microwave band employed for cellular phones in Japan, was similarly investigated. Time division multiple access (TDMA) signals for the Personal Digital Cellular (PDC) Japanese cellular telephone standard system were directed to rats through a quarter-wavelength monopole antenna. Numerical dosimetry showed that the peak SARs within the liver were 1.91–0.937 W/kg, while the whole-body average specific absorption rates (SARs) were 0.680–0.453 W/kg, when the time-averaged antenna radiation power was 0.33 W. Exposure was for 90 min a day, 5 days a week, over 6 weeks, to male F344 rats given a single dose of diethylnitrosamine (200 mg/kg, i.p.) 2 weeks previously. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At week 8, the experiment was terminated and the animals were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P)-positive foci in the livers of exposed (48) and sham-exposed rats (48). Despite increased serum levels of corticosterone, adrenocorticotropic hormone (ACTH) and melatonin, the numbers and the areas of GST-P-positive foci were not significantly altered by the exposure. These findings clearly indicated that local body exposure to a 1.439 GHz EMF, as in the case of a 929.2 MHz field, has no promoting effect on rat liver carcinogenesis in the present model. 相似文献
75.
76.
Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations
《Seminars in oncology》2016,43(4):501-513
Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell–tumor cell proximity). Evaluating such “trans-cellular pharmacology,” in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell’s biological role. We have termed this form of nearest neighbor image analysis of drug action “proximity PD microscopy,” to indicate the importance of the location of the PD-biomarker response within the cellular landscape of a tumor specimen. We discuss herein the major modes of immunotherapy, and lay out a blueprint for using PD assessment to optimize dosage regimens of single agents and guide development of combination immunotherapy regimens, using PD1/PD-L1 immune checkpoint inhibition as a case study. 相似文献
77.
Effect of Punarnavine on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of Punarnavine enhanced Natural Killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared to the metastatic tumor-bearing control. Production of cytokines such as IL-2 and IFN-γ were significantly enhanced by the administration of Punarnavine compared to the untreated metastatic tumor-bearing control. Peaks of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α were significantly lowered by Punarnavine administration compared to metastatic control. The level and expression of TIMP-1 was also enhanced by the administration of Punarnavine compared to metastatic tumor bearing control. These results indicate Punarnavine could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice. 相似文献
78.
79.
80.
Omar El-Gayar Prem Timsina Nevine Nawar Wael Eid 《International journal of medical informatics》2013,82(8):637-652
BackgroundRecent advances in information technology (IT) coupled with the increased ubiquitous nature of information technology (IT) present unique opportunities for improving diabetes self-management. The objective of this paper is to determine, in a systematic review, how IT has been used to improve self-management for adults with Type 1 and Type 2 diabetes.MethodsThe review covers articles extracted from relevant databases using search terms related information technology and diabetes self-management published after 1970 until August 2012. Additional articles were extracted using the citation map in Web of Science. Articles representing original research describing the use of IT as an enabler for self-management tasks performed by the patient are included in the final analysis.ResultsOverall, 74% of studies showed some form of added benefit, 13% articles showed no-significant value provided by IT, and 13% of articles did not clearly define the added benefit due to IT. Information technologies used included the Internet (47%), cellular phones (32%), telemedicine (12%), and decision support techniques (9%). Limitations and research gaps identified include usability, real-time feedback, integration with provider electronic medical record (EMR), as well as analytics and decision support capabilities.ConclusionThere is a distinct need for more comprehensive interventions, in which several technologies are integrated in order to be able to manage chronic conditions such as diabetes. Such IT interventions should be theoretically founded and should rely on principles of user-centered and socio-technical design in its planning, design and implementation. Moreover, the effectiveness of self-management systems should be assessed along multiple dimensions: motivation for self-management, long-term adherence, cost, adoption, satisfaction and outcomes as a final result. 相似文献