腫瘤生物學(xué)特性

1、關(guān)于腫瘤的生物學(xué)特性第一張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月物質(zhì)代謝及酶的變化腫瘤細(xì)胞的分化腫瘤細(xì)胞的生長(zhǎng)腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制腫瘤侵襲和轉(zhuǎn)移相關(guān)基因第二張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月第三張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月核酸代謝核酸增多是腫瘤迅速生長(zhǎng)的物質(zhì)基礎(chǔ)DNA拓?fù)洚悩?gòu)酶物質(zhì)代謝及酶的變化端粒酶第四張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月DNA拓?fù)洚悩?gòu)酶存在于細(xì)胞核內(nèi)的一類酶，他們能夠催化DNA鏈的斷裂和結(jié)合，從而控制DNA的拓?fù)錉顟B(tài)。 DNA拓?fù)洚悩?gòu)酶通過(guò)形成短暫的單鏈裂解-結(jié)合循環(huán)，催化DNA復(fù)制的拓?fù)洚悩?gòu)狀態(tài)的變化 核酸代謝物質(zhì)代謝及酶的變化第五張，PP

2、T共四十七頁(yè)，創(chuàng)作于2022年6月(A) Classification of human DNA topoisomerases. Type IB are the only enzymes that form cleavage complexes (cc) with 30-phosphotyrosyl (30-P-Y) intermediates.(C) Noncovalent binding of type IB enzymes. (D) Scheme of the 30 phosphotyrosine covalent bond in the Top1cc. The arrow indica

3、tes the reversible (religation) reaction, which is favored under normal conditions. G) Scheme of the 50-phosphotyrosine covalent bond in the Top2cc. 第六張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月第七張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月It is thought that length or integrity of chromosome end is used as a mitotic counting mechanism in vitro

4、 核酸代謝物質(zhì)代謝及酶的變化端粒酶Each mammalian chromosome end has a distinctive DNA-protein structure, which prevents the degradation and fusion of chromosome ends by helping distinguish chromosome ends from a double strand break in the genomic DNA.第八張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Mammalian have a stretch of a simple repeat

5、 sequence unit (TTAGGG) and in , length is 1520 kb. Fifty to 200 bp of the telomeric DNA shortens at each round of mitosis. When average DNA reaches a critically short length, about 47 kb, is arrested Irreversibly.核酸代謝端粒酶物質(zhì)代謝及酶的變化第九張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月物質(zhì)代謝及酶的變化核酸代謝蛋白質(zhì)代謝糖代謝酶系統(tǒng)第十張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月

6、物質(zhì)代謝及酶的變化酶系統(tǒng)增殖相關(guān)和分化相關(guān)的酶轉(zhuǎn)化相關(guān)和演進(jìn)相關(guān)的酶細(xì)胞惡變的指標(biāo)。主要正常細(xì)胞發(fā)生轉(zhuǎn)化， 總可出現(xiàn)這類酶活性的改變。演進(jìn)相關(guān)的酶酶活性于惡性程度呈平行關(guān)系的酶轉(zhuǎn)化相關(guān)第十一張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞的分化各種不同類型細(xì)胞(分化細(xì)胞)同一來(lái)源的幼稚細(xì)胞?分化的概念特定的生理功能特定的生化特征特定的形態(tài)結(jié)構(gòu)第十二張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月穩(wěn)定性全能性選擇性條件可逆性細(xì)胞分化特點(diǎn):未分化惡性腫瘤是由于起源組織中的干細(xì)胞喪失了分化的能力。第十三張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞分化異常的機(jī)制遺傳學(xué)改變信號(hào)轉(zhuǎn)化異常微環(huán)境的影響誘導(dǎo)

7、分化治療腫瘤第十四張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞的生長(zhǎng)細(xì)胞增殖活性的原位檢測(cè)方法及意義細(xì)胞增殖活性：細(xì)胞增生快慢的能力DNA 含量測(cè)定確定增生細(xì)胞的比例DNA ploidy and proliferative activity as represented by the S-phase fraction (SPF).A link exists between high SPF values and increased risk of recurrence and death for patients with primary BC,Flow cytometry 法第十五張，

8、PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞的生長(zhǎng)免疫組織化學(xué)方法Several monoclonal antibodies reacting with different proliferating cell nuclear antigens have been described, such as PCNA, Ki-67 and MIB 1, KiS1 and others.The Ki-67/MIB 1 protein has a prognostic value for many types of malignant tumors.Ki-67Only papers published

9、 in English in peer reviewed journals before June 2004 that include at least 100 evaluable patients were selected. Inaddition, the prognostic and predictive role of the proliferative markers had to be assessed through multivariate analyses. One hundred and thirty-two papers fulfilled these criteria

10、and 159 516 patients analyzed.第十六張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞的生長(zhǎng)免疫組織化學(xué)方法細(xì)胞周期蛋白The different cyclins：the concentration rise and fall at specific stages throughout the cell cycle, have a temporally distinct and highly regulated pattern of expression, i.e. they are synthesized and degraded at specific sta

11、ges of the cell cycle.Cyclin E is the limiting factor for G1 phase progression and S phase entryRecently, several splice variants of cyclin E1, which are not present in normal cells, have also been discovered; which stimulate cells to progress through the cell cycle much more efficiently than the fu

12、ll length cyclin E1第十七張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Cyclin E was prognostic in seven out of 10 studies.腫瘤細(xì)胞的生長(zhǎng)免疫組織化學(xué)方法細(xì)胞周期蛋白The overexpression of cyclin E was accompanied by the appearance of low molecular weight (LMW) isoforms, and both were a reliable prognostic marker in stage IIII BC patients.High levels

13、 of cyclin E1 were predictive of resistance to tamoxifen adjuvant therapy in 108 node-positive BC patients, independently of ER status.第十八張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Cyclin D1腫瘤細(xì)胞的生長(zhǎng)細(xì)胞周期蛋白D-type cyclins are other key regulator proteins of the G1 phase progression.The protein is synthesized in response togr

14、owth factors; its levels reach a maximum in the mid-G1phase of the cell cycle and then begin to drop. It appears that the association of cyclin D1 to Cdk is crucial to drive cells to the restriction point where the cell is committed to divide第十九張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月A strong correlation between overe

15、xpression of cyclin D1 and HR-positivity has been reported in the majority of trials, but cyclin D1 does not appear to be a strong prognosticmarker. In fact, its overexpression has been associated with better RFS in only one studyCyclin D1腫瘤細(xì)胞的生長(zhǎng)細(xì)胞周期蛋白第二十張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤的生長(zhǎng)與擴(kuò)散腫瘤的擴(kuò)散方式直接蔓延轉(zhuǎn)移met

16、astasis瘤細(xì)胞從原發(fā)部位 侵入淋巴管、血管和體腔，擴(kuò)散到其它部位， 形成與原發(fā)瘤相同的腫瘤。第二十一張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月轉(zhuǎn)移metastasis腫瘤的生長(zhǎng)與擴(kuò)散腫瘤的擴(kuò)散方式淋巴道轉(zhuǎn)移Lymphatic metastasis is a predictor of poor outcome in many solid malignancies . The presence of lymph node metastases decreases the 5-year survival of melanoma patients independent of other pro

17、gnostic factors of the primary tumor.第二十二張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Figure 1. Development of lymphatic vessels in embryogenesis and cancerSome of the proteins that are important in theseevents are shown underneath each section.Arrows denote the direction of lymph flow in thelymphatic vessels.第二十三張，PPT共四十七

18、頁(yè)，創(chuàng)作于2022年6月轉(zhuǎn)移metastasis腫瘤的生長(zhǎng)與擴(kuò)散腫瘤的擴(kuò)散方式血道轉(zhuǎn)移第二十四張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月轉(zhuǎn)移metastasis腫瘤的生長(zhǎng)與擴(kuò)散腫瘤的擴(kuò)散方式種植性轉(zhuǎn)移體腔內(nèi)臟器的腫瘤蔓延至器官表面時(shí)， 瘤細(xì)胞可脫落種植于體腔和各器官表面形成多數(shù)轉(zhuǎn)移瘤。第二十五張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制腫瘤侵襲是轉(zhuǎn)移的前提；侵襲和轉(zhuǎn)移的步驟：脫離原發(fā)瘤群體向周圍組織浸潤(rùn)與局部血管或淋巴管密切接觸， 穿過(guò)其管壁穿透管壁， 在基質(zhì)中增生轉(zhuǎn)移灶的形成和生長(zhǎng)第二十六張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分

19、子侵襲和轉(zhuǎn)移的步驟：脫離原發(fā)瘤群體以配體核受體結(jié)合的形式， 使細(xì)胞間發(fā)生粘連integrin跨膜糖蛋白十六種a亞單位和8種b亞單位第二十七張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分子cadherin與細(xì)胞骨架連接人類至少有10多種鈣粘蛋白E； N； P第二十八張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分子IgSF跨膜蛋白具有與Ig類似的結(jié)構(gòu)第二十九張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分子Selectin familycancer cells adhere to by

20、a process similar to that of LC homing. In this model, cells in flow are captured on the endothelial surface.第三十張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月transient adhesive interactions by cells with endothelial selectins(rolling), and firmly anchored on (firm adhesion) to enable entry into the underlying tissue. The se

21、lectins, particularly E-selectin, are recognized to mediate adhesion and thus potentiate of certain cancers腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分子Selectin family第三十一張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制細(xì)胞黏附與細(xì)胞黏附分子CD44A transmembrane protein Essential for the homing and properties of leukemicCells, CD44 has also been foun

22、d to support anchorage-independent growth in vitro and tumor growth and in experimental models of solid cancers 第三十二張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞擴(kuò)散的過(guò)程機(jī)制腫瘤細(xì)胞從原發(fā)灶分離的機(jī)制腫瘤細(xì)胞表面黏附分子減少。癌細(xì)胞鈣含量降低惡性腫瘤細(xì)胞間連接結(jié)構(gòu)數(shù)量減少腫瘤細(xì)胞表面電荷增加第三十三張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞向周圍組織的浸潤(rùn)細(xì)胞外基質(zhì)的降解瘤細(xì)胞的運(yùn)動(dòng)趨化因子的作用腫瘤血管生成第三十四張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤血管

23、生成腫瘤細(xì)胞向周圍組織的浸潤(rùn)第三十五張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤血管生成腫瘤組織中微血管的來(lái)源瘤細(xì)胞生成的多種生長(zhǎng)因子誘導(dǎo)瘤體生成微血管殘存于流體的宿主血管逐漸變?yōu)槟[瘤血管VEGF是迄今鑒定出來(lái)的最重要的血管生成因子第三十六張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Fig. 1 Switching on the angiogenic phenotype in tumors by genetic and epigenetic factors. Both malignant and nonmalignant cells produce multiple angiogenic fa

24、ctors and cytokines to induce tumor neovascularization. Endogenous angiogenesis inhibitors are down regulated to support the angiogenic phenotype第三十七張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤細(xì)胞侵入血管和淋巴管侵入血管和淋巴管在循環(huán)中運(yùn)行到達(dá)遠(yuǎn)處部位Fig. 1.Schematic diagram showing how production of VEGF-C and VEGF-C in tumors can induce lymphang

25、iogenesis, leading to increased lymphatic vessel density in the vicinity of the tumor, and subsequently to metastasis of invasive tumor cells via the lymph vessels. Fig. 1. 第三十八張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月轉(zhuǎn)移灶的形成和生長(zhǎng)第三十九張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤侵襲和轉(zhuǎn)移相關(guān)基因Nm23基因NM23-H1 and NM23-H2 in humanNucleoside diphosphate

26、kinases (NDPKs) catalyze the exchange of -phosphate between nucleoside (and 2-deoxynucleoside) triphosphates and diphosphates with formation of a high-energy phosphohistidine intermediate(Parks and Agarwal 1973). They are encoded by the NME genes (also known as NM23).參與調(diào)節(jié)細(xì)胞內(nèi)微管系統(tǒng)的狀態(tài)高度表達(dá)nm23表現(xiàn)為低轉(zhuǎn)移屬性第四

27、十張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤侵襲和轉(zhuǎn)移相關(guān)基因腫瘤轉(zhuǎn)移相關(guān)基因mtal第四十一張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月腫瘤侵襲和轉(zhuǎn)移相關(guān)基因Tiam1 基因鼠T淋巴細(xì)胞瘤中克隆出來(lái)的基因。產(chǎn)物具有1591個(gè)氨基酸殘基，把蛋白質(zhì)錨定在質(zhì)膜上TIAM1 T-cell lymphoma invasion and metastasis 1 Homo sapiens Zhonghua Bing Li Xue Za Zhi. 2009 Apr;38(4):268-72.Overexpression of Tiam1 gene and its relationship with inv

28、asive and metastatic ability of nasopharyngeal carcinoma.Article in ChineseZhang XM, Ding Y, Chen JZ, Jin H, Yu LN, Li YF, Ding YQ.Currently, many GEFs, including Vav1, LARG, Bcr and T-lymphoma invasion and metastasis 1 (Tiam1), have been identified as oncogenes.第四十二張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月RESULTS: Tia

29、m1 over expression significantly increased the abilities of adhesion, migratory and invasion of C666-1 and CNE1 cells, comparing with that of the control untransfected cells (P 0.05).CONCLUSION: Tiam1 expression correlates with the invasion and metastasis of nasopharyngeal carcinoma cells.腫瘤侵襲和轉(zhuǎn)移相關(guān)基

30、因Tiam1 基因鼠T淋巴細(xì)胞瘤中克隆出來(lái)的基因。第四十三張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patientsYi Ding1, Bin Chen2, Shuang Wang3, Liang Zhao3, Juanzhi Chen3, Yanqing Ding3, Longhua Chen1* and Rongcheng Luo2*Int. J. Cancer: 124, 653658 (2009)2008 Wiley-L

31、iss, Inc.腫瘤侵襲和轉(zhuǎn)移相關(guān)基因Tiam1 基因鼠T淋巴細(xì)胞瘤中克隆出來(lái)的基因。第四十四張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月生長(zhǎng)因子通過(guò)Ras信號(hào)通路， 導(dǎo)致細(xì)胞增殖。轉(zhuǎn)染給NIH3T3細(xì)胞， 引起大量侵襲和轉(zhuǎn)移。Activated KrasG12D is associated with invasion and metastasis of pancreatic cancer cells through inhibition of E-cadherinBritish Journal of Cancer 104, 1038-1048 (15 March 2011) S Rachagani, S Senapati, S Chakraborty, M P Ponnusamy, S Kumar, L M Smith, M Jain and S K Batra 腫瘤侵襲和轉(zhuǎn)移相關(guān)基因Ras 基因包括H-ras， K-ras 和N-ras 三類， 第四十五張，PPT共四十七頁(yè)，創(chuàng)作于2022年6月Results: The KrasG12D knockdown cells exhibite