w***r
发帖数: 709 | | f****y
发帖数: 104 | 2 你如何阻止DNA突变？
[在 whour (ffffffffff) 的大作中提到：]
：根据现有机理的 | w***r
发帖数: 709 | 3 Ventura et al. (2007) and Xue et al. (2007) suggest that restoring p53
function alone is sufficient to cause regression of several different tumor
types in mice and thus might represent a potent therapeutic strategy to
treat certain human cancers.
Martins et al. (2006) also demonstrate that restoration of p53 activity
results in tumor regression but add the sobering caveat that tumors may be
able to quickly generate resistance by finding other ways to disrupt the p53
pathway.
比如加上inducible p53在必须基因附近。 | w***r
发帖数: 709 | 4 改变抗原递呈，让细胞可把常见突变肽呈现到表面，帮助免疫认别。
肿瘤突变多，提高递呈效率，可以增强抗肿瘤免疫？ | w***r
发帖数: 709 | 5 表达某种受体蛋白在所有细胞表面，以增加得病时基因治疗的效率
endogenous crispr cas9,受体导入rna,癌突变随意切
Uptake of extracellular double-stranded RNA by SID-2.
McEwan DL1, Weisman AS, Hunter CP.
Author information
Abstract
Ingested dsRNAs trigger RNA interference (RNAi) in many invertebrates,
including the nematode Caenorhabditis elegans. Here we show that the C.
elegans apical intestinal membrane protein SID-2 is required in C. elegans
for the import of ingested dsRNA and that, when expressed in Drosophila S2
cells, SID-2 enables the uptake of dsRNAs. SID-2-dependent dsRNA transport
requires an acidic extracellular environment and is selective for dsRNAs
with at least 50 base pairs. Through structure-function analysis, we
identify several SID-2 regions required for this activity, including three
extracellular, positively charged histidines. Finally, we find that SID-2-
dependent transport is inhibited by drugs that interfere with vesicle
transport. Therefore, we propose that environmental dsRNAs are imported from
the acidic intestinal lumen by SID-2 via endocytosis and are released from
internalized vesicles in a secondary step mediated by the dsRNA channel SID-
1. Similar multistep mechanisms may underlie the widespread observations of
environmental RNAi. | w***r
发帖数: 709 | | T*G
发帖数: 600 | 7 Restoring P53 那些灌水的paper就是个joke, p53做了这么多年，出了一个抗癌药吗，
曾经天朝的今又生就不要提了。头都被抓进去了
tumor
p53
【在 w***r 的大作中提到】
: Ventura et al. (2007) and Xue et al. (2007) suggest that restoring p53
: function alone is sufficient to cause regression of several different tumor
: types in mice and thus might represent a potent therapeutic strategy to
: treat certain human cancers.
: Martins et al. (2006) also demonstrate that restoration of p53 activity
: results in tumor regression but add the sobering caveat that tumors may be
: able to quickly generate resistance by finding other ways to disrupt the p53
: pathway.
: 比如加上inducible p53在必须基因附近。
| w***r
发帖数: 709 | 8 Restore 一个蛋白的功能太难了，肿瘤一个新的突变，就把药废了。
但是进行基因组改造是不一样的东西
【在 T*G 的大作中提到】
: Restoring P53 那些灌水的paper就是个joke, p53做了这么多年，出了一个抗癌药吗，
: 曾经天朝的今又生就不要提了。头都被抓进去了
:
: tumor
: p53
| f****y
发帖数: 104 | 9 你说的都是得了癌症如何治疗，如果你说的都可实现的话，那么人得不得癌症都无所谓
了。
而且基因组改造，不还是改DNA吗？只要DNA突变，什么改造不还是没意义？
我比较悲观，我觉得癌症是发展出多细胞生物的必然代价，无法避免。
[在 whour (ffffffffff) 的大作中提到：]
：Restore 一个蛋白的功能太难了，肿瘤一个新的突变，就把药废了。
：但是进行基因组改造是不一样的东西
：........... | w***r
发帖数: 709 | 10 以前没有疫苗的时候，很多疾病看起来也是无法避免的。
基因改造可以让人100年之内不得癌已经足够了。
不同寿命的生物，尽管基因相似，一定有各自独特的抗癌机理。dna突变率只是一部分。
【在 f****y 的大作中提到】
: 你说的都是得了癌症如何治疗，如果你说的都可实现的话，那么人得不得癌症都无所谓
: 了。
: 而且基因组改造，不还是改DNA吗？只要DNA突变，什么改造不还是没意义？
: 我比较悲观，我觉得癌症是发展出多细胞生物的必然代价，无法避免。
: [在 whour (ffffffffff) 的大作中提到：]
: ：Restore 一个蛋白的功能太难了，肿瘤一个新的突变，就把药废了。
: ：但是进行基因组改造是不一样的东西
: ：...........
| | | w***r
发帖数: 709 | | n***y
发帖数: 114 | | w***r
发帖数: 709 | 13 "Contact inhibition, a powerful anticancer mechanism,
这个contact inhibition 是癌症研究早期，基于在体外细胞培养的一个人造概念。
个人觉得和发育时，器官的大小控制有关，也许hippo会影响这个东西。
和体内癌症发生关系可能不直接。这种古董概念还有transform,immortalization
Bob Weinberg那些人早期的东西。
我觉得这个mol rat 代谢独特，或干细胞维护不同与一般鼠辈 | v*******e
发帖数: 11604 | 14 easy, make 20 copies of P53 gene, place one on each chromosome. | w***r
发帖数: 709 | 15 "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant
and
age normally.
García-Cao I(1), García-Cao M, Martín-Caballero J, Criado LM, Klatt P,
Flores JM,
Weill JC, Blasco MA, Serrano M.
Author information:
(1)Spanish National Center of Biotechnology, Department of Immunology and
Oncology, Campus de Cantoblanco, Madrid E-28049, Spain.
The tumor suppressor p53 is critical in preventing cancer due to its ability
to
trigger proliferation arrest and cell death upon the occurrence of a variety
of
stresses, most notably, DNA damage and oncogenic stress. Here, we report the
generation and characterization of mice carrying supernumerary copies of the
p53
gene in the form of large genomic transgenes. Prior to this, we demonstrate
that
the p53 transgenic allele (p53-tg), when present in a p53-null genetic
background, behaves as a functional replica of the endogenous gene. "Super
p53"
mice, carrying p53-tg alleles in addition to the two endogenous alleles,
exhibit
an enhanced response to DNA damage. Importantly, "super p53" mice are
significantly protected from cancer when compared with normal mice. Finally,
in
contrast to previously reported mice with constitutively active p53, "super
p53"
mice do not show any indication of premature aging, probably reflecting the
fact
that p53 is under normal regulatory control. Together, our results prove
that
cancer resistance can be enhanced by a simple genetic modification and in
the
absence of undesirable effects.
【在 v*******e 的大作中提到】
: easy, make 20 copies of P53 gene, place one on each chromosome.
| w***r
发帖数: 709 | 16 有文献认为太多p53导致早衰，老鼠寿命短，所以看不出来？ | v*******e
发帖数: 11604 | 17
DNA damage才会导致早衰，若没有DNA damage，P53不发动的，光是多p53 gene不会导
致早衰。
【在 w***r 的大作中提到】
: 有文献认为太多p53导致早衰，老鼠寿命短，所以看不出来？
| l********e
发帖数: 415 | 18 inducible DTA, 28岁打一针. 癌症发病率下降至目前水平的0.1%以内.
【在 w***r 的大作中提到】
: 根据现有机理的
| w***r
发帖数: 709 | 19 用啥表达这个dta
【在 l********e 的大作中提到】
: inducible DTA, 28岁打一针. 癌症发病率下降至目前水平的0.1%以内.
| w***r
发帖数: 709 | 20 1. Nature. 2002 Jan 3;415(6867):45-53.
p53 mutant mice that display early ageing-associated phenotypes.
Tyner SD(1), Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu
X,
Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A,
Donehower LA.
Author information:
(1)Cell and Molecular Biology Program, Baylor College of Medicine, Houston,
TX
77030, USA.
Comment in
Nature. 2002 Jan 3;415(6867):26-7.
The p53 tumour suppressor is activated by numerous stressors to induce
apoptosis,
cell cycle arrest, or senescence. To study the biological effects of altered
p53
function, we generated mice with a deletion mutation in the first six exons
of
the p53 gene that express a truncated RNA capable of encoding a carboxy-
terminal
p53 fragment. This mutation confers phenotypes consistent with activated p53
rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced
resistance to
spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m
mice
age, they display an early onset of phenotypes associated with ageing. These
include reduced longevity, osteoporosis, generalized organ atrophy and a
diminished stress tolerance. A second line of transgenic mice containing a
temperature-sensitive mutant allele of p53 also exhibits early ageing
phenotypes.
These data suggest that p53 has a role in regulating organismal ageing.
【在 v*******e 的大作中提到】
:
: DNA damage才会导致早衰，若没有DNA damage，P53不发动的，光是多p53 gene不会导
: 致早衰。
| | | v*******e
发帖数: 11604 | 21 你这个和我说的没什么关系。
Lu
,
【在 w***r 的大作中提到】
: 1. Nature. 2002 Jan 3;415(6867):45-53.
: p53 mutant mice that display early ageing-associated phenotypes.
: Tyner SD(1), Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu
: X,
: Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A,
: Donehower LA.
: Author information:
: (1)Cell and Molecular Biology Program, Baylor College of Medicine, Houston,
: TX
: 77030, USA.
| w***r
发帖数: 709 | 22 p53 水平过高，老鼠会有早衰现象,在自然生长的条件下。
对dna damage 过于敏感，不利干细胞扩增，组织修复。
除了 DNA 损伤，其他stress 也可以激活p53.
【在 v*******e 的大作中提到】
: 你这个和我说的没什么关系。
:
: Lu
: ,
| v*******e
发帖数: 11604 | 23 copy多不等于水平高，这个P53的表达有调控的。copy多可以防止某几个出mutation失
效。你想要做出不得癌症的人类，增加P53雍余度（不是增加表达水平）是个很好的方法
【在 w***r 的大作中提到】
: p53 水平过高，老鼠会有早衰现象,在自然生长的条件下。
: 对dna damage 过于敏感，不利干细胞扩增，组织修复。
: 除了 DNA 损伤，其他stress 也可以激活p53.
| w***r
发帖数: 709 | 24 Super p53 mice 是多一个copy. P53 显然值得一试。
肿瘤还是可以丢失arf把p53解决掉
方法
【在 v*******e 的大作中提到】
: copy多不等于水平高，这个P53的表达有调控的。copy多可以防止某几个出mutation失
: 效。你想要做出不得癌症的人类，增加P53雍余度（不是增加表达水平）是个很好的方法
| m********a
发帖数: 12601 | 25 这个不难吧，直接设定一个20年的hard cutoff life time，20岁生日一到，直接嗝屁
得癌症的主要原因是活太久，超过了设计寿命了 | w***r
发帖数: 709 | 26 You must be long overdue :)
【在 m********a 的大作中提到】
: 这个不难吧，直接设定一个20年的hard cutoff life time，20岁生日一到，直接嗝屁
: 得癌症的主要原因是活太久，超过了设计寿命了
|
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