Paper help with Baozi# Biology - 生物学
s*l
1 楼
虽然我不拍西瓜，只挑个大的买，但是同一批西瓜怎么就一定是一样的呢。很明显，个
头大小就不一样，凭什么生熟就会一样。影响西瓜生熟的因素多了去了，就和影响大小
的因素多了去了一样。
头大小就不一样，凭什么生熟就会一样。影响西瓜生熟的因素多了去了，就和影响大小
的因素多了去了一样。
s*n
2 楼
CAR Signaling Domains Regulate T-Cell Exhaustion and Clinical Efficacy
http://cancerdiscovery.aacrjournals.org/content/5/7/OF20.long
Please send to [email protected]
/* */
Thanks a million!
http://cancerdiscovery.aacrjournals.org/content/5/7/OF20.long
Please send to [email protected]
/* */
Thanks a million!
b*a
3 楼
跟脑残较什么劲
v*a
4 楼
点击fulltext，只有这么多内容：
http://cancerdiscovery.aacrjournals.org/content/5/7/OF20.abstra
Chimeric antigen receptors (CAR) link antigen-binding domains with T-cell
signaling domains and represent potential anticancer agents. However, only
CARs targeting CD19 in hematologic malignancies have demonstrated
significant clinical efficacy. To identify the mechanisms underlying the
poor efficacy of CARs targeting other tumor antigens, Long and colleagues
compared the in vivo antitumor activity of CD19 CAR T cells harboring the
CD28 and CD3ζ signaling domains (CD19.28z) with that of GD2.28z CAR T cells
designed to target GD2-expressing solid tumors. In contrast to CD19.28z CAR
T cells, GD2.28z CAR T cells exhibited decreased persistence and failed to
inhibit tumor growth in mice. In ex vivo expansion studies, GD2.28z CAR T
cells showed indications of exhaustion, including increased rates of
apoptosis, higher expression of inhibitory receptors, and reduced cytokine
production. Unlike CD19.28z CARs, GD2.28z CARs exhibited basal levels of CD3
ζ phosphorylation, indicative of tonic signaling during ex vivo expansion.
Tonic GD2.28z CAR signaling induced early T-cell exhaustion independent of
antigen and was mediated by physical interactions between single-chain
variable fragments (scFv) that triggered CAR clustering at the cell surface.
Ex vivo tonic activation and T-cell exhaustion occurred to varying degrees
in all scFv-based CARs tested except the CD19 CAR. Furthermore, GD2 CARs
incorporating the 4-1BB costimulatory endodomain (GD2.BBz) rather than CD28
showed lower levels of exhaustion markers, increased persistence, and
greater antitumor efficacy in vivo. Expression of the GD2.BBz CAR resulted
in reduced expression of exhaustion-associated genes as well as altered
expression of genes involved in hypoxia, metabolism, and apoptosis compared
with T cells expressing the GD2.28z CAR, suggesting that 4-1BB may mitigate
exhaustion via multiple pathways. These studies provide a better
understanding of how CD19 CARs achieve antitumor efficacy and may explain
the increased persistence of CD19 CAR T cells that incorporate 4-1BB in
clinical trials compared with those harboring CD28.
http://cancerdiscovery.aacrjournals.org/content/5/7/OF20.abstra
Chimeric antigen receptors (CAR) link antigen-binding domains with T-cell
signaling domains and represent potential anticancer agents. However, only
CARs targeting CD19 in hematologic malignancies have demonstrated
significant clinical efficacy. To identify the mechanisms underlying the
poor efficacy of CARs targeting other tumor antigens, Long and colleagues
compared the in vivo antitumor activity of CD19 CAR T cells harboring the
CD28 and CD3ζ signaling domains (CD19.28z) with that of GD2.28z CAR T cells
designed to target GD2-expressing solid tumors. In contrast to CD19.28z CAR
T cells, GD2.28z CAR T cells exhibited decreased persistence and failed to
inhibit tumor growth in mice. In ex vivo expansion studies, GD2.28z CAR T
cells showed indications of exhaustion, including increased rates of
apoptosis, higher expression of inhibitory receptors, and reduced cytokine
production. Unlike CD19.28z CARs, GD2.28z CARs exhibited basal levels of CD3
ζ phosphorylation, indicative of tonic signaling during ex vivo expansion.
Tonic GD2.28z CAR signaling induced early T-cell exhaustion independent of
antigen and was mediated by physical interactions between single-chain
variable fragments (scFv) that triggered CAR clustering at the cell surface.
Ex vivo tonic activation and T-cell exhaustion occurred to varying degrees
in all scFv-based CARs tested except the CD19 CAR. Furthermore, GD2 CARs
incorporating the 4-1BB costimulatory endodomain (GD2.BBz) rather than CD28
showed lower levels of exhaustion markers, increased persistence, and
greater antitumor efficacy in vivo. Expression of the GD2.BBz CAR resulted
in reduced expression of exhaustion-associated genes as well as altered
expression of genes involved in hypoxia, metabolism, and apoptosis compared
with T cells expressing the GD2.28z CAR, suggesting that 4-1BB may mitigate
exhaustion via multiple pathways. These studies provide a better
understanding of how CD19 CARs achieve antitumor efficacy and may explain
the increased persistence of CD19 CAR T cells that incorporate 4-1BB in
clinical trials compared with those harboring CD28.
d*e
5 楼
吵了多少年了，还要吵。
在美国生活了不少年了，难道就没有吃到过不甜、不熟的瓜。
再说了，有人吃西瓜还讲究个脆沙瓤，你不挑的话，找谁买去。
工业化生产都还有次品呢，更何况西瓜。
在美国超市里买水果，不挑绝对是不行的。我有时候买回去的橘子、草莓不光是有压坏
的，甚至会有发霉的，这就是不挑的结果。
在美国生活了不少年了，难道就没有吃到过不甜、不熟的瓜。
再说了，有人吃西瓜还讲究个脆沙瓤，你不挑的话，找谁买去。
工业化生产都还有次品呢，更何况西瓜。
在美国超市里买水果，不挑绝对是不行的。我有时候买回去的橘子、草莓不光是有压坏
的，甚至会有发霉的，这就是不挑的结果。
t*l
6 楼
这只是对一篇NAT MED paper的评论or summary? 吧。。。
w*s
7 楼
那人是一加拿大小留，怀疑根本没来过美国。
【在 d***e 的大作中提到】
: 吵了多少年了，还要吵。
: 在美国生活了不少年了，难道就没有吃到过不甜、不熟的瓜。
: 再说了，有人吃西瓜还讲究个脆沙瓤，你不挑的话，找谁买去。
: 工业化生产都还有次品呢，更何况西瓜。
: 在美国超市里买水果，不挑绝对是不行的。我有时候买回去的橘子、草莓不光是有压坏
: 的，甚至会有发霉的，这就是不挑的结果。
【在 d***e 的大作中提到】
: 吵了多少年了，还要吵。
: 在美国生活了不少年了，难道就没有吃到过不甜、不熟的瓜。
: 再说了，有人吃西瓜还讲究个脆沙瓤，你不挑的话，找谁买去。
: 工业化生产都还有次品呢，更何况西瓜。
: 在美国超市里买水果，不挑绝对是不行的。我有时候买回去的橘子、草莓不光是有压坏
: 的，甚至会有发霉的，这就是不挑的结果。
s*n
8 楼
多谢多谢！
s*e
9 楼
买西瓜不拍的人生活没情趣
t*Q
10 楼
拍西瓜跟拍女人屁股一样有感觉。
【在 s*******e 的大作中提到】
: 买西瓜不拍的人生活没情趣
【在 s*******e 的大作中提到】
: 买西瓜不拍的人生活没情趣
c*t
11 楼
买榴莲不用拍
s*l
12 楼
赞
吃的感觉呢？
【在 t*Q 的大作中提到】
: 拍西瓜跟拍女人屁股一样有感觉。
吃的感觉呢？
【在 t*Q 的大作中提到】
: 拍西瓜跟拍女人屁股一样有感觉。
b*a
13 楼
还是西瓜甜
【在 s****l 的大作中提到】
: 赞
: 吃的感觉呢？
【在 s****l 的大作中提到】
: 赞
: 吃的感觉呢？
u*n
14 楼
热，那只是个坑而已。我都懒得会。国内去瓜田里卖瓜，瓜农也是在一片地里挑好的。
【在 b*****a 的大作中提到】
: 跟脑残较什么劲
【在 b*****a 的大作中提到】
: 跟脑残较什么劲
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