https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.

/pdf/apoptosis-a-review-of-programmed-cell-death-ly0ozrc0t6.pdf

Apoptosis: A Review of Programmed Cell Death

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

/pdf/the-blockade-of-immune-checkpoints-in-cancer-immunotherapy-j2cp4ba5s9.pdf

The blockade of immune checkpoints in cancer immunotherapy

The intracellular receptor of rapamycin, a macrolide antibiotic produced by Streptomyces hygroscopicus, is FKBP12 (FK506-binding protein). The rapamycin-FKBP12 complex, in turn, specifically interacts with the mammalian target of rapamycin (mTOR), to potently inhibit mTOR signaling to downstream targets. Cumulative evidence supports the hypothesis that mTOR acts as a master switch of cellular catabolism and anabolism. In addition, mTOR has been recently found to have profound effects on the control of apoptosis. MTOR is a serine/threonine kinase which signals to downstream effectors, either through direct phosphorylation or via the inhibition of the phosphatase PP2A. Under normal circumstances, in the presence of growth factor and nutrients, mTOR is constitutively activated. This activation is achieved, in part, through the insulin receptor or insulin-like growth factor receptor pathways, via a cascade that involves the activation of phosphatidylinositide-3-kinase (PI3K), then phosphatidyl inositol-3,4,5 phosphate-mediated act ivat ion of Akt/PKB-mediated phosphorylation of mTOR. Deacetylated tRNA species accumulating as a result of amino acid shortage may act as negative regulators of mTOR, through a pathway that remains to be elucidated. Moreover, the c-Abl protein tyrosine kinase phosphorylates mTOR and inhibits its action (Figure 1).

Mammalian target of rapamycin (mTOR): pro- and anti-apoptotic.

Mammalian cells harness autophagy to eliminate physiological byproducts of metabolism and cope with microenvironmental perturbations. Moreover, autophagy connects cellular adaptation with extracellular circuitries that impinge on immunity and metabolism. As it links transformed and non-transformed components of the tumour microenvironment, such an autophagic network is important for cancer initiation, progression and response to therapy. Here, we discuss the mechanisms whereby the autophagic network interfaces with multiple aspects of malignant disease.

The autophagic network and cancer

https://www.cell.com/cell/pdf/S0092-8674(20)31606-8.pdf

Hallmarks of health.

https://www.nature.com/articles/s41422-022-00653-7.pdf

Guido Kroemer

Papers

Mammalian target of rapamycin (mTOR): pro- and anti-apoptotic.

The autophagic network and cancer

Hallmarks of health.

Cuproptosis: a copper-triggered modality of mitochondrial cell death

Molecular mechanisms of regulated necrosis