This group of Chinese doctors turned the "deadly" poison into a "cure" medicine

In 2017, the two academicians Chen Zhu and Chen Saijuan, well-known domestic leukemia research experts, published a special article entitled "Poisoning the Devil" in Cell magazine, introducing the story behind their research and development of the "Poisoning the Devil" arsenic treatment for leukemia with their own scientific research experience.
He also pointed out that their scientific career has benefited a lot from the integration of Chinese and Western wisdom
.

Academicians Chen Zhu and Chen Saijuan at Shanghai Institute of HematologyPoisoning the Devil.

In 2017, the two academicians Chen Zhu and Chen Saijuan, well-known domestic leukemia research experts, published a special article entitled "Poisoning the Devil" in Cell magazine, introducing the story behind their research and development of the "Poisoning the Devil" arsenic treatment for leukemia with their own scientific research experience.
He also pointed out that their scientific career has benefited a lot from the integration of Chinese and Western wisdom
.
Academician Chen Zhu and Chen Saijuan at Shanghai Institute of HematologyPoisoning the Devil.
Cell.
2017 Feb 9;168(4):556-560.
doi: 10.
1016/j.
cell.
2017.
01.
029.
As we all know, arsenic, also known as arsenic trioxide (ATO) ), according to historical records, the poison arsenic is one of the ancient world, as the "King of poison" .
How can such a poison that everyone avoids become a good medicine to fight cancer? In fact, arsenic is also one of the oldest drugs in the world .
The "Huang Di Nei Jing" has recorded that arsenic can be used to treat periodic fever symptoms, and Sun Simiao has also used drugs containing realgar, orpiment and arsenic to treat malaria .
Similarly, Western Hippocrates also proposed for the first time the use of arsenic sulfide paints such as realgar and orpiment to treat ulcers .
China began the exploration of arsenic treatment for leukemia in the 1970s .
At that time, Han Taiyun , a pharmacist at the First Affiliated Hospital of Harbin Medical University, accidentally discovered that folk remedies containing arsenic trioxide (ATO), mercury chloride, or toad powder had an effect on some cancer patients.
    
  
Afterwards, he used the same ingredients to reform and obtain "Ailing Injection", and further discovered that ATO and mercury injections have potential curative effects on myeloid leukemia
.
However, because the mechanism of ATO was not yet clear at the time, it was not widely promoted
.
Acute promyelocytic leukemia (APL), also known as the M3 subtype of acute myeloid leukemia (AML-M3), accounts for 10% of all AML cases .
APL used to be one of the most deadly leukemias.
It is a heavy burden caused by blocking the differentiation of the bone marrow in the promyelocytic stage of the white blood cell blasts, causing hemorrhagic syndrome .
In the 1970s, the mainstream treatment method was a combination of anthracyclines and cytarabine, but chemotherapy often aggravated bleeding and caused high early mortality .
Since then, Academician Wang Zhenyi of the Shanghai Institute of Hematology pioneered the use of all-trans retinoic acid (ATRA) to treat promyelocytic leukemia and achieved great clinical effects of APL, which can make the complete remission rate of the disease exceed 90%, bringing patients Gave new hope .
Afterwards, at a meeting, Chen Saijuan learned about the use of ATO in the treatment of APL patients by colleagues at Harbin Medical University in the early years, and came up with the idea of ​​whether ATRA and ATO can be combined .
Through years of study and practice, they discovered that ATO may trigger the differentiation and apoptosis of acute promyelocytic leukemia cells by targeting the oncogenic driver gene PML-RARα of acute promyelocytic leukemia, laying the foundation for clinical application .
With the support of the new theory, researchers initiated a clinical trial of ATRA combined with ATO for the first-line treatment of newly diagnosed APL patients in 2000 .
The trial has produced exciting clinical follow-up results: among patients receiving combination therapy, the 5-year recurrence-free survival rate was as high as 94.
8%, and the overall survival rate of patients with complete remission was as high as 97.
4%.
  
  .
( Can only live for 5 years? Most people mistake the "5-year survival rate" and only live for 5 years? Most people mistake the "5-year survival rate" ) (click here to view the five-year survival rate) Follow-up item The large multicenter clinical trial recruited 535 newly diagnosed APL patients, and their 5-year disease-free survival rate exceeded 90% .
This miraculous synergistic response has been confirmed by hematologists and oncologists worldwide .
In 2014, ATRA/ATO combination therapy was recommended by NCCN (National Comprehensive Cancer Network) as the preferred treatment for APL .
Looking back on their scientific research careers, academicians Chen Zhu and Chen Saijuan felt that they had benefited a lot from the ancient wisdom of China and the West.
In particular, the ancient Chinese thought of "fighting drugs with poison" taught them how to treat problems dialectically.
At the same time, modern Western scientific research training, advanced science Technology also helps them understand each step of disease progression at the molecular level, so that they can make scientific breakthroughs in a more targeted manner .
Until now, in the medical world, it has long been news that arsenic can treat acute promyelocytic leukemia (APL), but "confronting poison with poison" is by no means that simple .
In December last year, the research team of Professor Lu Min from Ruijin Hospital of Shanghai Jiaotong University published a study in Cancer Cell that revealed the relationship between arsenic and the "strongest" tumor suppressor gene p53 .
                 Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site.
Cancer Cell  
 
 
                                                      (2020).
https://doi.
org/10.
1016/j.
ccell.
2020.
11.
013 The study pointed out that arsenic trioxide can rescue the strongest tumor suppressor gene p53 .
Data shows that at least 50% of cancer patients have p53 mutations or loss of function .
In this study, the arsenic atoms in the arsenic could be inserted into the DNA binding domain of the structurally mutated p53 protein, which in turn restored the transcriptional activity of the p53 protein with the structural mutation of R175H, and only a small dose (0.
1ug/ml) ) Can be achieved .
In this study, the researchers screened 4 compounds from 20861 small molecules in the DTP database.
Through the detection of the antibody PAb1620 that preferentially recognizes the folded p53 protein, it was found that arsenic and KAsO2 promoted the folding of the R175H structural mutation p53 protein.
Role .
Subsequently, the researchers discovered that arsenic stabilizes the structural mutation of the p53 fold by covalent bonding .
And compared with other compounds, the stabilizing effect of arsenic far exceeds that of other compounds .
It was further discovered that the crystal structure of the arsenic-binding p53 mutant revealed a hidden allosteric site involving three arsenic-coordinating cysteines distal to the zinc-binding site in the DNA binding domain .
The combination of arsenic stabilizes the spiral structure of the DNA-bound loop sheet and the entire β sandwich fold, so that the p53 mutant has thermal stability and transcriptional activity .
In cell and mouse xenograft models, ATO reactivates mutant p53 to suppress tumors .
It can be seen that  
 
   Using arsenic to target p53 mutations may become a new idea for anti-tumor therapy, providing a mechanism basis for widely applicable and personalized cancer treatments
.
As two academicians Chen Zhu and Chen Saijuan stated in the article, the road to "contend with poison" to treat diseases is still very long, and we are just beginning now .
References: References: 1.
Poisoning the Devil.
Cell.
2017 Feb 9;168(4):556-560.
doi: 10.
1016/j.
cell.
2017.
01.
029.
2.
Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site.
Cancer Cell (2020).
https://doi.
org/10.
1016/j.
ccell.
2020.
11.
013 Leave a message here