New use of poison - A's cream, B's honey

Frost and As2O3 frost, also known as Xinshi or Crane Top Red, as one of the eight famous poisons in history, Han Emperor Liuand Wu Dalang both died of this poison.
main component of antimony cream is arsenic trioxide.
arsenic in nature is mainly present in the form of male yellow (As4S4) and female yellow (As2S3), which are heated to a certain temperature and arsenic is oxidized in the air as2O3.
the ancient silver needle test was the sulphides in the insuperated cream.
As2O3 looks like a white frosty powder, so it's called frost.
As2O3 as an inorder drug with a fatality of 0.1-0.2g.
The discovery process of As2O3 in China: from poison to the treatment of leukemia drug ancient people cloud "to poison", "one thing down one thing", the drug power is too much into poison, the reverse control of poison can become a drug, thousands of years is not so.
As a model of poison attack, frost also has as a record of drug entry, Sun Siwei in the "preparation of thousands of gold parties" the first use of frost treatment of malaria, the Northern Song Dynasty, "Kaibao herb", Ming Dynasty Li Shizhen's "herb outline" have recorded the herb of the cream, late Ming and early Qing Dynasty Chen Shicheng with exercise after the cream treatment of syphilis.
western countries also recorded the use of potassium arsenate to treat leukemia in the 20th century, but it was not universally accepted.
In the 1970s, the state required urban doctors to visit farmers in the countryside, so it formed an "urban mobile medical team" to serve the countryside, stressing that "Chinese medicine is a great treasure trove that should be explored and improved".
during the tour, Han Taiyun of the First Hospital of Kazakhstan Medical University and others found that the "713" injections consisting of cream, light powder (chlorinated submersium) and crisps were effective for some tumors, but were more toxic.
1973, Zhang Tingdong and others identified the treatment of leukemia with a "Cancer Spirit 1" injection made up of cream and trace light powder.
1974, under the signature of the Chinese Medicine Department and the Inspection Department of the University of Kazakhstan, they published a paper that clearly stated that "Cancer Spirit 1" could treat a variety of leukemias, and that some acute leukemias could achieve complete remission (CR).
In 1979, Zhang Tingdong et al. published a paper in Heilongjiang Medicine, which identified as As2O3, the active ingredient of Cancer Spirit 1, and pointed out that it had the best effect on acute early childhood leukemia (APL), now M3 leukemia.
, domestic researchers first proposed the concept of As2O3 to treat M3 leukemia (APL).
, because domestic journals are mostly Chinese, domestic research results have not been known and accepted by the international medical community.
It wasn't until 1998, when the New England Journal of Medicine reported on studies at memorial Sloan-Kettering Cancer Center and Cornell Medical School that As2O3 was treated for APL patients and was almost completely relieved, that the international medical community widely accepted the therapeutic effects of As2O3 on APL.
As2O3's mechanism for treating APL (1) As2O3 induces APL cell differentiation and apoptosis Studies have shown that As2O3 can promote APL patient remission by inducing two different ways of cell differentiation and apoptosis (Figure 1).
high doses of As2O3 (0.5-2.0 μM) can induce apoptosis of leukemia: As2O3 and associated groups such as -based co-price reactions, such as mitochondrials Specific proteins such as Bcl-2 and PTPC reduce the mitochondrial membrane like ΔΨm, and the change in the likeness causes the release of cytochrome C, which activates the cystic winter enzyme cascade reaction and induces apoptosis.
changes in the membrane's likely film can also increase the release of mitochondrial ROS.
addition, As2O3 can also induce apoptosis in other ways, such as inhibiting the antioxidant enzyme GPx to further improve ROS levels, and promote apoptosis by inhibiting IK to further limit the activity of the cell survival factor NF-B.
low dose As2O3 (0.1-0.5μM) can induce differentiation and may be related to the regulation of camp pathways, nuclear subject activity, or histogenetic acetylation.
(2) As2O3 induces cancer protein PML and PML-RAR alpha degradation Whether low concentration induced differentiation or high concentration induced apoptosis, As2O3 works by co-price binding to the carcinogenic protein PML-RAR alpha/PML base to degrade PML-RAR alpha.
studies have shown that PML-RAR alpha fusion proteins are expressed in more than 98% of APL.
researchers, represented by Chen Wei, Chen Saiyi and Wang Zhenyi, carried out molecular mechanism research on As2O3 treatment of APL.
APL is a subtype (M3) of AML due to t (15;17) chromosomal susceptible, i.e. early granulocytic leukemia gene (PML) on chromosome 15 and chromosome 17 The vime acid lipolyst gene (RAR alpha) on the chromosome produces an abnormal PML-RAR alpha fusion gene that expresses the cancer protein PML-RAR alpha (Figure 2), which blocks cell differentiation and apoptosis.
, the t(15;17) chromosomal congeneration abnormal PML-RAR alpha fusion gene may be one of the main mechanisms of APL pathogenesis.
Chen and Chen, among others, proposed in the Science paper that As2O3 induces PML and PML-RAR alpha degradation mechanisms: arsenic agents by binding PML-RBCC protein or PML-RAR alpha protein zinc finger region on the cysteine residue, or binding to two zinc finger regions formed by cross-linking with two copolymers, such as Cys60, Cys60, Cys Cys72, Cys88, Cys91 (Figure 3) of s77, Cys80, and ZF2 induce changes in the composition of PML proteins or PML-RAR alpha fusion proteins (Figure 4), promote further oligomerization of PML-RAR alpha or PML proteins, enhance interaction with the ubibinase UFC9, or increase exposure to modified bits to promote THEMOization of these proteins.
lead to ubibinization and degradation of PML and PML-RAR alpha carcinogenic proteins, inducing APL leukemia cell differentiation and apoptosis.
paper proposes pmL and PML-RAR alpha carcinogenic proteins as direct targets for As2O3, which opens up new prospects for as2O3's application in future leukemia treatment.
Clinical Study of As2O3 Treatment of APL (1) Pilot Clinical Study of As2O3 Treatment of Relapse APL Domestic researchers using As2O3 to treat APL patients to obtain CR results has aroused the interest of researchers at Memorial Sloan-Kettering Cancer Center.
they launched a pilot study of APL patients who relapsed after chemotherapy for as2O3, an all-trans-cyclic acid (ATRA) and cyclic drug.
results showed that 11 out of 12 patients reached CR after treatment with As2O3 alone.
8 of the 11 respondents achieved molecular-level remission, and the expression of the APL cancer-causing gene, the PML-RAR alpha fusion gene, was not detected in the patient's body.
(2) Effectiveness of As2O3 in treating recurring APL Following the success of the pilot study, the researchers launched a larger open-label, multi-center one-arm trial (PLRXAS01) in which 40 patients with relapsed or refractic APL were treated with As2O3 (patients who had relapsed after receiving cyclocyc and TARA).
consistent with the expected results, 34 out of 40 patients (85%) achieved CR, and all patients who reached CR did not express the PML-RAR alpha fusion gene.
, 27 patients survived the post-follow-up, with a medium follow-up time of 484 days.
this critical trial provides strong data support for APL patients who are approved to treat ATRA/cyclic therapy with no response or recurrence of AS2O3.
(3) As2O3 has been widely used as a poison since ancient times.
arsenic is also classified as a carcinogen by the International Agency for Research on Cancer and the U.S. Environmental Protection Agency.
exposure to low arsenic levels increases the incidence of skin tumors, liver cancer, bladder cancer and lung cancer.
arsenic poisoning can cause symptoms such as peripheral neuropathy, cardiomyopathy and kidney failure.
but it is not appropriate to put aside the dose to talk about toxicity.
as a therapeutic drug, the patient has good tolerance when intravenously injecting As2O3 at a dose of 0.15 mg/kg/day.
can be observed as adverse reactions such as increased white blood cells, gastrointestinal conditions (e.g. nausea, vomiting, diarrhea), fatigue, fever, headache, cough and difficulty breathing, and no severe liver and kidney damage of magnitude 3 or above.
the long-term use of As2O3 combined ATRA to treat APL also does not occur secondary tumors.
but as2O3 treatment of APL can cause serious adverse reactions such as APL differentiation syndrome (APLDS) and electrostatization (ECG) abnormalities.
APLDS, also known as "vitamin acid syndrome," can occur during ATRA or As2O3 remission induction therapy, with symptoms including fever, breathing difficulties, low blood pressure, weight gain, acute renal failure, and lung immersion.
in key clinical trials (PLRXAS01) of As2O3 to treat APL, the rate of APLDS was 25% (10 cases), of which three patients had more severe APLDS.
, however, all patients with APLDS reached CR.
, the occurrence and severity of APLDS was similar to that of single-use As2O3 in clinical trials using ATRA to treat APL.
addition, As2O3 treatment of APL can lead to patient electrostatization abnormalities, including QT interstite extension and full room conduction block.
in the PLLXAS01 trial, 63% of patients observed an extension of the QT interstite.
other studies, As2O3 also led to other adverse heart events, including arrhythmic arrhythmics and myocardial infarction.
, electroenoxygrams and electrolyte monitoring should be carried out in a timely manner before and during arsenic treatment.
as2O3 applications for other diseases, in addition to being approved for the treatment of APL, a number of clinical studies are under way for other solid and hematomas.
the treatment of recurring refractic multiple myeloma (MM) with other drugs such as ascormic acid, mephedrone, dexamisund and boroniczomi alone or in association, clinical studies have tentatively demonstrated the effectiveness of the association.
the treatment of bone marrow growth abnormal syndrome (MDS) with As2O3 combined with salidamide and methicillin also showed clinical efficacy.
addition, clinical trials of As2O3 in the treatment of AML, co-interferon α (IFN alpha) in human T-cell lymphocytic virus type I (HTLV-I) in the form of AGADs (ATL) are also under way.
As2O3 treatment of a variety of solid tumors, including bladder cancer, glioma, breast cancer, liver cancer, cervical cancer, colorectal cancer, esophageal cancer, germ cell tumors, lung cancer and melanoma are also being studied.
it has been reported that as2O3 alone has limited clinical effects in hepatocellular carcinoma (HCC), melanoma and renal cell carcinoma, but As2O3 combination chemotherapy drugs have shown some therapeutic effect in osteosarcoma and Juven sarcoma.
As2O3 domestic research and development So far, the treatment of APL arsenic trioxide only injections and freeze-dried powder needles and other injection forms have been approved for clinical use, for other dosage forms such as oral solutions and capsule dosage forms are also under way.
other compound arsenic trioxide paste is used to treat pulp infestion.
until 2008, the domestic As2O3 injections were on the market, bringing hope of treatment to domestic APL patients.
domestic registered enterprises are mainly Beijing Shuangli and Hainan Zhonghua.
there are also Shanghai Yaojian Medical and Jinan Chuancheng Pharmaceuticals with 2.2 new drug applications for oral fluids are being reviewed and approved.
summary as2O3 for the treatment of APL, although the first discovery for Chinese medical workers, but due to historical reasons, did not apply for a patent application in time, also failed to bring As2O3 to market before foreign enterprises.
, however, we realize from this example that the active ingredients in China's valuable resources for Chinese medicine that may further improve human health may still be asleep and unedited.
to find new chemically structured drugs from traditional medicines and to discover new uses for existing natural products, which we will continue to explore for future generations.
, Li Runhong, Zhang Daqing. Scientific Research Monument of Chinese Medicine, Science and Technology Guide, 2015, 33 (20): 132-136. [2] N Engl J Med. 1998 Nov 5; 339(19):1341-8. [3] Zhang T D , Chen G Q , Wang Z G , et al. Arsenic trioxide, a therapeutic agent for APL. [J]. Oncogene, 2001, 20(49):7146-7153. [4] Emadi A , Gore S D . Arsenic Trioxide – An Old Drug Rediscovered[J]. Blood reviews, 2010, 24(4-5):191-199. [5] Zhang X , Yan X , Zhou Z , et al. Arsenic Trioxide Controls the Fate of the PML-RAR alpha Oncoprotein by Directly Binding PML[J]. Science, 2010. [6] Soignet SL, Frankel SR, Douer D, et al. United States mul