Author: Sihua Gao
Abstract:
Primary hepatocellular carcinoma is one of the most common malignant tumors with high mortality, especially in the middle and late stages; there is still no effective treatment in modern medicine. Based on the clinical and pharmacological studies on the treatment of advanced primary hepatocellular carcinoma with Hepatocellular Carcinoma Powder, this paper expounds the pathogenesis and pathogenesis of hepatocellular carcinoma from the perspective of liver and spleen, from the inside and outside, from the vital deficiency with phlegm, dampness, heat, blood stasis and toxicity; balancing the righteousness and the evil, and considering the combination of Chinese and Western medicine, taking into account the factors related to the viscera and the various evils to select drugs; focusing on the efficacy, thinking about new drugs, high standards, and strict requirements for experimental research and clinical research of traditional Chinese medicine for the treatment of primary hepatocellular carcinoma. And the method is designed to explore and develop new Chinese medicines for the treatment of primary hepatocellular carcinoma with good effect.
Primary hepatocellular carcinoma (PLC) is one of the most common malignant tumors with high mortality in China. Although in recent years, with the advancement of modern medical imaging diagnostic techniques and the popularity of tumor marker examinations, early diagnosis has become possible. Moreover, with the rapid development of surgical therapy (OP), hepatic artery embolization therapy (TAE), B-guided anhydrous alcohol injection therapy (PEI), radiation therapy (IR) and other local treatment methods for primary hepatocellular carcinoma, the effective rate and survival rate have been improved continuously, but there is still no effective treatment for advanced hepatocellular carcinoma. Therefore, it is an important task for us to give full play to the advantages of traditional Chinese medicine and explore effective treatment for advanced primary hepatocellular carcinoma. In recent years, the clinical and pharmacological studies on the treatment of advanced primary hepatocellular carcinoma with Hepatocellular Carcinoma Powder have been carried out. The research ideas and methods are briefly introduced to seek the same principle.
1. We should understand the etiology and pathogenesis of hepatocellular carcinoma from the perspective of liver and spleen, from the inside and outside, from the vital deficiency with phlegm, dampness, heat, blood stasis and toxicity.
In addition to the obvious carcinogenic effect of aflatoxin B1 and other chemicals related to the incidence of liver cancer, modern medical research in recent years has also found that the incidence of primary hepatocellular carcinoma is related to the following factors.
1.1 Hepatitis Virus
Persistent infection of hepatitis virus is a high risk factor for primary hepatocellular carcinoma. Persistent infection of hepatitis C virus (HCV) is more important than that of hepatitis B virus (HBV). According to the data of the population dynamic survey of the Ministry of Health, Labour and Welfare in Japan, of the 2.4 million people who had a history of HBV infection in 1988, about 6,000 died of hepatocellular carcinoma, of the 1.4 million people who had a history of HCV infection, about 14,000 died of hepatocellular carcinoma. It is confirmed that the mortality rate of HCV infection is four times higher than that of HBV infection. According to the results of the WHO epidemiological survey of hepatocellular carcinoma (see table below), although the infection rates of HBV and HCV vary among hepatocellular carcinoma patients in various countries, but more than 80%-90% of the patients with hepatocellular carcinoma have hepatitis virus infection, which indicates that the persistent infection of hepatitis virus is the main cause of hepatocellular carcinoma. In recent years, the improvement of medical conditions has led to an increase in blood transfusions, and the infection of HCV has a tendency to gradually exceed HBV infection and become a major cause of hepatocellular carcinoma.
1.2 Androgen
The level of androgen is closely related to the occurrence of hepatocellular carcinoma. Animal experiments have proved that male animals are more susceptible to hepatocellular carcinoma than female animals. They injected the same dose of carcinogen DEN into male and female mice respectively and found that almost 100% of male mice developed hepatocellular carcinoma, while almost 100% of female mice did not develop hepatocellular carcinoma. The incidence of hepatocellular carcinoma in male mice whose gonads were removed under the same conditions was only 18.7%. Thus, it is confirmed that androgen is closely related to the occurrence and proliferation of hepatocellular carcinoma, and it is considered that androgen is not a direct carcinogen. But on the one hand, it promotes the accumulation of intrahepatic bile and prolongs the contact time between carcinogens in bile and hepatocytes, thus indirectly creating an environment prone to the occurrence of hepatocellular carcinoma; on the other hand, it promotes the proliferation of hepatocytes that have received carcinogens.
1.3 Tobacco and alcohol hobbies
Excessive smoking and drinking should be considered as a risk factor for hepatocellular carcinoma. Epidemiological investigations have found that the incidence of male hepatocellular carcinoma is significantly higher than that of females, and the ratio of male to female is about 9:1 to 7:2. A follow-up survey of 9,000 HBsAg-positive healthy carriers abroad for several years shows that although they have the same experience of HBV infection, the incidence of hepatocellular carcinoma in heavy drinkers and smokers is many times higher than that in light drinkers and smokers. Therefore it is believed that HBV and HCV are genes, and the difference between men and women in tobacco and alcohol brings about the difference between men and women in the incidence and mortality of hepatocellular carcinoma. And excessive drinking and smoking should be regarded as a risk factor for hepatocellular carcinoma.
1.4 Etiology of Traditional Chinese Medicine
According to the theoretical analysis of traditional Chinese medicine, its etiology includes both internal and external aspects. Internal causes are mainly spleen dysfunction caused by fatigue and spleen injury, or liver dysfunction caused by emotional depression. External causes are mainly wet, heat and toxic pathogens intruding into liver, gallbladder, spleen and stomach, or excessive tobacco and alcohol generate dampness, heat and toxicity which bind in liver, gallbladder, spleen and stomach. The pathogenesis is vital deficiency and evil prevails. And the deficiency mostly lies in liver and spleen. The evil is mainly sputum, dampness, heat, phlegm and toxicity. Most of them are caused by spleen failing to dissipate dampness or external dampness invades. Dampness gather to generate phlegm, heat and toxicity which bind in liver and gallbladder; or stagnation of liver-qi, stagnation of qi and blood stasis result in application of heat toxicity, or dampness-heat toxicity invades in the liver and gallbladder directly; while excessive dampness is prone to insult the liver, qi stagnation and blood stasis in the liver and gallbladder can result in failing to dredge soil, or dampness and heat in the liver and gallbladder is prone to overwhelm the function of spleen, and dampness, phlegm, heat, blood stasis and toxicity, which are mutually causal, thus aggravating the development of the disease, and the various pathogens bind in the liver to form cancer. In the middle and late stage of the disease, the syndrome of yin deficiency and deficiency of body fluid often appears as ascites due to liver dysfunction and dys-splenism.
Therefore, the pathogenesis of advanced hepatocellular carcinoma should be analyzed from qi-yin deficiency of liver and spleen embracing all evils inside.
2. Balancing the righteousness and the evil, and considering the combination of Chinese and Western medicine, taking into account the factors related to the viscera and the various evils to select drugs
In recent years, there have been many studies on the treatment of cancer, including those who advocate clearing away heat and detoxification, those who advocate promoting blood circulation and removing blood stasis, those who advocate resolving phlegm and dampness, those who advocate strengthening the body resistance, those who advocate resolving hard lump and those who advocate fighting fire with fire. Each of these views has its own merits. Based on the above understanding of the pathogenesis of middle and late stage hepatocellular carcinoma, we learn from all the advantages and take into account the spirit of both strengthening the body resistance and eliminating pathogenic factors. We not only fully consider the relationship of mutual use and mutual restriction between the liver and the spleen, qi and yin, but also fully consider the characteristics of reciprocal causation and vicious circle of phlegm, dampness, heat, blood stasis and toxicity. Based on the principle of nourishing liver, soothing liver and strengthening spleen, clearing away heat and detoxifying, resolving phlegm and softening hard masses, eliminating blood stasis and dispersing knots to incite water circulation, we selected drug to compose the prescription of “Hepatocellular Carcinoma Powder” for the treatment of advanced primary hepatocellular carcinoma. In the process of drug screening, besides strictly following the theory of traditional Chinese medicine, according to the characteristics of meridian tropism and efficacy of drugs and the requirements of composition theory, we also combine the etiology and pathology of hepatocellular carcinoma with the knowledge of western medicine, and according to modern pharmacological research, from the point of view of different anticancer effects of killing cancer cells, or inhibiting the growth of cancer cells, or enhancing the body's immune function, or containing microelements closely related to cancer treatment, and adverse factors that may be caused by drugs to promote the proliferation of hepatocytes have been comprehensively considered. Under the same conditions, the former is chosen to avoid the latter. For example, when choosing the drugs of invigorating the spleen and qi, both astragalus membranaceus and ginseng are sweet and warm to enter the lungs and spleen meridians can greatly invigorate the qi of the lung and spleen. The spleen is the essence of the acquired life, the lung dominates the qi of the whole body, so to nourish the lung and spleen can strengthen the whole body's qi.
From the point of view of the location of hepatocellular carcinoma, liver retains evils, while lung restrains liver and spleen is restrained by liver. According to viscera theory, nourishing the lung and spleen can help to restrict the liver, and modern pharmacological studies have proved that both drugs can protect the liver and enhance the anti-cancer effect of human immune function. However, Astragalus membranaceus can not only invigorate qi, but also induce diuresis and expel toxicity and generate muscles. "To expel extravasated blood among five viscera" (<<Bie Lu>>), "to break plot and cure scrofula"(<<Ri Hua Zi>>), it can not only strengthen the body resistance and dispel evils which is beyond the scope of ginseng; and Astragalus also has the function of reducing hepatitis B surface antigen, containing astragalus polysaccharide to resist cancer through immune activation, containing quercetin to inhibit the growth of cancer cells, the contained microelement selenium also has anti-cancer effect, and so on. The treatment-related effect of hepatocellular carcinoma is also better than that of ginseng. In addition, modern pharmacological studies have confirmed that ginseng has a gonadotropin effect, which seems to be unfavorable for the treatment of hepatocellular carcinoma, so we choose Astragalus instead of ginseng. Another example is that Sophora flavescens and Coptis chinensis are antidotes for clearing heat and drying dampness, and both enter the meridians of heart, liver, stomach and large intestine. Modern pharmacological research has confirmed that both drugs have anti-cancer effects, but Sophora flavescens is better than Coptis chinensis in the effects of "dominating cardiac and abdominal qi, accumulation of plot, jaundice" ("Ben Jing") and promoting diuresis and expelling water, and experiments proves that its anti-cancer effect is also better. The screening of other medicines is also the same. It is always based on the theory and principle of compatibility of traditional Chinese medicine prescriptions, combined with the pathological characteristics of hepatocellular carcinoma, from the perspective of combination of disease differentiation and syndrome differentiation, and modern pharmacological research is also taken into account to select drugs and compose prescriptions. We should not only follow the theoretical system of traditional Chinese medicine, highlight the characteristics of traditional Chinese medicine, but also absorb modern science and embody the idea of combining traditional Chinese and Western medicine.
3. Focusing on the efficacy, thinking about new drugs, high standards, and stricting requirements for experimental research and clinical research
The purpose of experimental and clinical research of the drugs for hepatocellular carcinoma is to explore new ways for the treatment of hepatocellular carcinoma and to develop effective new drugs for hepatocellular carcinoma treatment. Therefore, the research plan and research content should be carried out in strict accordance with the technical requirements for pharmacological research, toxicological research and clinical research of new drugs stipulated in the "Approval Measures for New Drugs" formulated and issued by the Ministry of Health of the People's Republic of China. Pharmacodynamic studies focused on the effect of expelling evils such as anti-tumor effects on transplanted animal tumors and the inhibition of tumor cell growth in vitro, and the rehabilitation effects such as the effects on immune function of normal animals, the effects on immune function of tumor-bearing animals, the effects of chemotherapy on immunosuppressive function of animals, and the experimental studies on synergistic and attenuating effects. The clinical research strictly follows the case selection criteria, observation indicators, and efficacy judgment criteria prescribed by the clinical research guidelines for the treatment of primary hepatocellular carcinoma issued by the Ministry of Health of the People's Republic of China to design observation tables for observation and summary. At present, various studies are under way, although the final conclusion has not yet been completed. However, from the experimental results of toxicological studies and pharmacodynamic studies that have been completed, Hepatocellular Carcinoma Powder has the following characteristics: (1) Safe and non-toxic No long-term toxicity was found in LD50>300g crude drug/Kg, large dose 50g crude drug/Kg, medium dose 30g crude drug/Kg, small dose 10g crude drug/Kg; (2) Has good anti-cancer and anti-pathogenic factors effects. It has strong killing effect on hepatocellular carcinoma, lung cancer, gastric cancer and intestinal cancer cells and has the most obvious killing effect on hepatocellular carcinoma cells (killing rate of 0.1g crude drug/ml is 100%, killing rate of 0.01g crude drug/ml is 99.05%, killing rate of 0.0001g crude drug/ml is 82.8%). It has a good effect on reducing the tumor weight of S180 and prolonging the life of animals bearing Ehrlich ascites cancer; (3) It has good effect of strengthening the body resistance that can enhance the normal immunity of animals, can improve cellular immunity and humoral immunity, can alleviate the immunosuppressive effect of chemotherapeutic drugs on animals, and improve the immunity of tumor-bearing animals; (4) It has synergistic and detoxifying effects on chemotherapeutic drugs. It is a promising new drug for the treatment of hepatocellular carcinoma.