Experimental and Clinical Research on YWKL for Late Stage Gastric Carcinoma

Dr. Jinmei Tian

China Academy of Chinese Medical Science

1995-1998

[Objectives]

To study the hematological and immunological changes of the organism inthe process of the occurrence and development of gastric carcinoma; Observe theclinical treatment effect of YangWeiKangLiu Powder (YWKL; an herbal medicine;Composition: Radix Astragali seu Hedysari, Radix Ginseng, Rhizoma AtractylodisMacrocephalae, Radix Notoginseng, Radix Paeoniae Rubra, Lignum Sappen.) and itsanti-cancer and anti-metastasis effects on mice bearing tumor; To inquire intothe relationship between the treatment effect of YWKL and its influence on thehematological and immunological changes of the organism bearing tumor; Todiscuss the rational application of the PBCRBS method (promoting bloodcirculation and removing blood stasis) in the treatment of cancer; To comparethe treatment effects of the integrative therapy (chemotherapy plus YWKL) andthe pure chemotherapy.

[Methods]

The research had three parts ¾ literatureresearch, clinical research and experimental research.

The clinical research was designed as a prospective study and themethods of randomization, control, blind and quantification were applied. Theclinical treatment effect was comprehensively evaluated. The blood rheologytechnology and the clinical examination methods on blood coagulation andfibrinolysis were used for observing the hematological changes in the patients.

In the experimental research, the animal models of the micefore-stomach carcinoma (FC) and the mice sarcoma 180 (S₁₈₀) wereused. The anti-cancer and anti-metastasis effects were observed by pathologicalmethods. The hematological and immunological changes in the mice bearing tumorand the effect of the treatments on the changes were studied by thehematological methods, immunological methods and the flow cytometry (FCM)technology. Divide YWKL into two parts ¾ invigorating-qi herbs (i.e.Radix Astragali seu Hedysari, Radix Ginseng, Rhizoma AtractylodisMacrocephalae) and promoting-blood-circulation herbs (i.e. Radix Notoginseng,Radix Paeoniae Rubra, Lignum Sappen); Observe respectively the effects ofinvigorating-qi herbs and promoting-blood-circulation herbs on the hematologicaland immunological changes in the mice bearing tumor (FC) so as to inquire intothe significance of the application of complex prescription in the treatment ofcancer.

[Results]

CLINICAL RESEARCH

1.   The integrative therapy was significantly betterthan the pure chemotherapy at improving the symptoms and the quality of life;YWKL can reduce the side effects of the chemotherapy so that it can help thepatients accomplishing the treatment course; in controlling the size of thecancer focus and the distance metastasis, the integrative therapy also showedits superiority.

2.   The patients with late gastric carcinoma were in thehypercoagulable state ¾ the whole bloodviscosity (WBV), the RBC aggregation (RBCA) and PLT aggregation (PLTA)significantly increased and the increasing of the platelet aggregation was themost significant. But the RBC deformation (RBCD) did not show apparent change.

3.   The positive rate of D-dimer in patients with lategastric carcinoma was 44%. It indicated that the thrombogenesis was ofuniversality in patients with late gastric carcinoma (Stage IIIb & IV),that is, the patients having distance metastasis or going to have distancemetastasis. The thrombogenesis was in close relationship with cancermetastasis.

4.   The incidence rate of Activated Protein C Resistance(APCR) was high (20%) in patients with late gastric carcinoma. APCR wasprobably one of the key reasons for the prethrombotic state of the patients.The relationship of its incidence mechanism and the development of cancer wasworthy of further research.

5.   The pure chemotherapy aggravated the hypercoagulablestate of patients with late gastric carcinoma, showing that the WBV, the RBCAand the PLTA did not decrease but the RBCD significantly decreased afterchemotherapy. On the contrary, the integrative therapy can significantlyimprove the hypercoagulable state of the patients. This perhaps was one of thereasons for the better treatment effects of the integrative therapy. It alsoprovided some hematological evidences for the increasing-efficacy anddecreasing-toxicity effects of the herbal medicine on the chemotherapy.

EXPERIMENTAL RESEARCH

1.  The anti-cancer (S₁₈₀) rates of YWKL, CTX(Cyclophosphamide) and YWKL+CTX were respectively 35.5%, 70.2%, 74.3%; On the 7^thday after FC transplantation, the anti-cancer rates of YWKL, CTX, YWKL+CTX,invigorating-qi herbs (IQDs) and promoting-blood-circulation herbs (PBCDs) were37.4%, 63.2%, 76.8%, 19.4%, 13.5%; On the 13^th day after FCtransplantation, they were 31.3%, 65.5%, 76.1%, 8.3%, 7.1%.

2.  YWKL, CTX, YWKL+CTX had some inhibiting effects onlocal infiltration and lung-met of FC, but the IQDs and PBCDs did not show sucheffects. The lung-met inhibiting rates were respectively 37.5%, 75%, 87.5%,12.5%, 12.5%.

3.  At the early and late stages of FC metastasis, thehematological changes in mice differed. At the early stage, the mice were inthe hypercoagulable state, the thrombogenesis already occurred and thefibrinolytic system had been activated and in a hyperfunction state. It showedthat the WBV, RBCA, PLTA, fibrinogen and D-dimer significantly increased. Atthe late stage, the mice bearing tumor were in the hyperfibrinolytic andhypocoagulable state. It showed that the WBV, RBCA, PLTA and fibrinogendecreased significantly while the D-dimer increased progressively.

4.  YWKL had comprehensive influence on the hematologicalchanges in mice bearing tumor while the IQDs and PBCDs can only improve theabnormality at some stages or in some aspects. And, at the late stage ofmetastasis, the PBCDs aggravated the hyperfibrinolytic state of the micebearing tumor to some extent.

5.  CTX aggravated the hypercoagulable state of the micebearing tumor while YWKL can correct it to some extent.

6.  In the development of cancer (FC), the CD₈⁺Tcell of the mice bearing tumor decreased significantly. Based on the lateliterature, the decrease of CD₈⁺T cell does not mean thedecrease of T suppressor, it means the decrease of T-cell immune function.

7.  YWKL had some regulatory effects on the cellularimmune function of the mice bearing tumor (FC). It can significantly increasethe CD₈⁺T cell and to some extent, increase the CD₄⁺Tcell and NK cell. The PBCDs showed the immunosuppressive effect (CD₈⁺Tcell significantly decreased.) while the IQDs can correct it to some extent.

[Conclusions]

1.    In the process of the development of gastriccarcinoma, the hematological changes in the organism are complicated. It is notthe simple hypercoagulable state, but the dynamic and multi-respect disturbanceof the coagulable and fibrinolytic system.

2.    In the process of the development of gastriccarcinoma, the cellular immune function significantly decreased.

3.    The treatment effect of the integrative therapy isbetter than that of the pure chemotherapy. The mechanism is probably that YWKLcan improve the hematological and immunological changes in the organism bearingtumor to some extent.

4.    The prudent policy should be adopted when using thePBCRBS method to treat cancer. Properly combining with the IQDs will be inaccordance with the treatment theory of Traditional Chinese Medicine.

Key words:

GastricCarcinoma; Hematology; Immunology; Traditional Chinese Medicine