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The Chinese University of Hong Kong (Hong Kong).

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Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases./
Author:	Wu, Ka.
Description:	324 p.
Notes:	Adviser: Leung Ping Chung.
Contained By:	Dissertation Abstracts International68-03B.
Subject:	Biophysics, Medical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3254603

Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases.
Wu, Ka.

Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases. - 324 p.

Adviser: Leung Ping Chung.

Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2006.

Malignant tumours leading to high mortality and morbidity are a serious threat to human health. It is the leading cause of death in China. In Hong Kong, there are over 20 thousand new cancer cases and more than 1100 people die due to cancers every year.Subjects--Topical Terms:

1017681
Biophysics, Medical.

Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases.
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035 $a (UMI)AAI3254603
035 $a AAI3254603
040 $a UMI $c UMI
100 1 $a Wu, Ka. $3 1023949
245 1 0 $a Clinical observation and experimental study of the efficacy of a Chinese medicine formula on malignant tumour bone metastasis diseases.
300 $a 324 p.
500 $a Adviser: Leung Ping Chung.
500 $a Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1570.
502 $a Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2006.
520 $a Malignant tumours leading to high mortality and morbidity are a serious threat to human health. It is the leading cause of death in China. In Hong Kong, there are over 20 thousand new cancer cases and more than 1100 people die due to cancers every year.
520 $a Malignant tumour is characterized by early metastasis. Among them 37 to 80 (depending on which type of cancer) patients show tendency of bone metastasis. Bone metastasis is usually accompanied by various complications, such as severe pain, pathological bone fracture, hypercalcemia, and bone marrow suppression, which can substantially affect the quality of life of the patients. Thus, the prevention and treatment of bone metastasis in cancer is an issue worth pursuing.
520 $a At present, there is no cure for bone metastasis. The current goals in patient care are to palliate pain, prevent pathological bone fracture and increase the strength and function of bone, so as to extend the life expectancy and maintain a good quality of life. Bisphosphonate treatment is the currently standard therapy of bone metastasis and is commonly used by physicians; it alleviates the tumour-induced hypercalcemia in 90% of patients and reduces the metastatic bone pain in 50% of patients. Moreover, it also prevents the pathological fracture of the affected bones. However, while effective, bisphosphonate injections are very costly, though its oral formulation is less expensive it is also less efficacious, and causes gastrointestinal discomfort. Furthermore, prolonged use of bisphosphonate treatment may lead to certain adverse effects, including hypocalcemia. These factors will prohibit the longterm use of such medication as it can negatively affect the treatment outcome.
520 $a Chinese medicine has long been used to treat cancers. Its advantages reside in its holistic properties, which bring palliative, corrective and convalescing functions against damage caused by radiotherapy, chemotherapy and surgery. These features position Chinese medicines as the adjuvant to orthodox cancer treatment. During the late stage of tumour development, when standard therapy is no longer effective, Chinese medicine plays a critical role as an integrated therapy. Searching for a safe, inexpensive and effective Chinese medicine preparation suitable for prolonged use as adjunct therapy in late cancer cases is of paramount importance.
520 $a In accordance with Chinese medicine, bone metastasis can be categorized into "bone tumour" "bone erosion" "bone wilting" "bone necrosis" and "bone impediment". The main cause of bone metastasis is twofold: cancer toxicity, and in Chinese medicine theory, the kidney governs the bone marrow, if the kidney is not functioning in balance, then the bone will become weak. Cancer toxicity is the "pathogenic cause" to skeletal metastases, while kidney weakness decreases the body defence against the cancer. A vicious cycle ensues when cancer and kidney deficiency and bone weakness occurs simultaneously coincidently and worsens the conditions.
520 $a Based on the above-described understanding of Chinese medicine and bone metastasis, supplementing the kidney and strengthening bone could be the basic principle for the treatment of bone metastasis using Chinese medicine. In view of this theory, and in addition to the clinical observation and a thorough search of the available literature, we selected relevant kidney-tonifying Chinese herbs, namely (Fructus Ligustri Lucidi), (Rhizoma Drynariae), (Herba Epimedii), (Psoralea Corylifolia) and wide-spectrum anticancer herbs (Herba Hedyotidis Diffusae) for the preparation of a combined formula--BBYNG.
520 $a Study objectives. To elucidate the efficacy and some pharmacological aspects of BBYNG in regard to the treatment of bone metastasis through clinical observation and different laboratory experiments. This study would be of significant reference value to the disease-oriented drug formulation and application, mechanistic study and research methodology of the treatment of bone metastasis using Chinese medicines.
520 $a The research study is composed of three parts, the clinical study, in vivo animal study and in vitro study on tumour cell lines. The research methods used are as follows: Clinical study . The study was designed as a randomized, parallel-group comparison between BBYNG formula and Bisphosphonate. The patients who meet the inclusion/exclusion criteria were randomly assigned to receive either BBYNG granules, which was prepared by a GMP manufacturer, or Clodronic acid. The treatment period was 6 months (24 weeks). For both groups, various clinical parameters such as body functions, blood examinations, bone density (BMD) assessment, X-ray examinations, pain intensity and quality of life were evaluated and compared.
520 $a In vivo animal study. A well-established animal model for breast cancer was used to evaluate and compare the pharmacological effects of BBYNG formula and Clodronic acid, as shown by different indicators such as tumour progression, animal's mobility, survival time, bone metastasis-induced fracture intensity and the immunological status of the tumour-bearing mice.
520 $a In vitro study on tumour cell lines. The anticancer effects of different concentrations of BBYNG formula and various single components against human breast cancer and lung cancer cell lines were evaluated by cell viability test (MTT assay), cell apoptosis test and invasion suppression test.
520 $a The clinical and laboratory experimental results are summarized as below: Clinical results. Both Chinese medicine and Western medicine treated patients showed no significant change in their blood parameters or liver and kidney examinations before and after drug administration; Male subjects on BBYNG, their bone mass density remained stable after 6 months treatment and the subjects on OSTAC showed slightly decreased In females, subjects on BBYNG remained stable, but subjects on OSTAC slightly increased.
520 $a Those on BBYNG treatment showed more a stable and satisfactory quality of life than those in the Western medicine-treated group. For the Clodronic acid treatment group, patients generally showed worsened symptoms and quality of life deteriorated. The ECOG index of the BBYNG group was statistically better than that of the Clodronic acid group. Within the 72-week clinical observational period, the mortality of Clodronic acid group is significantly higher that of the BBYNG group. The effects of BBYNG group as presented in relieving the pain-induced influence on patients' emotion, interpersonal relationship and entertainment was more pronounced than that in the Clodronic acid group.
520 $a In vivo animal study results. (Tumour growth was slower in the BBYNG treatment group when compared to the OSTAC and control groups, but this was not significantly difference) BBYNG significantly delayed tumour growth in tumour bearing mice, but it did not minimize the tumour size markedly. Moreover, BBNYG did minimize the mobility restriction caused by tumours, reduce the damage to bones, prolong the survival time and enhanced the T lymphocyte immunity.
520 $a In vitro study results. BBYNG and the aqueous extracts of its component herbs at very low drug concentrations stimulated the growth of three tumour cell lines tested. When the concentrations were slightly increased, they showed an inhibitory effect on cancer cell proliferation. As the drug concentrations further increased, the extracts showed cytotoxic effects on these tumor cells. At the noncytotoxic dose, the extracts could trigger apoptosis and enhance the caspase-3 activity in all three tumour cell lines. In addition, at this "non toxic" concentration, the extracts markedly inhibited the in vitro invasive property of the 4T1 breast cancer cell lines in our Matrigel invasion model. Thus these in vitro results suggested that BBYNG possess anticancer, invasion-inhibitory and anti-metastatic activities.
520 $a Conclusions. (1) As an adjuvant to patients with bone metastases, BBYNG is effective in relieving the metastatic bone pain, improving the quality of life. (2) In the animal model, BBYNG reduced the metastatic bone damage, prolonged the survival and enhanced the T lymphocyte immunity in the tumour-bearing mice. (3) In vitro study on the breast and lung cancer cell lines showed that BYYNG could induce apoptosis and prevent tumour cell invasion. It suggests that BYYNG may restrict tumour growth and development, thus reducing the occurrence of bone metastasis. Based on enormous medical potentials illustrated by the aforementioned findings, BBYNG deserves wider clinical application, large-scale clinical study on its preventive effect against bone metastasis and detailed investigation of its mode(s) of action in the body.
590 $a School code: 1307.
650 4 $a Biophysics, Medical. $3 1017681
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0760
690 $a 0992
710 2 $a The Chinese University of Hong Kong (Hong Kong). $3 1017547
773 0 $t Dissertation Abstracts International $g 68-03B.
790 $a 1307
790 1 0 $a Chung, Leung Ping, $e advisor
791 $a Ph.D.
792 $a 2006
793 $a Chinese
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3254603