Challenges to effective cancer control in China, India, and Russia.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

Acceptable cardiac safety profile of neoadjuvant 5-fluorouracil, epirubicin, cyclophosphamide and celecoxib (FEC-C) for breast cancer: a subanalysis of biomarkers for cardiac injury.

PURPOSES: This substudy aimed to examine the changes in biomarkers for cardiac injury in patients who received neoadjuvant 5-fluorouracil, epirubicin, cyclophosphamide with concurrent celecoxib (FEC-C). METHODS: Thirty-four female patients with histologically confirmed locally advanced breast cancer preoperatively received 3 cycles of FEC-C (500 mg/m2, 75 mg/m2, 500 mg/m2) with concurrent celecoxib (400 mg bid). Blood samples were drawn from patients on day (D) 0, D3, D21, D42, and D63 (end of therapy), and the serum levels of lactate dehydrogenase (LDH) and plasma levels of cardiac troponin I (cTnI) and N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) were measured with commercially available test kits. RESULTS: All patients tolerated this regimen well. Neither life-threatening toxicity nor clinical symptoms of cardiac damage were observed. Serum LDH increased significantly from baseline after 3 cycles of FEC-C (p<0.0001), but the change was possibly brought about by chemotherapy-induced liver derangement. However, NT-proBNP decreased significantly (p=0.009), while cTnI increased nonsignificantly (p=0.078) after 3 cycles of FEC-C compared to baseline, although this increase was still regarded as normal. CONCLUSIONS: Short-term use of the FEC-C regimen has proven to be effective in locally advanced breast cancer, with an acceptable cardiac safety profile.

Using association rules mining to explore pattern of Chinese medicinal formulae (prescription) in treating and preventing breast cancer recurrence and metastasis.

BACKGROUND: Chinese herbal medicine is increasingly widely used as a complementary approach for control of breast cancer recurrence and metastasis. In this paper, we examined the implicit prescription patterns behind the Chinese medicinal formulae, so as to explore the Chinese medicinal compatibility patterns or rules in the treatment or control of breast cancer recurrence and metastasis. METHODS: This study was based on the herbs recorded in Pharmacopoeia of the People's Republic of China, and the literature sources from Chinese Journal Net and China Master Dissertations Full-text Database (1990 - 2010) to analyze the compatibility rule of the prescription. Each Chinese herb was listed according to the selected medicinal formulae and the added information was organized to establish a database. The frequency and the association rules of the prescription patterns were analyzed using the SPSS Clenmentine Data Mining System. An initial statistical analysis was carried out to categorize the herbs according to their medicinal types and dosage, natures, flavors, channel tropism, and functions. Based on the categorization, the frequencies of occurrence were computed. RESULTS: The main prescriptive features from the selected formulae of the mining data are: (1) warm or cold herbs in the Five Properties category; sweet or bitter herbs in the Five Flavors category and with affinity to the liver meridian are the most frequently prescribed in the 96 medicinal formulae; (2) herbs with tonifying and replenishing, blood-activating and stasis-resolving, spleen-strengthening and dampness-resolving or heat-clearing and detoxicating functions that are frequently prescribed; (3) herbs with blood-tonifying, yin-tonifying, spleen-strengthening and dampness-resolving, heat-clearing and detoxicating, and blood-activating with stasis-resolving functions that are interrelated and prescribed in combination with qi-tonifying herbs. CONCLUSIONS: The results indicate that there is a close relationship between recurrence and metastasis of breast cancer with liver dysfunctions. These prescriptions focus on the herbs for nourishing the yin-blood, and emolliating and regulating the liver which seems to be the key element in the treatment process. Meanwhile, the use of qi-tonifying and spleen-strengthening herbs also forms the basis of prescription patterns.

Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance.In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray. METHODS: Siliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use.The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy.A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline). RESULTS: After 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation.On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001). CONCLUSIONS: In this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies.

Effect of Sanguisorba officinalis L on breast cancer growth and angiogenesis.

OBJECTIVE: Sanguisorba officinalis L. (SA) has shown anti-inflammation, hematopoiesis and immunity enhancing properties. No detailed studies have been reported on its anti-cancer effects. This study therefore was undertaken to analyze its effects on human breast cancer utilizing in vitro and in vivo methodologies. METHODS: Human breast cancer cell lines MCF-7 and MDA-MB-231 were utilized for evaluating SA influences on tumor progression and angiogenesis processes like proliferation, the cell cycle, apoptosis, tube formation and migration abilities. Both cancer xenografts were also used to determine the herb efficacy in vivo. Bioactivity-guided fractionation was carried out to determine the bioactive compounds in SA. RESULTS: SA inhibited proliferation, induced S phase arrest and triggered mitochondrial pathway apoptosis in both cancer cells. Angiogenesis experiments revealed that SA inhibited VEGF expression in both cancer cell lines. Meanwhile, the proliferation, tube formation and migration abilities of endothelial cells were also inhibited. In vivo experiments demonstrated that SA reduced tumor size and neoangiogenesis in both cancer xenografts. Gallic acid and ellagic acid were finally identified as bioactive compounds in SA. CONCLUSIONS: SA might be of value as a breast cancer preventive and therapeutic agent by inducing apoptosis and inhibiting angiogenesis. Further research is needed to evaluate its metabolism and synergistic effects with chemotherapeutic drugs.

Rhodiola algida improves chemotherapy-induced oral mucositis in breast cancer patients.

OBJECTIVE: Oral ulcerative mucositis, a common adverse effect due to mainstream cytotoxic drugs, limits the nutritional intake of cancer patients. Rhodiola algida is widely used in traditional Chinese medicine to stimulate the immune system. The aim of this study is to investigate the effect of this herbal extract on healthy human lymphocytes in vitro, the homeostasis of cancer patients and the healing time of oral ulcers. METHOD: The constituents of Rhodiola algida were analyzed by RP-HPLC. Lymphocytes isolated from 462 healthy subjects were treated with 100 ug/ml Rhodiola algida for 48 h. The activity of the cells was measured by cell proliferation reagent and ATP assay. The level of various cytokines and mRNA content of lymphocytes were determined. Rhodiola algida demonstrated no toxicity in animals, which had been orally fed with 1 mg/ml Rhodiola algida for 30 days. 130 breast cancer patients from Huaxi Hospital of Sichuan University were recruited between 2006 and 2007. They received four cycles of 5-fluorouracil, epirubicin and cyclophosphamide after modified total mastectomy. These patients were randomly assigned to test and control groups. Rhodiola algida mixture was consumed by the test group for 14 consecutive days after each cycle of chemotherapy. All patients were given 0.2% chlorohexidine mouth wash to be used every day. Complete blood counts, liver and renal function tests together with the number and size of oral ulcerations were analyzed after each cycle. Weight loss, complaints of nausea or vomiting and degree of pain were noted. RESULTS: The optimal concentration of Rhodiola algida favored the proliferation of lymphocytes. The levels of IL-2, IL-4, granulocyte-macrophage colony-stimulating factor and the mRNA content of these cytokines were also enhanced. White blood cell (WBC) levels returned to normal range in both groups 1 week after every cycle of chemotherapy. WBC count increased faster in patients using Rhodiola algida; they presented with smaller and fewer oral ulcers. There were no liver or renal complications observed in any patients. CONCLUSION: Rhodiola algida increases immunity of patients who are receiving chemotherapy post mastectomy and decreases the quantity of oral ulcers. Thus Rhodiola algida has the potential to be used concurrently with chemotherapy to alleviate the occurrence of oral ulcers.

Effects of Shugansanjie Tang on matrix metalloproteinases 1, 3 and 9 and telomerase reverse transcriptase expression in human breast cells in vitro.

BACKGROUND: The traditional Chinese medication Shugansanjie Tang (SGT), whose active component is Akebia Trifoliate Koidz, possesses potential anti-tumor and immunostimulatory effects especially for breast cancer. The invasive processes of such cancers have been attributed to matrix metalloproteinases (MMPs) which may be the key factor mediating this process. Telomerase reverse transcriptase (TERT) catalyze the lengthening of telomeres, which prolongs cell life and interrupts natural cell death. The aim of this study is to determine the effects of Shugansanjie Tang on MMP levels and TERT activity using breast cancer cell lines. MATERIALS AND METHODS: We used the breast cancer cell lines MDA-MB-231 and BT-483. Cell inhibition rate was measured by WST-1 reagent, cell apoptosis by Apoptotic DNA Ladder Kit, mRNA expression of MMP-1, MMP-3 and MMP-9 by PCR and TERT by immunohistochemistry stain. RESULTS: Comparing to the control group, the test group showed lower cell growth rate, decreased mRNA expression of MMP-1, MMP-3 and MMP-9 production and less intense staining of MMPs with diaminobenzidine tetrahydrochloride. CONCLUSION: This study demonstrated that Shugansanjie Tang inhibits the growth of breast cancer cells by apoptosis and lowers the level of certain matrix metalloproteinases and activity of telomerase reverse transcriptase in breast cancer in vitro.

Neoadjuvant chemotherapy for breast cancer determined by chemosensitivity assay achieves better tumor response.

BACKGROUND: Neoadjuvant chemotherapy can potentially reduce tumor size and help downstage the tumor before definitive operation was performed. However, it was not possible to tell whether the patient would respond to the regimen until given. This difficulty can be overcome by testing the susceptibility of a sample of cancer cells in vitro: a "patient-tailored approach". In this pilot study, we attempt to demonstrate an improved response by this "patient-tailored" approach over standard regimen. MATERIALS AND METHODS: The study included 36 women with moderately advanced local breast cancer larger than 2 cm in diameter. Twelve were allocated to receive a standard regimen of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) preoperatively as controls, and 24 were given the most suitable regimen according to testing; the options were FEC, cyclophosphamide, methotrexate and 5-fluorouracil (CMF), 5-fluorouracil, adriamycin and mitomycin C (FAM) and paclitaxel alone. The cell activities of drug-treated solid tumors were compared to controls with a highly sensitive ATP bioluminescence assay. Patients received chemotherapy according to sensitivity results and the tumor area clinically measured before and after chemotherapy. RESULTS: Sensitivity-directed treatment helped patients achieve a higher rate of complete clinical response (10/24 vs. 0/12), larger mean reduction in tumor area (75% vs. 26%), and 25% pathological complete response (pCR). The paclitaxel subgroup achieved 80% (pCR). CONCLUSION: It is a useful in vitro assay to provide a reference of the particular patient who received treatment according to her sensitivity result. It may improve pathologic complete response, clinical tumor response and lead to less extensive surgery.

Fructus Schisandrae (Wuweizi) containing compound in modulating human lymphatic system - a Phase I minimization clinical trial.

BACKGROUND: Hepatitis B virus (HBV) infection afflicts Asia population and, in Hong Kong, about 10% was Hepatitis B surface antigen carrier. It is still one of the major issues under investigation. Herbal medicine KY88 composed of Fructus Schisandrae possessing immunomodulatory property was adopted by Chinese medicine practitioner for treatment of acute and chronic HBV infection. However, the underlying impact on host immune system is not fully understood. MATERIALS AND METHODS: Twenty-three healthy volunteers infected with HBV were taken peripheral venous blood from which the blood cells involved in simple host immunity was obtained. RESULTS: It was found that the circulating monocyte count significantly drop after 2weeks of KY88 therapy whereas the fall did not return back to baseline. Circulating white blood cell, neutrophil and lymphocyte, however, did not show obvious change upon commencement of KY88 therapy. CONCLUSION: It was postulated that reduction in circulating monocyte count may reduce the self-inflicted host immune injury to hepatocyte which may testify the hepatoprotective ability of the herb. But, the exact mechanism on how immunomodulatory properties of the herbal medicine protect chronic HBV carriers from liver injury remains a myth.

The inhibitory effect of a herbal formula comprising ginseng and carthamus tinctorius on breast cancer.

A compound (Zhu-xiang) from herbal extracts containing ginseng and carthamus tinctorius was used to treat the MDA-MB-231 breast cancer cell and normal human mammary gland cell lines. The inhibition of cell proliferation by Zhu-xiang, epirubicin, 5-fluorouracil and cyclophosphamide was determined by WST-1 assays. The apoptotic effect was studied by flow cytometry analysis of DNA strand breaks and ApopTag Peroxidase In Situ Apoptosis kit by the TUNEL assay. The proliferation index as well as cell cycle progression were also evaluated by flow cytometry using Ki-67 and propidium iodide respectively as markers. The Zhu-xiang showed significantly inhibition in cell proliferation and the inhibition was dose dependent. The inhibitory effect of Zhu-xiang was significantly greater than commonly used cytotoxic drugs. The inhibitory effect is a result of the induction of apoptosis, which is concentration- and time-dependent. DNA histograms indicate that the compound causes accumulation of cells mainly in the S phase. The viability of cells in breast solid tumours was measured by ATP bioluminescence assay to determine the drug-induced cytotoxicity of Zhu-xiang. The three different concentrations of Zhu-xiang all exhibited the ability to inhibit proliferation in solid tumour. Zhu-xiang could be a useful anti-cancer compound against breast cancer.

Radix bupleuri containing compound (KY88 liver-livo) induces apoptosis and production of interleukin-4 and tumor necrosis factor-alpha in liver cancer cells in vitro.

Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50 and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-alpha. However, significant changes were observed only for IL-4 and TNF-alpha. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-alpha.

Pattern of alternative medicine usage among the Chinese breast cancer patients: implication for service integration.

The study examined the pattern of and factors associated with use of alternative medicine (AM) among Chinese breast cancer patients. An analytical, cross-sectional survey of 352 breast cancer patients from two breast cancer centers was conducted in 1997. Amongst the respondents, the usage rate of alternative medicine was 27.8%. Factors forming the use of AM included being young to middle-aged, having higher education and a belief that AM would enhance orthodox treatment. A substantial proportion of Chinese breast cancer patients use AM besides conventional medicine. There is a need to integrate AM with conventional medicine to improve the service provision for cancer patients.

Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and down-regulating cyclin D1 gene.

The use of herbal medicine is a common practice among Chinese women with breast cancer. Yunzhi (Voriolus versicolor), a substance that is regarded as a biological response modifier, is frequently used. The aim of the present study is to evaluate the anti-proliferative action of, Yunzhi, polysaccharide peptide (PSP), on breast cancer cells. Breast cancer cells (MDA-MB-231) were cultured with and without PSP for 7 days. Cell growth at 24, 72, 120 and 168 hours was measured by Cell Proliferation Reagent (WST-1). Cells treated with PSP were found to have a significant reduction in cell proliferation as compared to controls after 72 hours of incubation. This lasted for 168 hours. When the effect of PSP on apoptosis was studied by the TdT-mediated X-dUTP nick end-labeling (TUNEL) assay, we found that PSP had a significant effect upon apoptosis from 24 hours onward. Immunostaining showed that PSP increased p21 expression and decreased cyclin D1 expression. In conclusion, PSP is effective in inhibiting cell proliferation through apoptosis. The mechanism for the apoptosis may be through up-regulation of p21 and down-regulation of cyclin D1.