[Tea consumption and cancer: a Mendelian randomization study].

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

[Association between tea consumption and all-cause mortality in Chinese adults].

Objective: To investigate the association between tea consumption and the risk of all-cause and cause-specific mortality among Chinese adults. Methods: This study was based on China Kadoorie Biobank (CKB). Tea consumption information was self-reported by participants at baseline. Death was mainly identified by linkage to the death registry system. Cox proportional hazard regression models estimated HR and 95%CI. Results: With a median follow-up of 11.1 years, there were 34 661 deaths in 438 443 participants. Compared with those who never drink tea, all-cause mortality HR(95%CI) were 0.89(0.86-0.91) and 0.92(0.88-0.95) for non-daily tea drinkers and daily tea drinkers, respectively. A statistically significant difference was found in the association of tea consumption and the risk of all-cause mortality between men and women(interaction P<0.05). The protective effect was mainly seen in men. Compared with those who never drink tea, daily tea drinkers had a reduced risk of death from ischemic heart disease, ischemic stroke, hemorrhagic stroke, cancer, respiration diseases and other causes of death, and the corresponding HR(95%CI) were 0.83(0.76-0.92), 0.82(0.69-0.97), 0.86(0.78-0.94), 1.03(0.97-1.09), 1.00(0.87-1.16), 0.84(0.78-0.90). Among never smokers and non-excessive drinkers, there was no statistically significant association between daily tea drinking and the risk of death from cancer. While smokers and excessive drinkers had an increased risk of death from cancer (interaction P<0.001). Conclusions: Tea consumers had reduced risks of all-cause mortality and partial cause-specific mortality, but not for the risk of death from cancer. On the contrary, daily tea drinkers with smoking habits and excessive alcohol drinking had an increased risk of death from cancer.

Research Note: Effects of polysaccharide-enriched Acanthopanax senticosus extract on growth performance, immune function, antioxidation, and ileal microbial populations in broiler chickens.

Acanthopanax senticosus (AS) is a well-known, highly effective traditional Chinese herbal medicine. Polysaccharides extracted from AS (ASPS) have multiple pharmacologic and biological activities with potential use as additives in broiler chicken feed. This trial evaluated the effects of dietary ASPS on growth performance, immune function, antioxidation, and ileal microbial populations in broiler chickens. A total of 240 1-day-old Arbor Acres male broiler chicks were randomly divided into 4 groups, with 10 replicates of 6 chicks and fed a corn- and soybean-based diet supplemented with 0, 1, 2, or 4 g/kg ASPS. Compared with the control group, supplementation with 1 g/kg ASPS increased ADG and ADFI in the finisher and overall periods and decreased the feed conversion ratio in the finisher period (both P < 0.05). Serum IgA and IgM were significantly increased by supplementation with 1 and 2 g/kg of ASPS (P < 0.05). Superoxide dismutase and glutathione peroxidase activities were increased and malondialdehyde concentration was decreased in birds fed ASPS-supplemented diets compared with those in the control group (P < 0.05). Polysaccharides extracted from AS supplementation increased Lactobacillus and decreased Escherichia coli and Salmonella counts in the ileal contents compared with the control diet (both P < 0.05). The results show that dietary ASPS improved growth performance, immune status, and antioxidant capacity and stimulated the growth of beneficial gut bacteria in broiler chickens. In conclusion, ASPS was effective as a natural additive in broiler chicken feed; 1 g/kg can be considered as the optimum dosage.

Effects of dietary Lycium barbarum polysaccharides on growth performance, digestive enzyme activities, antioxidant status, and immunity of broiler chickens.

Lycium barbarum polysaccharides (LBP) are considered to be the major bioactive components of L. barbarum and have been widely used as a well-known traditional Chinese medicine and functional food because of their various biological activities. However, no published research has investigated the use of LBP as a feed additive in broilers. The objective of this study was to evaluate the effects of dietary LBP supplementation on the growth performance, digestive enzyme activities, antioxidant status, and immunity of broiler chickens. A total of 256 one-day-old Arbor Acres male broiler chicks were randomly allotted into 4 groups, with 8 replicates of 8 birds each, and were fed a corn-soybean meal-type basal diet supplemented without (control group) or with 1,000, 2,000, or 4,000 mg/kg LBP for 6 wk. The results showed that compared with the control diet, a significant increase in ADG (P < 0.05) during the grower and overall periods was observed in chickens fed the basal diet supplemented with 2,000 mg/kg LBP, whereas supplementation with 1,000 or 2,000 mg/kg LBP decreased feed-to-gain ratio (P < 0.05) during the starter period. The inclusion of LBP in the broiler diets increased overall amylase, lipase, and protease activities (P < 0.05). Supplementation with increasing levels of dietary LBP increased the activities of superoxide dismutase and glutathione peroxidase but decreased malondialdehyde content in the serum and liver (P < 0.05). Broilers fed with LBP-containing diets exhibited higher serum IgG and IgA concentrations (P < 0.05) than the broilers fed with the control diet. Serum tumor necrosis factor α and IL-4 concentrations were significantly elevated in the group fed 2,000 mg/kg LBP compared with the control group (P < 0.05). Broilers fed diets supplemented with LBP showed linear (P < 0.05) and quadratic (P < 0.05) increases in serum IL-6 and interferon gamma concentrations. The results indicated that dietary LBP supplementation can improve growth performance, digestive enzyme activities, antioxidant capacity, and immune function of broilers. In conclusion, LBP may be used as a promising feed additive for broilers, and a supplementation level of 2,000 mg/kg LBP in the broiler diet is recommended.

Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial.

UNLABELLED: This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. INTRODUCTION: The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. METHODS: In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0 years; 49 % female) were randomized to receive either high dose (4.5 g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45 g/day) omega-3 fish oil for 2 years. BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry. RESULTS: In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm(2), respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm(2), respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95 % confidence interval (CI) -7.9 to 15.3 mg/cm(2) and femoral neck -5.5, 95 % CI -14.9 to 3.9 mg/cm(2)). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55 years at the baseline) (all P ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. CONCLUSION: A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Concern and risk perception: effects on osteoprotective behaviour.

This study aimed to determine the effect that level of concern for osteoporosis, as well as self-perceived risk of osteoporosis and fracture, has on supplementation use, seeking medical advice, bone mineral density (BMD) testing, and antiosteoporosis medication (AOM) use. Study subjects were 1,095 female Australian participants of the Global Longitudinal study of Osteoporosis in Women (GLOW) untreated for osteoporosis at baseline. Study outcomes from self-administered questionnaires included calcium and vitamin D supplementation, self-reported seeking of medical advice regarding osteoporosis, BMD testing, and AOM use in the last 12 months at the late assessment. Logistic regression was used in the analysis. Concern significantly increased the likelihood of seeking medical advice and, however, had no significant impact on screening or treatment. Heightened self-perceived risks of osteoporosis and fracture both significantly increased the likelihood of seeking medical advice and BMD testing while elevated self-perceived risk of fracture increased AOM use. Supplementation use was not significantly associated with concern levels and risk perception. Concern and risk perceptions to osteoporosis and fracture were significantly associated with certain bone-protective behaviours. However, the disconnect between perceived osteoporosis risk and AOM use illustrates the need to emphasize the connection between osteoporosis and fracture in future education programs.

Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial.

SUMMARY: Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73). INTRODUCTION: This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly. METHODS: In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months. RESULTS: Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group. CONCLUSIONS: Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China.

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Weekly gemcitabine plus 24-h infusion of high-dose 5-fluorouracil/leucovorin for locally advanced or metastatic carcinoma of the biliary tract.

Both gemcitabine and weekly 24-h infusion of high-dose 5-fluorouracil/leucovorin (HDFL) have shown promising antitumour activity for patients with locally advanced or metastatic carcinoma of the biliary tract (CBT). From April 1999 through December 2002, 30 patients with inoperable CBT were treated with gemcitabine 800 mg m(-2), intravenous infusion for 30 min, followed by 5-FU, 2000 mg m(-2) and leucovorin, 300 mg m(-2), intravenous infusion for 24 h, on day 1, 8 and 15, every 4 weeks. A total of 166 cycles were given (median of four cycles per patient, range 1-24 cycles). Response was evaluable in 28 patients and toxicity in 29 patients. Partial response was obtained in six patients, stable disease in 13, while progressive disease occurred in nine. The objective response rate was 21.4% (95% CI: 5.2-37.6%). The most common grade 3 or 4 toxicity was infection (nine patients). Other types of grade 3 or 4 toxicity included leucopenia (four patients), thrombocytopenia (three patients), anaemia (three patients), nausea/vomiting (two patients) and elevation of liver transaminases (three patients). As of 30 September 2003, the median progression-free survival was 3.7 months (95% CI: 2.8-4.6 months) and the median overall survival was 4.7 months (95% CI: 0.8-8.6 months). Our data suggest that weekly gemcitabine plus HDFL is modestly active with acceptable treatment-related toxicity for patients with advanced CBT.

Effects of hepatocyte growth-promoting factor and panax notoginseng saponins on intrasplenic hepatocellular autotransplantation.

AIM: To increase the weight of liver tissue mass present in spleen and to shorten the regeneration period of transplanted hepatocytes by stimulating DNA synthesis and protection against ischemic-reperfusion injury. METHODS: Hepatocyte growth-promoting factor (PHGF) and panax notoginseng saponins (PNGS) were used after intrasplenic hepatocellular autologous transplantation (IHAT) with 70 % partial hepatectomy. Histological examinations were carried out under both light and electron microscopy and content of ALT in hepatized spleen homogenate was investigated 2 weeks after transplantation. Furthermore, 99mTc diethyl-iminodiacetic acid (99mTc-HIDA) splenic scintiphotography was carried out and proliferation index of transplanted hepatocytes was detected by flow cytometry at the 12th week after operation. RESULTS: (1) Hepatocellular degeneration was slightly less in group B [intrasplenic hepatocyte autologous transplantation (IHAT) + PNGS 25 mg/kg, im, qd] vs the control group (group C, IHAT without drugs) at the 2nd week after transplantation, and the ALT content of group B (928 U/g +/- 268 U/g) was higher than that of group C (639 U/g +/- 138 U/g, P < 0.01). (2) At the 12th week, hepatocellular regeneration in group A (IHAT + PHGF 5 mg/kg, im, qd) was obviously better than that in group C, and the ALT content (2325 U/g +/- 401 U/g ), the radioactivity accumulation of 99mTc-HIDA (58 Bq +/- 18 Bq), and proliferation index (3.8 % +/- 0.4 %) of group A were all higher than those of control (P < 0.05). CONCLUSION: PHGF has effects in increasing the weight of liver tissue grown in spleen and shortening the regeneration period of the transplanted hepatocytes, while PNGS has certain effects on protecting the hepatocytes against ischemic reperfusion injury in the early stage of transplantation.

In vitro effect of hyperbaric oxygen on the chemolysis of infective stones.

BACKGROUND: In order to extend the feasibility of hyperbaric oxygen therapy in the urological field, the present study aimed to investigate the dissolution activity of human infective stones in UROCITRA solution under hyperbaric oxygen condition. METHODS: The dissolution activity of 7 struvite and 11 mixed struvite and carbonate apatite stones in UROCITRA solution were studied under 2.5 atmosphere (atm) hyperbaric oxygen (HBO) status in a Sigma I N-124 monoplace chamber. Another 7 struvite and 10 mixed struvite and carbonate apatite stones were also studied under normal condition. Chemolysis was performed in a drip device with a 150-ml/hour continuous flow rate. RESULTS: Under 2.5 atm HBO status, the PO2 of UROCITRA solution was 365 +/- 44 mmHg, which was significantly higher than that of tap water (113 +/- 62 mmHg) and UROCITRA solution (125 +/- 12 mmHg) under normobaric condition (p < 0.001). The decreases in the stone weight of struvite under normobaric condition were 31 +/- 8.8% after 2 h and 48 +/- 15% after 4 h of treatment. The HBO-enriched UROCITRA solution did not increase the dissolution activity as reflected by comparable decreases in the dried stone weight (31.2 +/- 14.6% and 54 +/- 19% at the 2nd and 4th post-treatment hours, respectively, p > 0.05). Similarly, there was no significant difference in the percent stone weight decrease of the mixed struvite and carbonate apatite stones under either HBO or normobaric condition. The dissolution responsiveness of struvite was significantly greater than that of the mixed struvite and carbonate apatite stones. CONCLUSIONS: The chemolysis of struvite in UROCITRA solution is significantly greater than that of the mixed struvite and carbonate apatite stones. However, the UROCITRA solution enriched with HBO does not enhance the dissolution of infective stones.

Intra-arterial plus i.v. chemotherapy for advanced bulky squamous cell carcinoma of the buccal mucosa.

From July 1994 to December 1996, 41 patients with previously untreated, advanced bulky squamous cell carcinoma arising from the buccal mucosa (BSCC) were enrolled. All patients were males with a median age of 47 years (range 29-72). The tumor extent was stage III/IV: three of 38, T4: 85%, N2-3: 20%. Patients were initially scheduled to receive intra-arterial (i.a.) chemotherapy, followed by i.v. chemotherapy and regional therapy. The i.a. chemotherapy catheter was properly placed by external carotid artery angiography via the femoral artery. The i.a. chemotherapy consisted of cisplatin (P) 100 mg/m(2) day 1 plus 5-fluorouracil (F) 1000 mg/m(2) day 1-4, and the i.v. chemotherapy consisted of PF (10 patients) or PF plus methotrexate 200 mg/m(2) day 15 and 22 (31 patients). All chemotherapy regimens were administered at 4-week intervals. The response rate of i.a. plus i.v. chemotherapy for the primary site was 85% (35 of 41) with 29% complete remission (CR) (12 of 41). The response and CR rates of neck nodes were 82% (14 of 17) and 41% (seven of 17), respectively. The combined overall response rate was 80% (33 of 41) with a 29% CR (12 of 41). Major toxicity from i.a. chemotherapy of WHO grade > or = 3 included: mucositis of infusion area (76%), hemialopecia (56%) and leukopenia (5%). Three neurologic complications of i.a. chemotherapy including one hemiparesis occurred. The median follow-up time was 47 months (range 36-66 months), and the overall survival and disease-free survival were both 34% (14 of 41). Four patients were cured with chemotherapy alone and eight patients (19.5%) were cured without surgical intervention. Using i.a. chemotherapy as a cytoreductive therapy followed by subsequent i.v. chemotherapy produces a high response rate and an encouraging degree of complete response rate in advanced bulky BSCC. However, toxicity management and catheter placement will need to be improved in order to better define the role of this therapy in advanced BSCC.

Mitomycin C with weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract and periampullar carcinomas.

We have reported a 33% partial response rate with acceptable toxicity using weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in patients with far advanced biliary tract cancers (BTC). In this study, we added mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and survival. From July 1997 to September 1999, 25 chemotherapy-naive patients with pathology-proven far advanced BTC and periampullar cancers were enrolled. The regimen consisted of MMC 10 mg/m(2) every 8 weeks combined with 5-FU 2600 mg/m(2) and LV 150 mg at a schedule of 24-h infusion weekly for 6 weeks followed by a 2 week break. There were 10 males and 15 females with a median age of 57 years (range 40-76). The sites of primary tumor were 15 intrahepatic cholangiocarcinomas (CC), one perihilar CCs, three distal BTC, three gallbladder cancers (GB) and three periampullar cancers. A total of 148 sessions of chemotherapy were given with a mean of 8 (range 2-18). Nineteen patients were evaluable for response. The response rate was: 26% (five of 19) partial response, 42% (eight of 19) stable disease and 32% (six of 19) progressive disease. All of the patients were evaluable for toxicity. Toxicities more than grade III-IV were thrombocytopenia 16% (four of 25), leukopenia 12% (three of 25) and vomiting 4% (one of 25). There were four treatment-related deaths. The median time to disease progression was 3 months. The median survival was 6 months. A combination of MMC with weekly high-dose 5-FU and LV in patients with BTC did not improve the response rate, but produced more toxicity than weekly high-dose 5-FU and LV alone.

Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia.

To identify new markers of minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL), gene expression of leukemic cells obtained from 4 patients with newly diagnosed ALL was compared with that of normal CD19(+)CD10(+) B-cell progenitors obtained from 2 healthy donors. By cDNA array analysis, 334 of 4132 genes studied were expressed 1.5- to 5.8-fold higher in leukemic cells relative to both normal samples; 238 of these genes were also overexpressed in the leukemic cell line RS4;11. Nine genes were selected among the 274 overexpressed in at least 2 leukemic samples, and expression of the encoded proteins was measured by flow cytometry. Two proteins (caldesmon and myeloid nuclear differentiation antigen) were only weakly expressed in leukemic cells despite strong hybridization signals in the array. By contrast, 7 proteins (CD58, creatine kinase B, ninjurin1, Ref1, calpastatin, HDJ-2, and annexin VI) were expressed in B-lineage ALL cells at higher levels than in normal CD19(+)CD10(+) B-cell progenitors (P <.05 in all comparisons). CD58 was chosen for further analysis because of its abundant and prevalent overexpression. An anti-CD58 antibody identified residual leukemic cells (0.01% to 1.13%; median, 0.03%) in 9 of 104 bone marrow samples from children with ALL in clinical remission. MRD estimates by CD58 staining correlated well with those of polymerase chain reaction amplification of immunoglobulin genes. These results indicate that studies of gene expression with cDNA arrays can aid the discovery of leukemia markers. (Blood. 2001;97:2115-2120)

Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer.

BACKGROUND: A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. PATIENTS AND METHODS: From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. RESULTS: There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. CONCLUSIONS: This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

[Effect of tuoli xiaodu powder on cell-mediated immunofunction in liver carcinoma patients before and after surgical operation].

OBJECTIVE: To explore the regulatory effect of Tuoli Xiaodu Powder (TLXDP) on cell mediated immunofunction (T-lymphocytes subsets) in liver carcinoma patients. METHODS: Thirty-eight patients with operable liver carcinoma were divided randomly into 2 groups. TLXDP was given to the 20 cases in Group I before and 7 days after surgical operation, but not given to the 18 cases in Group II. T-lymphocyte subsets (CD3, CD4 and CD8 by monoclonal antibody labelled direct immune rosette method) and liver function, aspartate aminotransferase (AST), alanine transaminase (ALT), direct and indirect bilirubin (DBIL and IBIL) were determined before and after treatment. RESULTS: T-lymphocyte subsets elevated and liver function enhanced significantly in Group I after treatment, but unchanged in Group II. CONCLUSION: Administration of TLXDP before and after surgical operation could enhance the cell-mediated immunofunction and improve the liver function significantly in patients with liver carcinoma.

Estrogenic Effects of Cimicifuga racemosa (Black Cohosh) in Mice and on Estrogen Receptors in MCF-7 Cells.

The estrogenic effects of Cimicifuga racemosa or Actacea racemosa (black cohosh, CR) extracts were tested in mice, and their effects on estrogen receptor (ER) levels in human breast cancer MCF-7 cells were also investigated. Four groups of weanling female Kunming mice were given 0 (control), 75, 150, or 300 mg/kg body weight CR extracts orally for 14 days. The estrus cycle and the weights of the uterus and ovary of mice, as well as serum estradiol (E(2)) were measured. The proliferation patterns of MCF-7 cells exposed to CR extracts or 17beta-estradiol were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, growth of MCF-7 cells in 0 (control) or 4.75 &mgr;g/L of CR extracts or 0.3 nmol/L of 17beta-estradiol groups were observed for 5 days. ER levels in MCF-7 cells were analyzed by indirect immunofluorescence assay using flow cytometry. The uterine weights of mice increased with the increase in dosage of CR extracts, and the estrus duration was significantly prolonged in the group receiving 300 mg/kg body weight (P <.05). However, CR extracts did not increase the serum E(2) concentration significantly. In the in vitro study, a dose-response relationship was demonstrated when cells were treated with low doses of CR extracts, and the optimal enhancement concentration of CR extracts was 4.75 &mgr;g/L on MCF-7 cells. The doubling times (T(D)) of cell growth in the CR extracts group and the 17beta-estradiol group were 32.1 and 31.7 hours, respectively, both shorter than that of the negative control group (T(D) = 35.3 hours). Additionally, 4.75 &mgr;g/L of CR extracts resulted in significantly increased ER levels compared with the control group (P <.01). In conclusion, CR extracts produced an estrogenic action. The effect of increasing ER levels by CR extracts may be one of the potential mechanisms of its phytotherapeutic effects for postmenopausal symptoms.

Severe reversible bone marrow suppression induced by Selaginella doederleinii.

CASE REPORT: We report a 52-year-old female patient with cholangiocarcinoma who developed severe bone marrow suppression after taking Selaginella doederleinii as an alternative anticancer treatment. She developed severe pancytopenia with initial presentations of skin ecchymosis, itching, and gum bleeding 2 weeks after taking Selaginella doederleinii daily. Bone marrow smear and biopsy showed severe hypocellularity with no malignant cell infiltration. Approximately 1 week after stopping Selaginella doederleinii, her hemogram returned to previous levels. Selaginella doederleinii, a popular anticancer herb, may contain an as yet unidentified substance that contributes to reversible bone marrow suppression.