Effect of simulated microgravity on the photopic negative response of flash electroretinogram in adult mice / 中华眼底病杂志

Objective To observe the effect of simulated microgravity on the photopic negative response (PhNR) of full-field flash ERG in adult mice.Methods In an experimental study,forty-eight adult male C57BL/6J mice (48 eyes) were randomly divided into model and control groups.Model mice were further divided into three subgroups of 8 each:tail-suspended for 15 days (subgroup A),tail-suspended for 30 days (subgroup B),and tail-suspended for 30 days followed by returning to normal position for 30 days (subgroup C).The three control subgroups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15,30,and 60 days.The mice were immediately examined using ERG-PhNR,flash VEP,OCT and visually-guided behavior in vivo,and subsequently sacrificed to analyze the retinal histology in vitro.PhNR amplitude was measured from baseline to PhNR trough.N1 peak-time and N1-P1 amplitude of VEP was analyzed.The escape duration was used to quantitatively evaluate the visual function of mice.In addition,inner retinal thickness was analyzed by OCT imaging.Data were compared by the independent sample t-test.Results PhNR amplitude in the model subgroup A was obviously lower than the corresponding control subgroup,the difference was statistically significant (t=-3.196,P＜0.01).There was no significant difference in PhNR amplitude between the model subgroup B or C and the corresponding control subgroup (t=-1.976,0.285;P＞0.05).There was no significant difference in FVEP N1 peak-time or N1-P1 amplitude between any of the three model subgroups and the corresponding control subgroup (P＞0.05).There was no significant difference in OCT-measured inner retinal thickness between any of the three model subgroups and the corresponding control subgroup (t=-0.461,2.073,-0.402;P＞0.05).The three model subgroups showed almost normal retinal structure,including the retinal ganglion cell,inner pexiform layer,inner nuclear layer,outer plexiform layer,outer nuclear layer,ellipsoid zone and RPE.There was no significant difference in visually-guided escape time between any of the three model subgroups and the corresponding control subgroup (t=-0.637,-0.955,1.297;P＞0.05).Conclusion Via tail-suspension,short-term simulated microgravity can affect the PhNR of flash ERG;however,the change is reversible and does not affect visual function of mice.

Expression of transcriptional coactivator with PDZ-binding motif (TAZ) in colon cancer tissues and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of transcriptional coactivator with PDZ-binding motif(TAZ) in colon cancer tissues and its association with clinicopathological parameters and prognosis of patients.</p><p><b>METHODS</b>The expression of TAZ protein was detected in 56 resected colon cancer tissues and matched tumor-adjacent tissues using immunohistochemistry. The positive expression rate of TAZ was compared between patients with different clinicopathological features. The association between TAZ expression and prognosis was analyzed.</p><p><b>RESULTS</b>Expression of TAZ protein located in the nucleolus. The positive expression rate of TAZ in colon cancer tissues was significantly higher than that in matched tumor-adjacent tissues(73.2% vs. 12.5%, P=0.000). Clinicopathological evaluation suggested that the expression of TAZ protein was associated with tumor size(P=0.009), depth of infiltration(P=0.026), lymph node metastasis (P=0.007) and TNM staging(P=0.004). Colon cancer patients with negative expression of TAZ showed a better 5-year survival as compared with those with positive expression of TAZ (66.7% vs. 22.9%, P=0.0017). Multivariate Cox regression analysis revealed that positive TAZ expression was an independent factor for predicting poor prognosis in colon cancer (HR:3.532, 95% CI: 1.3-9.9, P=0.016).</p><p><b>CONCLUSION</b>The expression of TAZ protein is up-regulated in colon cancer tissues and its high expression is associated with poor prognosis of colon cancer patients.</p>

Expression of miR-146a in colon cancer and its significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate miR-146a expression in colonic cancer and its clinical implications.</p><p><b>METHODS</b>Quantitative real-time PCR was employed to detect the levels of miR-146a expression in colonic cancer tissues, pair-matched adjacent normal tissues and different colonic cancer cell lines. MTT essay was used to evaluate the proliferation of colonic cancer SW260 cells transfected with miR-146a mimics, and the cell cycle and apoptosis of the cells were analyzed with flow cytometry.</p><p><b>RESULTS</b>Compared with the normal tissues, 38 of the 43 colonic cancer samples showed down-regulated miR-146a expression, which was associated with poor tumor differentiation. The expression of miR-146a in the tumor tissues was significantly correlated with tumor size and clinical stages. The patients with high miR-146a expression levels had significantly longer total survival time than those with low expression of miR-146a. In SW260 cell cultures, transfection with miR-146a mimics significantly inhibited cell growth (P<0.05) and increased the cell apoptosis rate (11.9% vs 5.9%) but produced no obvious effect on cell cycle.</p><p><b>CONCLUSIONS</b>miR-146a may serve as a potential therapeutic target for colonic cancer for its role in inhibiting colonic cancer cell proliferation.</p>

Comparison of short- and long-term efficacy of three procedures in postoperative digestive tract reconstruction for upper gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the short- and long-term efficacy of three different procedures used for digestive tract reconstruction after radical gastrectomy for upper gastric cancer.</p><p><b>METHODS</b>Clinical data of 191 patients with upper gastric cancer undergoing radical gastrectomy in the Fujian Provincial Hospital between January 2000 and December 2012 were analyzed retrospectively. Surgical procedures were classified as total gastrectomy followed by Roux-en-Y esophagojejunostomy (TG-RY, n=123), proximal gastrectomy followed by esophagogastrostomy (PG-EG, n=40), and proximal gastrectomy followed by jejunal interposition (PG-JI, n=28). Clinicopathological characteristics, perioperative and long-term outcomes were compared among the three groups.</p><p><b>RESULTS</b>The operative time was shorter (178 vs. 248 and 224 min, P<0.05), and the intraoperative blood loss was less (194 vs. 323 and 265 ml, P<0.05) in PG-EG group than those in TG-RY and PG-JI groups. Early postoperative complications and hospital stay were comparable (both P>0.05). With respect to gastrectomy-associated symptoms, reflux and heartburn were more frequent in PG-EG patients, while dumpling syndrome was more frequent after TG-RY. Postoperative weight loss was not significantly different among three procedures (P>0.05), however, hemoglobin and serum albumin levels were lower in TG-RY patients (both P<0.05). The 5-year survival rate was similar (P>0.05).</p><p><b>CONCLUSIONS</b>Surgeons need to choose the proper procedure according to tumor features and patient condition. PG-JI should be the first choice in terms of fewer complaints and better nutrition. TG-RY tends to be used for larger and more advanced tumors. PG-EG is the most minimally invasive procedure and thus may be suitable for older and high-risk patients.</p>

Experimental therapeutic effect of combined cytokines on beagle dogs exposed to 4.5 Gy γ-rays / 中华放射医学与防护杂志

Objective To evaluate the effects of combined administration of recombinant human interleukin-11(rhIL-11),recombinant human G-CSF(rhG-CSF)and recombinant human interleukin-2 (rhIL-2)on acute radiation sickness(ARS)beagles.Methods Sixteen beagle were irradiated with 4.5 Gy60 Co γ-rays to establish ARS models,and were divided into irradiation control group,supportive care group and combined cytokines treatment group.After irradiation irradiation control group was given no treatment,the dogs in supportive care group received purely symptomatic treatment,while combined cytokines treatment group received rhIL-11 50μg/(kg·d)and rbG-CSF 10μg/(kg·d)subcutaneously(0-14 d)and rhIL-2 1×1 06 U/d(29-43 d)besides symptomatic treatment.Manifestation and characteristics of ARS beagles were observed,and the survival time were recorded.At last,post-mortem examination and histological examination were performed.Results All animals underwent nausea,diarrhea and fever.After irradiation,all animals in irradiation control group died in two weeks,and the mean survival time was 12.7 d,while only one died at 33 d in supportive care group.All dogs in combined cytokine group survived at 45 day after exposure,and their haematopoiesis and gastrointestinal tract were recovered.Conclusions Combination of rhIL-11 + rhG-CSF + rhIL-2 treatment could be significantly effective on ARS beagles irradiated by 4.5 Gy60 Co γ-rays,which could accelerate injured haemotopoiesis and intestinal tract recovery,increase the survival rate and improve the life quality of animals.

Initial research of screening for the differentially expressed proteins in beagles irradiated with 4.5 Gy60 CO γ-rays by two-dimensional gel electrophoresis and mass spectrometry / 中华放射医学与防护杂志

Objective To explore the mechanisms of cytokines on acute radiation disease in irradiated beagles.Methods The sera of beagles irradiated with 4.5 Gy γ-rays with cytokines treatment was collected at different time points post irradiation.The two-dimensional gel electrophoresis(2-DE)was used to isolate and compare the differentially expressed proteins in sera.HD-MS was used to analyze the differentially expressed proteins with significance,and the amino acid sequences should be determined. Results High resolution 2-DE gel map was obtained.There were six differentially expressed proteins in sera of irradiated beagles at different time points.Four protein spots were successfully identified by MS.A significant spot was identified as serum amyloid A(SAA)by HD-MS,with relative molecular mass of 13 077 and isoelectfie point of 6.26.Expression of SAA was not found 1 d pre-irradiation and 36 d postirradiation,but increased slightly 1 d(0.2166)and significantly 14 d post-irradiation(0.4577). Conclusions The expression of serum amyloid A was consistent with the process of acute radiation injury,which might indicate the turnover of the disease.

Clotting mechanism in beagles irradiated by 4.5 Gy γ-rays / 中华放射医学与防护杂志

Objective To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care,or supportive care and combined cytokines.Methods Sixteen beagles were divided into irradiation control group,Supportive care group and combined cytokines treatment group.Platelet aggregation test,thrombelagtography (TEG) and the time measurement were analyzed in vitro.Results In irradiation group and supportive care group,the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation,while those indexes in combined cytokines treatment group changed little.At 14 d post-irradiation,each parameter of TEG in irradiated group changed obviously.The values of r,k,r+k and M were elevated significantly,clotting time and the maximum coagulation time of thrombus delayed,the Ma value was decreased markedly,and the maximum elasticity amplitude of thrombus was diminished.All parameters in combined cytokines treatment group were better than those in supportive care group.The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation,while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group(P>0.05).Conclusions Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness.

Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles / 中华放射医学与防护杂志

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.

Studies on mechanism of treatment of granulocyte colony-stimulating factor,recombinant human interleukin-11 and recombinant human interleukin-2 on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles / 中华放射医学与防护杂志

Objective To investigate the mechanism of treatment of granulocyte colony-stimulating factor(rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2 (rhIL-2)on hematopoietic injuries induced by 4.5 Gy60 Coγ-ray irradiation in beagles,and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS).Methods Sixteen beagle dogs were given 4.5 Gy60 Co γ-ray total body irradiation(TBI),then randomly assigned into irradiation control group,supportive care group or cytokines+supportive care (abbreviated as cytokines)group.In addition to supportive care,rhG-CSF,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34+cells,cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry.Results After 4.5 Gy 60 Co γ-ray irradiation,the CD34+cells in peripheral blood declined obviously(61.3%and 52.1% of baseline for irradiation control and supportive care group separately).The cell proportion of nucleated cells in Go/G1 phase was increased notably(99.27% and 99.49% respectively).The rate of apoptosis(26.93% and 21.29% separately)and necrosis(3.27% and 4.14%,respectively)of nucleated cells were elevated significantly when compared with values before irradiation(P<0.05) 1 d post irradiation.When beagles were treated with cytokines and supportive care,the CD34+cells in peripheral blood were markedly increased(135.6% of baseline).The effect of G0/G1 phase blockage of nucleated cells became more serious(99.71%).The rate of apoptosis(5.66%)and necrosis(1.60%)of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure.Conclusions Cytokines maybe mobilize CD34+cells in bone marrow to peripheral blood,indce cell cycle block at G0/G1 phase and reduce apoptosis,and eventually cure hematopoieticinjuries induced by irradiation.

The regulation and its mechanism of Polydatin on the ?-adrenoreceptor in cardiac myocytes stimulated by lipopolysaccharide / 中国药理学通报

Aim To observe the effect of polydatin(PD) on the activities of ?-AR in cardiomyocytes under the stimulation of LPS. Methods Cardiac myocytes were isolated and cultured from neonatal rats. Radioligand binding assay and flow cytometry were used to detect the function of ?-AR. Results In control group, the density of ?-AR (B max) was 4.14?1.41 fmol?(1?105 cells) -1 and ?-AR affinity (K d) was (4.02?0.59) nmol?L -1. In LPS group, ?-AR density was down-regulated 〔B max=1.78?0.12 fmol?(1?105 cells) -1〕 and the affinity decreased (K d=23.88?2.34 nmol?L -1). In LPS+PD group, ?-AR B max was recovered to 3.37?0.36 fmol?(1?105 cells) -1 and the affinity increased (K d=3.44?0.44 nmol?L -1). In PD group, ?-AR functions had no significant difference with normal group 〔B max=2.76?0.32 fmol?(1?105 cells) -1 and K d=4.63?1.54 nmol?L -1〕. The ?-AR amount measured by flow cytometry showed the same change tendency as the radioligand binding assay. Conclusion ?-AR activities may be down-regulated during the pathological process of LPS treatment. PD could reverse the effects of LPS by up-regulating ?-adrenoreceptors.

Inhibitory effects of Interferon alfa-1b on human liver cancer cells in vivo / 解放军医学杂志

Objective To compare the effects of interferon alfa-1b(IFN?-1b) and pegylated IFN?-1b(PEG IFN?-1b) on inhibiting growth of human liver cancer cells in vivo.Methods Human liver cancer cells(HepG-2,2?l06/0.2ml) cultured in log phase were subcutaneously injected into the right rear flank of male BALB/C nude mice to establish the tumor model.After HepG-2 injection,the tumor growth was followed up for 14 days.The mice with HepG-2 tumor were randomly divided into placebo(n=7),PEG IFN?-1b(n=8) and IFN?-1b(n=8) groups.Mice received injection of placebo 0.2ml/mouse each time(three times a week),PEG IFN?-1b 150?g/mouse per injection(once a week) and IFN?-1b 50?g/mouse each time(three times a week),respectively,according to their grouping,and this regime lasted for five weeks.In order to evaluate anti-tumor activity,animals' body weight was measured every week,and the measurements of tumor volume and animals' body weight were continuously done till the mice were sacrificed at the end of the fifth week.Results PEG IFN?-1b and IFN?-1b induced a significant decrease in tumor volume and the animals' weight,the suppression rates onto tumor growth were 56%(2.190g vs.4.979g) and 42%(2.678g vs.4.979g),respectively.However,no significant difference was found in animals' weight among the three groups.Conclusion HepG-2(2?l06/0.2ml) injection into nude mice may induce a typical tumor model.PEG IFN?-1b(150?g/mouse per time,once a week) could significantly inhibit the growth of HepG-2 in vivo,and so does the IFN?-1b(50?g/mouse each time,three times per week).

Role of FPRL1 in the chemotaxis of polymorphonuclear leukocytes stimulated by LPS and its regulation by polydatin / 中国病理生理杂志

AIM: To investigate the chemotaxis mechanisms of polymerphonuclear leukocytes (PMNs) under the stimulation of LPS and its regulation by polydatin (PD). METHODS: Chemotactic chamber assay was used to investigate the regulatory role of formyl peptide receptor like-1 (FPRL1) in the chemotaxis of PMNs in response to LPS and PD. RESULTS: LPS increased the secretion of PMN chemotactic factor and up-regulated the function of formyl peptide receptor like-1. PD did not obviously affect the chemotactic factor secretion in normal PMN and the function of formyl peptide receptor like-1, but it significantly reduced the rise of chemotactic factor excretion in PMNs caused by LPS stimulation and PMNs transfected with formyl peptide receptor like-1. CONCLUSION: FPRL1 may mediate LPS-induced PMN chemotaxis, and PD regulates PMN chemotaxis by down-regulating the secretion of chemokine and the function of FPRL1 and may play a crucial role in the treatment of inflammation.

Effect of PD on the activity of protein kinase c of vascular smooth muscle cells / 中国药理学通报

Aim To study the influence of PD on the activity of PKC(protein kinase C) of VSMC during ischemia and hypoxia.Methods The hypoxia model was made by drawing off the oxygen of an enclosed acryl glass box and ischemia model was made by low sugar culture medium. Then the activity of PKC was measured by ?-scintillation counting instrument.Results It was found that the activity of PKC of cytoplasm in VSMC in ischemia and hypoxia situation increased (vs normal group P0.05 ).Conclusion PD can reverse the PKC activities induced by ischemia and hypoxia. It may be one of the mechanisms of PD to have antishock effect.

The reproduction of an improved model of rheumatoid arthritis in rats / 解放军医学杂志

Objective To reproduce a simple and practicable animal model of rheumatoid arthritis(RA)for evaluating the therapeutic effects of recombinant human interleukin-1 receptor antagonist(rhIL-1Ra).Methods The animal model of RA was reproduced in Wistar rats by intradermic injection of an admixture of bovine type Ⅱcollagen and Freund's complete adjuvant on the foot pad,tail,and back of the rats and the injections were repeated 7 days later.Results Two weeks after the second injection,all the extremities were markedly swollen.The diameter of ankle joints,the level of TNF-? in serum,and the size of the paws were increased obviously.There was destruction and absorption of the bone trabeculae of distal end of the tibia.There was also necrosis and fibrosis of cartilage of the joints.The articular space was narrowed.Thus RA model was successfully reproduced in rat.Conclusion Bovine type Ⅱcollagen and Freund's complete adjuvant were a favorable agent for the reproduction of RA model in rats.

Effect of recombinant human interleukin-11 on neutron irradiation injury of small intestine in mice / 解放军医学杂志

Objective To evaluate the effect of rhIL-11 on radiation injury to the intestinal epithelium and cells cycle of intestinal epithelial cell in mice irradiated with 3.5 Gy neutron. Methods The morphology of the small intestinal epithelium, crypt cells necrosis, and cell proliferation were observed of the epithelial cells of the irradiated mice. Cell cycle of the epithelial cells of the small intestine of the mice was examined by flow cytometry. Results rhIL-11 pretreatment before and treatment after irradiation could accelerate the repair of small intestinal mucosa in irradiated mice. G 2/M block which occurred in the irradiated small intestinal epithelial cells and the rhIL-11 treatment might significantly increased the proportion of cells at S phase. Conclusion rhIL-11 could significantly exert a preventive effect on the small intestine against radiation injury in neutron irradiated mice, with an impact on cell cycle of the intestinal epithelial cells.

Therapeutic effect of combination of rhIL-11 and rhG-CSF on acute radiation sickness produced by neutron irradiation in dogs / 解放军医学杂志

Objective To evaluate the therapeutic effects of combined recombinant human IL-11(rhIL-11) and recombinant human G-CSF (rhG-CSF) on the neutron-irradiated dogs. Methods 18 male beagle dogs were divided into radiation control group (C, n=7), symptomatic treatment group (S, n=4), and combination therapy group (T, n=7). All dogs were exposed to total body 2Gy 90% neutron radiation. From the first day after radiation, the animals of group T received rhG-CSF 10?g/(kg?d) and rhIL-11 50?g/(kg?d) subeutaneously for 14d and 21d respectively. The cell counts of peripheral blood and CFU-GM of bone marrow were carried out. Results All animals of group S and T survived, however, the survival rate of group C was only 57%. The cellcounts of T group peripheral blood cells (white blood cell at any time point , the platelet and red blood cell of recovery phase) were higher than that of C or S group. The count of T group bone marrow CFU-GM was 6 fold higher than that of group C or S on day 1, and still 1.75, 1.46 fold higher than that group C or S, respectively, on day 33. Conclusion the combination therapy of rhIL-11 and rhG-CSF significantly raised the white cell and platelet counts in ARS dogs induced by neutron irradiation by accelerating the recovery of bone marrow hematopoietic function.

The effect of interferon ? with different structures on ACHN tumor suppression / 解放军医学杂志

Objective To evaluate the anti-tumor activity of interferon ? with different structures including pegylated interferon ?-1b (PEG IFN ?-1b), pegylated interferon ?-2b (PEG IFN ?-2b) and natural interferon ? (IFN ?) in male BALB/C nude mice with human renal adencarcinoma (ACHN) tumor. Methods Athymic BALB/C nude mice were received a subcutaneous injection of ACHN cells (2?106/0.2ml) on the rear flank. After four weeks, the size of tumor reached a mean volume of 50-100 mm3, and the interferon was administrated. The mice with tumor were divided into four groups, and were administrated with placebo (0.2ml/mouse thrice weekly), IFN ?-1b (50?g/mouse thrice weekly), PEG IFN ?-1b (150?g/mouse once weekly) and PEG IFN?-2b (150?g/mouse once every week), respectively, for five weeks. The tumor volumes were measured weekly prior to treatments until the end of the fifth week. All mice in each group were sacrificed to measure the weight of the residual tumor. The anti-tumor activity of IFN ? in vivo was evaluated by studying their ability to reduce the volume and weight of tumor. Results IFN ? may significantly reduce the volume and weight of ACHN tumor in mice. The average tumor weight was 0.422g in placebo group, while 0.263g, 0.235g and 0.219g in the groups treated with PEG IFN ?-1b, IFN ?-1b and PEG IFN ?-2b, respectively. No significant difference was found among the three groups treated with IFN ?. Moreover, the volume of tumor in three groups treated with IFN ? was significant reduced than that in placebo group. Conclusion IFN ? with different structures have showed the similar ability of ACHN tumor suppression at the dosage of 150?g per week.