Research Advance of the Mechanisms, Clinical Characteristics and Treatment Strategy of Coagulation Dysfunction in Hemophagocytic Lymphohistiocytosis --Review / 中国实验血液学杂志

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by uncontrolled proliferation of activated macrophage, and secreting high amounts of inflammatory cytokines which lead to multi-organ dysfunction syndrome. HLH patients often show different clinical characteristics during the disease was progressed, in which coagulopathy were the most common, including thrombocytopenia and hypofibrinogenemia, those are the major cause of death in patients, and the clinicians should increase awareness of the mechanisms, clinical characteristics, prognosis and treatment. In this review, the above problems are briefly summarized, to deepen understanding of the HLH related coagulation dysfunctions, and early identification and treatment to reduce mortality, so as to provide more opportunities for HLH patients to recieve subsequent treatment.

Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia: Pathological Mechanism and Treatment Progress---Review / 中国实验血液学杂志

Chronic lymphocytic leukemia (CLL) patients usually show immune dysfunction, which often leads to autoimmune hemocytopenia. Immune thrombocytopenia (ITP) is one of the common complications. The pathogenesis of CLL-related ITP is complex and has not been fully elucidated. At present, the researches mainly focus on humoral immunity, cellular immunity and innate immune disorders. Recent studies suggest that genomic abnormalities and microRNAs are also involved in CLL-related ITP. Traditional ITP standard therapy has a poor effect on CLL-related ITP. Chemotherapy or monoclonal antibody therapy against the primary pathogenesis of CLL can effectively treat thrombocytopenia, and the emergence of new targeted drugs also provides new treatment options for the disease. In this paper, the progresses of CLL-related ITP pathogenesis, prognosis and treatment in recent years are reviewed.

Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway / 华中科技大学学报（医学）（英德文版）

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

Risk factors for recurrence of ovarian endometriomas after surgical excision / 华中科技大学学报（医学）（英德文版）

Ovarian endometrioma is a common form of endometriosis, which may cause infertility, dysmenorrhea and pelvic pain in women of reproductive age. Although surgery is the treatment of choice for endometriomas, recurrence poses a formidable frustration. This study investigated potential risk factors of endometriomas recurrence, aiming to better understand its pathogenesis. A total of 307 patients with endometriomas were followed up for an average of 28.6 months and the 1-, 2- and 3-year cumulative recurrence rate was 9.5%, 21.9%, and 29.2%, respectively. Twenty-one potential risk factors for endometriomas recurrence were evaluated using Cox's proportional hazards models. Total revised American Fertility Society (rAFS) score was significantly associated with higher recurrence (OR=1.858, 95% CI=1.122-3.075, P=0.016), as well as younger age at surgery (OR=0.953, 95% CI=0.915-0.992, P=0.020). Semiradical surgical treatment was defined as surgical removal of cyst plus hysterectomy with preservation of bilateral or unilateral ovary, and was a significant factor that was associated with lower recurrence than the conservative surgery (OR=0.318, 95% CI=0.107-0.951, P=0.040). Postoperative pregnancy was favorable factors for disease recurrence (OR=0.217, 95% CI=0.102-0.460, P=0.000). The results suggest that endometrioma recurrence is inversely associated with age at surgery and postoperative pregnancy, and may correlate with total rAFS score and conservative surgery method.

Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway / 华中科技大学学报（医学）（英德文版）

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

Risk factors for recurrence of ovarian endometriomas after surgical excision / 华中科技大学学报（医学）（英德文版）

Ovarian endometrioma is a common form of endometriosis, which may cause infertility, dysmenorrhea and pelvic pain in women of reproductive age. Although surgery is the treatment of choice for endometriomas, recurrence poses a formidable frustration. This study investigated potential risk factors of endometriomas recurrence, aiming to better understand its pathogenesis. A total of 307 patients with endometriomas were followed up for an average of 28.6 months and the 1-, 2- and 3-year cumulative recurrence rate was 9.5%, 21.9%, and 29.2%, respectively. Twenty-one potential risk factors for endometriomas recurrence were evaluated using Cox's proportional hazards models. Total revised American Fertility Society (rAFS) score was significantly associated with higher recurrence (OR=1.858, 95% CI=1.122-3.075, P=0.016), as well as younger age at surgery (OR=0.953, 95% CI=0.915-0.992, P=0.020). Semiradical surgical treatment was defined as surgical removal of cyst plus hysterectomy with preservation of bilateral or unilateral ovary, and was a significant factor that was associated with lower recurrence than the conservative surgery (OR=0.318, 95% CI=0.107-0.951, P=0.040). Postoperative pregnancy was favorable factors for disease recurrence (OR=0.217, 95% CI=0.102-0.460, P=0.000). The results suggest that endometrioma recurrence is inversely associated with age at surgery and postoperative pregnancy, and may correlate with total rAFS score and conservative surgery method.

Association of FOXP3 gene polymorphism in Chinese women with endometriosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between single nucleotide polymorphisms (SNPs) of forkhead box P3 gene (FOXP3) and endometriosis in Chinese Han women from central China.</p><p><b>METHODS</b>MassARRAY IPLEX and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technique was used to determine the genotypes of FOXP3 gene in 314 patients with endometriosis and 358 healthy controls.</p><p><b>RESULTS</b>Genotypes of C/T polymorphism for the rs2280883 locus, A/C for the rs3761548 locus, and C/T for the rs3761549 locus were determined. No significant difference was detected in distribution of genotypes CC, CT and TT (P=0.770, OR=0.960; P=0.923, OR=1.013) and frequencies of C and T alleles (P=0.772, OR=0.960; P=0.925, OR=1.013) for rs2280883 and rs3761549 between the two groups. And no significant difference was detected in distribution of genotypes AA, AC and CC (P=0.762, OR=0.958) and frequencies of A and C alleles (P=0.715, OR=0.950) for rs3761548 was detected between the two groups. Based on r-AFS classification, the patients were divided into two groups (respectively with I-II stage and III-IV stage endometriosis). Again, no significant difference was detected in distribution of genotypes CC, CT and TT (P=0.454, OR=1.198, P=0.526, OR=0.909; P=0.220, OR=0.750, P=0.548, OR=1.094) and frequencies of C and T alleles (P=0.473, OR=1.215, P=0.532, OR=0.912; P=0.204, OR=0.737, P=0.558, OR=1.089) for rs22080883 and rs3761549 loci between the two patient groups. No association was found between distribution of genotypes AA, AC and CC (P=0.431, OR=1.211; P=0.508, OR=0.905) and frequencies of A and C alleles (P=0.417, OR=1.226; P=0.516, OR=0.908) for rs3761548 locus between the two patient groups.</p><p><b>CONCLUSION</b>Our study has failed to found any association between FOXP3 gene polymorphisms rs2280883, rs3761548 and rs3761549 with endometriosis in Chinese Han patients.</p>

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Antitumor and antimetastatic effect of antimicrobial peptide conjugated with tumor homing peptide TMTP1 on the transplanted prostate cancer and gastric cancer in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Due to their lower risk for induction of resistance, antimicrobial peptides with selective anticancer effect could be developed into a new generation of anticancer drugs. We conjugated an antimicrobial peptide with tumor-targeting peptides (TMTP1) to explore whether it has inhibiting effect on the progression and metastasis of transplanted prostate cancer and gastric cancer in nude mice.</p><p><b>METHODS</b>Subcutaneously transplanted human prostate cancer and orthotopically transplanted human gastric cancer in nude mice were prepared. 50 µmol/L PBS (control group), 50 µmol/L TMTP1 (TMTP1 group) or 50 µmol/L TMTP1-GG-D(KLAKLAK)(2) (treatment group) were injected i.p. to the three groups of nude mice, respectively. The binding ability of the novel fusion polypeptide TMTP1-GG-D(KLAKLAK)(2) to the tumors and its antitumor effect were assessed by measurement of tumor volume, histopathological examination of the tumor tissues, testing apoptosis index of tumor cells with TUNEL staining, and survival curve plotting of the mice.</p><p><b>RESULTS</b>The median survival time of subcutaneous prostate cancer-bearing mice was 50 days in the control group, 55 days in the TMTP1 group, and 70 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.05). The median survival time of the subcutaneous gastric cancer-bearing mice was 25 days in the control group, 30 days in the TMTP1 group, and 45 days in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume in the subcutaneous prostate cancer-bearing mice was (2.5 ± 0.3)cm(3) in the control group, (1.8 ± 0.2) cm(3) in the TMTP1 group, and (0.3 ± 0.1)cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). The tumor volume of the subcutaneous gastric cancer-bearing mice was (3.8 ± 0.4) cm(3) in the control group, (3.2 ± 0.2)cm(3) in the TMTP1 group, and (0.4 ± 0.1) cm(3) in the TMTP1-GG-D(KLAKLAK)(2) group (P < 0.01). Large tumors were observed in the stomach of the orthotopic gastric cancer-bearing mice of the control and TMTP1 groups. The tumor volume of the TMTP1-GG-D(KLAKLAK)(2) group was obviously reduced. White metastases in the liver, spleen and abdominal wall were observed in the control and TMTP1 groups (P < 0.01). TUNEL staining revealed that the apoptosis index of the control group was (31.9 ± 1.5)%, TMTP1 group (37.2 ± 2.3)% and TMTP1-GG-D(KLAKLAK)(2) group (69.7 ± 2.1)% (P < 0.01).</p><p><b>CONCLUSIONS</b>The results of our study demonstrate that the novel fusion peptide of antimicriobial peptide conjugated with TMTP1 can effectively inhibit tumor progression and metastasis, therefore, is promising to be a novel effective anticancer drug.</p>

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Effect of blocking of ROCK-1, an effector of small G protein Rho, on the malignant behavior of ovarian tumor cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the possible role of ROCK-1 in ovarian cancer invasion and metastasis.</p><p><b>METHODS</b>ROCK-1 ASODN was transfected into SW626 and Caov-3 cell lines mediated by Lipofectamine 2000. The expressions of ROCK-1 mRNA and protein were detected by RT-PCR and Western-blot assay. Boyden chamber was used to assess the effect of ROCK-1 ASODN on the invasion and migration of the cell lines. The changes in the adhesion and proliferation of the transfected cells were detected by MTT assay.</p><p><b>RESULTS</b>The expressions level of ROCK-1 mRNA and protein in the cell lines were decreased significantly after transfection at doses of 10 micromol/L and 20 micromol/L ROCK-1 ASODN. When compared with the control group, the invasion capability of transfected cells was inhibited to an extent of 75.6% +/- 3.8% and 54.7% +/- 2.9%, respectively, for SW626 cell line, and 68.8% +/- 4.7% and 50.0% +/- 4.5% for Caov-3 cell line, respectively. The random migratory activity of these two cell lines was inhibited by 80.0% +/- 1.3%, 63.7% +/- 1.9%, 72.5% +/- 3.4% and 55.9% +/- 2.5%, respectively, and the inhibition of chemotaxis activity of the two cell lines was 83.9% +/- 1.4%, 64.1% +/- 1.3%, 72.5% +/- 3.4% and 54.5% +/- 1.9%, respectively. No significant difference was found in the adhesion and proliferation of the cells transfected with ROCK-1 ASODN and control cells.</p><p><b>CONCLUSION</b>The expression of ROCK-1 was closely related to the invasion capability and migratory activity of ovarian cancer cells. ROCK-1 may play a crucial role in invasion and metastasis of ovarian cancer.</p>

Influence of metastasis suppressor gene KAI1 on proliferation and invasion of endometrial carcinoma cells / 中国肿瘤生物治疗杂志

Objective:To investigate the influence of metastasis suppressor gene KAI1 on the proliferation,invasion and metastasis of endometrial carcinoma cell line AN3CA and HEC-1-B.Methods:The KAI1 cDNA was transfected into human endometrial carcinoma cells AN3CA and HEC-1-B via Lipofectamine 2000.The expression of KAI1 protein was ex- amined by Western blotting and flow cytometry before and after transfection.The proliferation ability of AN3CA and HEC- 1-B cells was observed by MTT assay and anchorage-independent growth assay.The changes of cell invasive ability were studied by transwell assays.Results:Stable expression of KAI1 protein was observed in AN3CA and HEC-1-B cells and on their surface after transfection with pcDNA3-KAI1 plasmid.Cells transfected with blank plasmid formed more colonies and had a larger size,with the colony forming rates being(54.2?3.1)% for AN3CA cells and(52.7?4.3)% for HEC- 1- B cells;the doubling time of AN3CA and HEC-1-B cells were 21.3 h and 20.1 h,respectively.Cells transfected with pcDNA3-KAI1 formed less colonies and had a smaller size,with the colony forming rates being(37.4?5.1)% for AN3CA cells and(32.1?3.7)% for HEC-1-B cells;the doubling time of AN3CA and HEC-1-B cells were 43.7h and 45.2 h,respectively.The cell proliferation abilities and colony-forming ability were significantly different between the two groups(P

Recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene transfer followed by ganiciclovir administration effectively inhibits growth of human small-cell lung cancer in a murine xenotransplant model / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer in combination with ganiciclovir (GCV) is one of the major gene therapy strategies to eradicate tumor cells. This study was aimed at determining the in vivo anti-tumor efficacy of ADV-TK in combination with ganiciclovir (GCV).</p><p><b>METHODS</b>A murine xenotransplant model of human small-cell lung cancer was established. ADV-TK was administrated by intra-tumoral injection followed by intraperitoneal administration of GCV. The anti-tumor efficacy was evaluated using index of tumor volume, relative tumor volume, tumor weight, relative tumor proliferative rate, and tumor growth curve.</p><p><b>RESULTS</b>In the presence of GCV, ADV-TK effectively inhibited growth of human small-cell lung cancer in a dose-dependent fashion. An inhibition plateau was not observed within the current dosage range. ADV-TK at a dose of 6.0 x 10(9) viral particles/kg in the presence of GCV lead to 64.6% and 81.7% inhibition of tumor growth respectively in two independent experiments. ADV-TK or GCV alone caused slight inhibition of tumor growth, which was not statistically significant as compared to the negative control group (P > 0.05).</p><p><b>CONCLUSION</b>ADV-TK followed by GCV is highly efficacious to inhibit the growth of human small-cell lung cancer in a murine xenotransplant model. The results presented here are encouraging to warrant a further clinical evaluation of the potential therapeutic benefits of this strategy.</p>

Correlation of expression of RhoA (RhoC and their effector ROCK-1 with malignant phenotype of ovarian cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of RhoA, RhoC and their effector ROCK-1 in four ovarian cancer cell lines in vitro and their correlation with invasiveness.</p><p><b>METHODS</b>Expression of RhoA, RhoC and ROCK-1 mRNA and protein in four ovarian cancer cell lines SW626, Skov-3, A2780 and Caov-3 was detected by RT-PCR and Western blot assay. Invasion assay was done in Boyden chamber.</p><p><b>RESULTS</b>The expression levels of RhoA, RhoC and ROCK-1 mRNA and protein varied in the four different cell lines examined. The expression level of RhoC, but not RhoA and ROCK-1, was significantly correlated with the invasive capability of these cells in vitro (r = 0.95, P < 0.01). Expression of RhoA at the level of transcription was not correlated with that at the translation level. The expression of RhoA and RhoC did not correlate with that of ROCK-1.</p><p><b>CONCLUSION</b>Expression level of RhoC may serve as an independent parameter in evaluating metastasis and become a new target in inhibiting ovarian cancer metastasis.</p>

Significance of expression of T lymphoma invasion/metastasis gene in ovarian cancer cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the role of T lymphoma invasion/metastasis gene 1 (Tiam1) and protein in ovarian tumor cells.</p><p><b>METHODS</b>Expressions of Tiam1 mRNA, Rac1 mRNA, and Tiam1 protein in four ovarian tumor cells A2780, Caov3, Skov3, and SW626 were studied by using RT-PCR and Western blot, respectively. The cell migration ability was analyzed by in vitro invasion assay.</p><p><b>RESULTS</b>Expressions of Tiam1 mRNA and protein, as well as Rac1 mRNA were detected in all four ovarian tumor cells. There was a strong direct correlation between the levels of Tiam1 and Rac1 mRNA expression and migration potentials of all four ovarian cancer cells in vitro experiments. The increased expressions of Tiam1 mRNA were coincident with those of Rac1 mRNA, with a parallel relationship (P = 0.003, r = 0.874). Levels of Rac1 mRNA expression were significantly correlated with the potentials of tumor cell migration (P = 0.042, r = 0.814).</p><p><b>CONCLUSION</b>Tiam1-Rac1 signaling pathway plays a positive role in assessing tumor cell invasion and metastasis and provides a new target for gene therapy of ovarian cancer.</p>

Mdr-1 ribozyme in the reversal of multidrug resistance in human ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the mechanism of multidrug resistance and its reversal by mdr-1 ribozyme in human ovarian cancer.</p><p><b>METHODS</b>The expression of mdr-1 and p-glycoprotein (p-gp) was studied by confocal laser microscope (Confocal), RT-PCR and Western blot analysis in adriamycin-resistant human ovarian cancer cell line (A2780/ADM) and adriamycin-sensitive one (A2780). The mdr-1 ribozyme was transfected into the A2780/ADM by Lipofectamine 2000 to overcome the multidrug resistance in ovarian cancer.</p><p><b>RESULTS</b>The expression of mdr-1 mRNA and p-gp in A2780/ADM was significantly higher than that in A2780. The expression of mdr-1 mRNA and p-gp in A2780/ADM was lowered after being transfected by mdr-1 ribozyme.</p><p><b>CONCLUSION</b>Multidrug resistance of A2780/ADM, possibly being caused by overexpression of mdr-1 gene, can be partially reversed by mdr-1 ribozyme.</p>

The role of GSK-3?in apoptosis induced by proteasome inhibitors combined with paclitaxel in ovarian cancer cells and its possible mechanism / 中国癌症杂志

Background and purpose:Proteasome inhibitors such as bortezomib,represent an interesting new class of potential anticancer drugs.In the present study,we explored the sensitivity of ovarian cancer cell line SKOV3 to paclitaxel,proteasome inhibitors and their combination,and also studied the involvement of GSK-3?/Mcl-1 signaling pathway in the regulation of apoptosis induced by those agent.Methods:Methyl thiazolyl tetrazolium (MTT)assay was applied to examine the cell viability,Annexin-V/PI apoptosis detection kit was used to determine the apoptosis rate of different groups,and western blot assay was introduced to evaluate the expression levels of phosphorylated GSK-3?and Mcl-1.Results:In the MTT assay,the cell viability ratios of combination group at serial time points from 12 to 72 hr were(65.2?5.8)%,(58.3?14.4)%,(35.3?5.0)%,(19.2?1.5)% and(11.4?2.5)%,and there were significant differences as compared to the treatment of paclitaxel alone(P