[Show abstract][Hide abstract] ABSTRACT: Upregulation of nuclear factor-κB (NF-κB) in colorectal carcinoma (CRC) accelerates tumor growth, whereas, irinotecan (CPT-11)-induced NF-κB activation reduces chemosensitivity and weakens the anti-colorectal cancer function itself, while proteasome inhibitors can inhibit NF-κB and improve the effect of chemotherapy. Carfilzomib (CFZ) is a novel proteasome inhibitor that has been recently approved by the FDA and is in clinical use for the treatment of multiple myeloma, but little is known about its activity against CRC. The aim of the present study was to explore whether CFZ alone or in combination with CPT-11 is effective in CRC treatment. We evaluated the novel therapeutic ability and mechanism of action of CFZ in CRC in vitro and in vivo. SW620 cells were incubated with CFZ alone or in combination with CPT-11. Cell proliferation was assessed by WST-1 and clonogenic assays, the cytotoxic interaction was assessed with a combination index (CI). Cell cycle progression was analysed with flow cytometry. Cell apoptosis was evaluated by detecting the Annexin V/propidium iodide (PI) ratio, caspase 3 and CD95 expression, and with TUNEL staining. Cell migration and invasion was determined with a wound-healing assay and a Transwell matrix penetration assay. A CRC xenograft model was established to monitor tumor growth. EMSA was used to analyse NF-κB activation and western blot analysis was used to detect the protein levels of related signaling factors. CFZ significantly inhibited the growth of SW620 cells, and had synergistic inhibitory effects with CPT-11 on survival and colony formation; possibly by inhibition of NF-κB activation, MEK/ERK and PI3K/AKT pathway factor dephosphorylation and survivin downregulation. Co-administration of CFZ and CPT-11 induced G2/M arrest, increased p21WAF1/CIP, and decreased mutant p53 and cdc25c expression. Induction of apoptosis was accompanied by marked increases in PARP cleavage, caspase 3 activation, an increase of CD95 and p-p38, and ATF3 activation. Combination treatment lowered the invasive and migration ability of SW620 cells, reduced MMP and increased TIMP protein expression. Finally, co-administration of CFZ and CPT-11 suppressed tumor growth and increased apoptosis compared with single-agent treatment in SW620 xenograft models correlated with NF-κB downregulation. Carfilzomib alone or in combination with CPT-11 is effective against colorectal cancer through inhibition of multiple mechanisms related to NF-κB, and could be a potential novel therapy for CRC.
[Show abstract][Hide abstract] ABSTRACT: Inhibitor of DNA-binding protein 1 (ID1) is commonly abnormally overexpressed in colorectal cancer (CRC); yet, the functional significance of ID1 in the growth and invasive properties of CRC cells remains largely unclear. The present study investigated the effects of ID1 downregulation on the cell growth and metastatic features of CRC. Using lentiviral shRNA infection, stable ID1-knockdown (KD) HCT116 and SW620 cells, human metastatic CRC cell lines, were created. In vitro, the migration/invasion capacity of the ID1-KD CRC cells was assessed by a wound healing assay. The activities of MMP2 and MMP-9 were measured by gelatin zymography. The expression of CXC chemokine receptor 4 (CXCR4), PCNA and survivin were determined by immunoblot analysis and qRT-PCR. The effects of ID1 knockdown on tumor growth and hepatic metastasis were demonstrated by a xenograft study in mice. The results showed evident decreases in proliferation, migration and invasion and an increased apoptosis rate in the ID1-KD CRC cells. Similarly, ID1 knockdown significantly decreased mRNA and protein levels of PCNA, survivin, CXCR4, MMP2 and MMP9. Overexpression of CXCR4 antagonized the negative effect on the migration and invasion abilities of the ID1-KD cells. As compared with the control, ID1 knockdown prevented tumor growth and profoundly suppressed hepatic metastasis in vivo. The present study demonstrated the significance of ID1 in colon cancer progression, and its effect on tumor invasiveness and metastatic properties may be partly dependent on CXCR4.
[Show abstract][Hide abstract] ABSTRACT: Mutation analysis in breast cancer has failed to explain the inactivation of RhoBTB2, a candidate breast cancer tumor suppressor gene on chromosome 8p. Some breast cancer‑related genes in this region become inactivated by hypermethylation, and hypermethylation of RhoBTB2 abrogates its expression in bladder cancers. The aim of the present study was to determine whether RhoBTB2 was silenced by methylation in breast cancer. Nested methylation‑speciﬁc PCR (nMSP) and quantitative reverse transcription PCR were used to analyze the methylation status and mRNA levels of RhoBTB2 in 50 paired breast cancer and normal tissues and the results were correlated with clinicopathological characteristics. Promoter methylation and the downregulation of RhoBTB2 mRNA was observed in tumor tissues (P<0.001). mRNA levels were decreased in samples with methylation (χ2 = 15.751, P<0.001). RhoBTB2 methylation was observed preferentially in progesterone receptor (PR)‑negative samples (P<0.05). The results demonstrated that aberrant methylation of RhoBTB2 may be responsible for the suppression of RhoBTB2 mRNA expression in breast cancer, a significant event during the genesis of breast cancer that correlated with PR status.
International Journal of Molecular Medicine 12/2013; · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To define mitochondrial protein markers related to liver cancer. EXPERIMENTAL DESIGN: Mitochondrial sub-proteomes of 20 patient-derived liver carcinoma and tumor-free control tissues were performed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF/TOF. The altered patterns of three identified proteins were validated by Western blot and immunohistochemistry. RESULTS: The results showed that compared with tumor-free control samples, nine proteins were down-regulated and six proteins were up-regulated in carcinoma samples. The increased expression of Arg1 mRNA and protein was validated by Western blot, Q-RT-PCR, paraffin tissue microarray and immunohistochemistry. Furthermore, a literature review shows that 10-kDa heat shock protein (Hsp10), single-stranded DNA-binding protein (SSBP1), and peptidyl-prolyl cis-trans isomerase A (PPIA), which were identified as being increased in the tumor samples in this study, may be closely related to protein folding and translation. CONCLUSIONS AND CLINICAL RELEVANCE: These results show that in addition to changes in the signaling pathways, such as the Ras-Raf-MEK-ERK pathway, altered mitochondrial DNA replication and protein folding in liver cancer are also worth studying further. Collectively, these results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the investigation of their potential as therapeutic and prognostic markers. Further studies focusing on these proteins will be used to predict treatment response and reverse the apoptosis resistance.
[Show abstract][Hide abstract] ABSTRACT: Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activities. However, the underlying molecular mechanism(s) involved in the anticancer effect of this herb are poorly understood. Angiogenesis is important in the development of cancer. The main features of angiogenesis are increased vasculature and overexpression of vascular endothelial growth factor (VEGF). In the present study, the effects of M. tenacissima extract (MTE) on human umbilical vein endothelial cell (HUVEC) proliferation, migration and capillary-like tube formation were investigated in vitro and using the chick embryo chorioallantoic membrane (CAM) assay in vivo. It was observed that MTE inhibited the proliferation of HUVECs by blocking the cell cycle progression from G1 to S. In addition, MTE inhibited the migration and tube formation of HUVECs. MTE treatment decreased the VEGF-A expression in human hepatoma cells (HepG2), as well as the expression of VEGF-A and VEGF receptor (VEGFR)-2 in HUVECs. MTE exposure in the CAM was able to reduce the formation of blood vessels in chick embryos. Overall, the present data suggest that extracts of M. tenacissima may serve as potential anti-angiogenesis agents.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of Xiaoaiping Injection (XAP) on advanced hepatocellular carcinoma (HCC) in patients.
Sixty-eight patients with advanced HCC were assigned to a control group of 36 and a treatment group of 32. The control group was treated with best supportive treatment (BST) and the treatment group was given XAP plus BST. XAP was administered daily by i.v. and the treatment course was lasted for 30 days for both groups. The immediate therapeutic efficacy, Karnofsky performance status (KPS) scores, and the changes in immunity indicators (CD3+, CD4+ and CD8+ T cells) were measured and compared before and after treatment. The progression-free survival (PFS) rate and overall survival (OS) rate in the 2 groups were analyzed.
The immediate therapeutic efficacy and KPS of the treatment group were better than those in the control (P < 0.05). Patients in the treatment group had higher percentages of CD3 and CD4 T-lymphocytes in peripheral blood than those in the control group (P < 0.05). The median survival time was 27.0 weeks in the treatment group and 24.5 weeks in the control group. The 6-months cumulative survival rates in the treatment and control groups were 33.3% and 25.0%, respectively, with no significant difference (P > 0.05). The PFS was 18 weeks in the treatment group and 15 weeks in control group (P < 0.05).
XAP enhances the quality of life (QOL) of patients with advanced HCC, improves their immunity and extends their PFS.
Journal of Traditional Chinese Medicine 02/2013; 33(1):34-8. · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1 % (95 % confidence interval, CI, 40.1-68.3 %), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8 % (95 % CI 58.0-83.7 %), and the 5-year OS was 41.7 % (95 % CI 27.7-55.6 %). The 2-year progression-free survival rate (PFS) was 37.5 % (95 % CI 23.8-51.2 %), and the 5-year PFS was 25.0 % (95 % CI 12.8-37.3 %). The median progression-free survival was 8.8 months (95 % CI 0-20.3 months), and the median overall survival was 40.6 months (95 % CI 22.6-58.6 months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4(+) counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P = 0.015). Myelosuppression was the main side effect; the incidence of grade 3-4 anemia was 8.3 %; leukopenia, 37.5 %; and thrombocytopenia, 48.3 %. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4(+) lymphocyte counts, and did not promote HIV-1 viral replication.
Annals of Hematology 07/2012; 91(11):1757-63. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression of the activating and inhibitory receptors on the surface of NK cells of primary hepatocellular carcinoma and its adjacent tissues, and the relationship between these two receptors and occurrence and development of primary liver cancer was analyzed.
The number and activity of the NK cells, the expression of the activating and the inhibitory receptors on the surface of those cells were detected flow cytometry and immunohistochemistry, which were obtained from 52 cases of primary hepatocellular carcinoma and its adjacent tissues. The relative analysis was done between those results and clinical relative factors.
In the tissues of primary hepacellular carcinoma, the number of NK cells is lower than that in the adjacent tissues obviously (P<0.01); the expression of activating receptors, NKG2D and NKP44, is also lower than that in the adjacent tissues obviously (P<0.05); the expression of inhibitory receptors, CD158b and CD159a, is significantly higher than that in the adjacent tissues (P<0.05). A negative correlation was found between the expression of NKG2D, NKP30 and NKP44 and the clinical stage of the liver cancer. The expression of NKG2D, NKP30 and NKP44 was higher in patients with early and middle stages (P<0.05). The content of the inhibitory receptors of NK cells, CD158b and CD159a, is higher in tissues from patients with advanced cancer stage (P<0.05). That's also correlated with the level of AFP and the HBsAg. There is no significant statistical difference between the expression of NK receptors and the distant metastasis, tumor differentiation as well as the tumor size (P>0.05).
The decrease of NK cell numbers and the activating NK cell receptors and the increase of the inhibitory receptors would be relevant to the incidence of primary hepacellular carcinoma.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 05/2012; 28(5):529-32.
[Show abstract][Hide abstract] ABSTRACT: The relationship between KRAS and NF-κB in colorectal cancer is not clear. Western blotting was used to determine whether KRAS knockdown in SW620 cells altered the levels of NF-κB-p65 and other molecules. Furthermore, we investigated the association between the KRAS status and NF-κB expression in 167 colorectal cancers tumor tissues and their correlation with overall survival (OS) of patients with KRAS mutations and activated NF-κB. RAS, p-ERK, p-IκBα and p65 expression was decreased in SW620 cells with KRAS knockdown. The MEK inhibitor U0126 downregulated p-ERK, p-IκBα and p65 levels in SW620 cells. p65 activation in tumors with KRAS mutations was higher (50.8%) than in tumors with the wild-type KRAS gene (30.6%) (P=0.012). Compared to patients with other types of tumors, OS was lower (median 28.4 months) in patients with KRAS mutations and NF-κB activation, vs. a median of 46.3 months in patients with other types of tumors (P=0.005). NF-κB activation was reduced in SW620 cells with KRAS knockdown, possibly via the RAS-ERK-IκBα pathway. The presence of both KRAS mutations and the active form of NF-κB in CRC tumors indicates poor patient prognosis.
[Show abstract][Hide abstract] ABSTRACT: Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent.
To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients.
NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed.
Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005.
NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.
Digestive Diseases and Sciences 04/2012; 57(9):2325-33. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate through retrospective analysis the efficacy and toxicity of combination chemotherapy with etoposide, vincristine, doxorubin and dexamethasone (EVAD) as second-line therapy in patients with advanced AIDS-related Kaposi's sarcoma (AIDS-KS) after failure of first-line chemotherapy.
Eighty-eight patients with poor-risk AIDS-KS were treated intravenously with combination chemotherapy with EVAD; etoposide at a dose of 100 mg/m(2) on three consecutive days, vincristine 1.4 mg/m(2) with a maximum single dosage of 2.0 mg on day one, doxorubicin 30 mg/m(2) on day one and dexamethasone 40 mg on three consecutive days, with a three week cycle. All eligible patients had relapsed or progressed after prior two to six cycles of combination chemotherapy with doxorubicin, bleomycin and vincristine (ABV) or bleomycin and vincristine (BV).
Assessment of the response of all the patients was made. The overall objective response rate was 59.1% (95% CI 48.83-69.37%), with five complete responses and 47 partial responses. Twenty-six cases of stable disease and 10 of progressive disease were observed in the remaining patients. The median follow-up period was 27 months (range 8-52 months). The median time to progression was 6.80 months (95% CI 2.04-11.56 months), and the median overall survival was 14.24 months (95% CI 10.26-18.22 months). Leucopenia was seen in 92.0% of patients, of which 20 patients had grade 3 and 12 had grade 4. Conclusions Combination chemotherapy with EVAD offers a new, active and safe therapeutic approach for the treatment of advanced AIDS-related KS.
Journal of Cancer Research and Clinical Oncology 12/2011; 138(3):425-30. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the efficacy and safety of adjuvant intraperitoneal perfusion chemotherapy (IPC) in resectable gastric cancer through retrospective analysis.
Three hundred and sixty T2-4bN0-3M0 resectable gastric cancer patients were included in this study. One hundred and eighty-four patients used systemic chemotherapy combined with IPC (IP+ group) and 176 systemic chemotherapy only (IP- group).
With a median of 49.9 months of follow-up, the 5-year overall survival in IP+ patients was significantly better than in IP- patients (60.4 vs. 42.9%; p = 0.001), and the average progression-free survival in IP+ patients was significantly longer than in IP- patients (60.5 vs. 46.2 months; p = 0.001). Relapse rates of peritoneal carcinomatosis, celiac lymph node and hepatic metastasis in the IP+ patients were significantly lower than in the IP- patients. Patients with curative resection, a histological type other than mucinous adenocarcinoma and signet ring cell carcinoma, low and undifferentiated tumor grade, lymph node metastasis, and T3 and T4a benefited from adjuvant IPC. The toxicities were the same except for more patients with leukopenia in the IP+ group (p = 0.001). The number of cycles of IPC and the time of IPC start after surgery had an impact on overall and disease-free survival.
Adjuvant IPC for resectable gastric cancer gave encouraging results and large multicenter prospective randomized controlled studies are warranted.
[Show abstract][Hide abstract] ABSTRACT: Previous research has shown that irradiated splenocytes preserve the antitumor effect and induce relatively weaker graft-versus-host disease in parent C57BL/6~CB6F1 transplantation. The present study was designed to investigate the antitumor effect of 5-Gy-irradiated haploidentical donor leukocyte infusions (DLI) without prior bone marrow transplantation and the possibly involved mechanism in (H-2d/k)~(H-2b/d) infusion model systems.
Hepa 1-6 tumor-bearing mice were used to evaluate the antitumor effect and the possible mechanism of irradiated haploidentical DLI treatment. Changes in tumor volume, lymphocyte proliferation and cytotoxicity, IFN-gamma and IL-2 secretion and donor cell survival in vivo were analyzed.
After irradiated haploidentical DLI treatment of the poorly immunogeneic Hepa 1-6 tumor mouse model, the donor cells were rejected and disappeared within 4 days. Surprisingly, an antitumor response was still observed. The infusion treatment effectively inhibited tumor growth and prolonged the survival of recipients, and this effect could be enhanced by combined treatment with cyclophosphamide and impaired by deleting donor-derived T cells. Moreover, the infusion treatment increased the levels of type 1 cytokines including IFN-gamma and IL-2, and enhanced the proliferation of lymphocyte subsets, particularly CD8 + T and NK cells. Specifically, multiple infusions proved to enhance the antitumor effect without inducing graft-versus-host disease.
As an adoptive therapy, irradiated haploidentical DLI without bone marrow transplantation might be a promising and safe treatment for cancer.
[Show abstract][Hide abstract] ABSTRACT: To analyze the characteristics of serum proteins mass spectra in healthy controls, benign breast tumors, and CA15-3 negative or CA15-3 positive breast cancer patients by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS).
Tissue samples of 113 cases of breast cancer (93 case of CA15-3 negative, 20 case of CA15-3 positive), 103 cases of benign breast tumor and 92 cases of healthy controls were examined and analyzed by SELDI and protein chip (CM10) techniques. Biomarker Pattern Software (BPS) was used to detect the protein peaks significantly different between them and establish a diagnostic pattern which was further evaluated by a blind test.
Twelve significantly different protein peaks were found in serum samples between breast cancer patients and healthy controls. Eleven significantly different peaks were found between benign breast tumor patients and healthy controls. By combined analysis of those three different protein mass spectra, the peak 15 952 was found to be significantly different between breast cancer group and healthy controls, and the peak 7985 was significantly different among breast cancer group, benign breast tumor group and health controls. The blind test with the differential proteins for the serum samples of 93 cases of CA15-3 negative breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 80.6% and specificity was 91.7%. The blind test in 20 cases of CA15-3 positive breast cancer and 36 cases of benign breast tumors showed that the sensitivity was 75.0% and specificity was 91.7%. Four significantly different protein peaks were found between the benign breast tumor patients and CA15-3 negative breast cancer patients. No significantly different protein were found between CA15-3 negative and CA15-3 positive patients.
Significantly different protein peaks can be screened out in breast cancer, benign breast tumor patients and healthy controls by SELDI-TOF-MS analysis.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 09/2010; 32(9):698-702.
[Show abstract][Hide abstract] ABSTRACT: Cytokine-induced killer (CIK) cells have high anti-tumor activity for hepatocellular carcinoma (HCC). Whether CIK cell therapy can eradicate residual cancer cells and prevent or postpone tumor relapse after transcatheter arterial chemoembolization (TACE) should be testified. This study was to evaluate the efficacy of CIK cell therapy combined with TACE on HCC.
A total of 146 consecutive patients with unresectable HCC were divided into combination group (72 patients treated with CIK cell therapy combined with TACE) and TACE group (74 patients treated only with TACE). The progression-free survival (PFS) and overall survival (OS) were analyzed.
The 6-month, 1-year, and 2-year PFS rates were 72.2%, 40.4%, 25.3% in combination group, and 34.8%, 7.7%, 2.6% in TACE group. The median time to progression was 11 months [95% confidence interval (CI), 8-14 months] in combination group and 5 months (95% CI, 4-7 months) in TACE group. The estimated 6-month, 1-year, and 2-year OS rates were 90.3%, 71.9%, 62.4% in combination group, and 74.6%, 42.8%, 18.8% in TACE group. The median OS was 31 months (95% CI, 27-35 months) in combination group and 10 months (95% CI, 7-13 months) in TACE group. The times of TACE, ECOG performance status, and CIK cell therapy were independent prognostic factors for PFS and OS.
Adjuvant immunotherapy with CIK cells could greatly improve the efficacy of TACE on HCC, and plays an important role in prolonging the PFS and OS of HCC patients after TACE.
[Show abstract][Hide abstract] ABSTRACT: Renal-cell carcinoma (RCC) is susceptible to immune therapy including the use of the nonmyeloablative allogeneic transplantation (NST). However, NST can produce severe toxicity, might not be appropriate for many patients with metastatic RCC. Other novel allogeneic immunotherapies are designed to induce an autologous immune response directed against the malignancy. In single-arm phase II trials, thalidomide has demonstrated a modest activity in the treatment of advanced RCC. Here we present a case report in which a patient with advanced RCC in the absence of transplant conditioning, that was receiving thalidomide, was infused with partially HLA-matched irradiated allogeneic lymphocytes. In this patient a complete response with weak acute graft-versus-host disease (GVHD) was observed. No evidence of the disease was present over the subsequent 36 months survival of the patient, suggesting that the infusions may have played a major role in the antineoplastic effect. A potential mechanism of this protocol may involve a host-versus-graft reactions-mediated antitumor effect against the malignancy. In addition, the present results suggest that a combination protocol with alternate treatment (e.g., chemotherapy) schedules merit further investigation in the management of various malignancies.
Medical Oncology 07/2009; 27(2):554-8. · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Aims: To investigate the efficacy and safety of a gemcitabine plus oxaliplatin combination regimen and a floxuridine plus oxaliplatin combination regimen used in transcatheter arterial chemoembolization for patients with inoperable hepatocellular carcinoma (HCC).Methods: From October 2005 to October 2008, 122 chemonaïve patients with newly diagnosed, inoperable HCC were randomized into a gemcitabine plus oxaliplatin combination regimen group (GO group) or a floxuridine plus oxaliplatin combination regimen group (FO group). The GO group was treated with 1,600 mg of gemcitabine and 200 mg of oxaliplatin, and the FO group was treated with 1,000 mg of floxuridine and 200 mg of oxaliplatin. Both groups were treated with glutin and iodolipol as the embolic agent in the transcatheter arterial chemoembolization (TACE).Results: The progression-free survival, the median survival period, and the median time to progress had no significant difference between the two groups. However, there was a significant difference in the incidence of grade 3/4 thrombocytopenia between the two groups (P = 0.002). Grade 3/4 hematologic toxicity was observed only in the GO group. One patient (1.7%) with grade 3/4 leukopenia and 6 patients (10%) with grade 3/4 thrombocytopenia were observed. A multivariate analysis revealed that the Eastern Cooperative Oncology Group (ECOG) scores and portal vein thrombosis were the only independent prognostic factors that affected progression-free survival.Conclusions: The floxuridine plus oxaliplatin combination regimen was tolerated better than the gemcitabine plus oxaliplatin combination regimen used in TACE.
[Show abstract][Hide abstract] ABSTRACT: Platinum-based chemotherapy regimens are often recommended for patients with unresectable thymic carcinoma. In more than 60 cases, however, the systemic chemotherapy provides little benefit. In this report, we described a case of advanced KIT- and VEGF-positive thymic carcinoma with liver and lung metastasis. The patient, a 46-year-old man, exhibited a resistance to cisplatin-based chemotherapy, but responded to the treatment with sorafenib, a molecular target-based therapy. After 4 months of sorafenib therapy, his lung and liver metastases as well as the mediastinal tumor shrank dramatically. Moreover, the tumors showed stable disease for at least 9 months. To the best of our knowledge, it is the first report about a response of advanced thymic carcinoma to sorafenib. The preliminary study suggested that molecular target-based therapy could be an alternative treatment to those chemotherapy-refractory patients.
Medical Oncology 11/2008; 26(2):157-60. · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the expression of soluble MICA (sMICA) in serum of patients with breast tumor, and explore the roles of sMICA in immune escape.
ELISA was used to examine the sMICA in peripheral blood. The expression of NKG2D were identified by Flow cytometry. The cytotoxicity of NK cells to breast cancer cells was observed with MTT assay.
sMICA was not detected in the serum of healthy person, but(76.8+/-22.3) ng/L in breast benign tumor patients and (205.4+/-71.3) ng/L in breast malignant tumor patients. There was positive correlation between sMICA levels and breast cancer stage. After incubation with sMICA, NK cells got decrease in cytotoxicity from (76.2+/-6.7) % to (48.4+/-4.1) % .The expression of NKG2D and secretion of IFN-gamma decreased at the same time. IL-15 up-regulated the expression of NKG2D on NK cells and increased NK cells cytotoxicity to breast cancer cells.
sMICA level is positive correlated with breast cancer TNM stage. sMICA reduced the expression of NKG2D, impaired NK-mediated immune surveillance and led to immune escape of breast tumor. IL-15 could up-regulate the expression of NKG2D and increase NK cells cytotoxicity.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 10/2008; 24(9):904-7.
[Show abstract][Hide abstract] ABSTRACT: To explore the clinical significance of detection of cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA expression in the diagnosis of micrometastasis in the peripheral blood of patients with breast cancer, and the relationship with other clinicopathological characteristics.
Peripheral blood samples were collected from 28 normal female healthy volunteers, 20 patients with benign breast disease, and 108 patients with breast cancer (88 had undergone operation and 20 with metastasis). Real-time quantitative PCR was used to detect the mRNA expression of CK19 and CEA in the peripheral blood.
mRNA expression was negative in the blood samples from the 28 normal volunteers for both CK19 and CEA. None of the 20 patients with benign breast disease was positive for CEA mRNA, but one was positive for CK19 mRNA (5%). Of the 108 patients with breast cancer, 26 (24.1%) were positive for CK19 mRNA, 23 (21.3%) were positive for CEA mRNA, and 15 (13.9%) were positive for both CK19 mRNA and CEA mRNA. The positive rates of CK19 mRNA and/or CEA mRNA of the metastatic breast cancer patients were higher than those of the operable breast cancer patients. Statistically significant differences in tumor size, clinical stage, and expression levels of k(i)67, variant exon 6 containing isoforms of CD44 (CD44v6), and vascular endothelial growth factor (VEGF) were found between the operable breast cancer patients with micrometastasis in peripheral blood and the patients without micrometastasis (all P < 0.05). And there was no statistically significant difference between the two groups in age, tumor location, pathological histological type, nodal metastasis, and expression levels of estrogen receptor (ER), pregnant receptor (PR), CerbB2, and matrix metalloproteinase-9 (MMP9) (all P > 0.05). Multivariate analysis showed that tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF were associated with micrometastasis in peripheral blood.
The combined detection of CK19 and CEA mRNA raises the detection rate of micrometastasis in the peripheral blood of breast cancer patients. Tumor size, clinical stage, expressions of ki67, CD44v6, and VEGF are effective predictors of micrometastasis in the peripheral blood of breast cancer patients.