-
[show abstract]
[hide abstract]
ABSTRACT: AIM: Biomarkers have been utilized for prognosis in colorectal cancer, relatively few have been identified. We compared the prognostic value of serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyl transpeptidase (GGT) with carcinoembryonic antigen (CEA) and carbohydrate entigen 19-9 (CA 19-9) in patients with metastatic colorectal cancer (mCRC). METHOD: Blood samples were collected from 239 patients with mCRC presenting between 2005 and 2010 in the Sun Yat-sen University Cancer Center. RESULTS: CEA (p<0.001), CA19-9 (p<0.001), GGT (p<0.001), ALP (p<0.001) and LDH (p=0.001) were statistically significant prognostic factors of overall survival (OS). CEA (p=0.002) and GGT (p=0.021) were validated as independent predictors. On univariate analysis CEA (p=0.003), CA19-9 (p=0.006), GGT (p<0.001) and ALP (p=0.001) were statistically significant predictive factors of progression free survival (PFS) in patients having first-line chemotherapy. CEA (p=0.011) and GGT (p=0.027) were independent. GGT (p=0.001), ALP (p=0.016) and LDH (p=0.039) levels were correlated with the tumour response rate assessed by computerized tomography (CT), while CEA (p=0.724) and CA19-9 (p=0.822) were not. There was a statistically significant difference in OS (p<0.001) and PFS (p<0.001) among patients who had elevations of both CEA and GGT compared with those having only one or neither elevated. CONCLUSION: Among GGT, LDH, and ALP, only GGT plays an independent role with CEA in predicting OS and PFS in mCRC. When coupled with CEA, GGT may lead to improved prognostic predictors. This article is protected by copyright. All rights reserved.
Colorectal Disease 04/2013; · 2.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Elevated activity of the eukaryotic translation initiation factor 4E (eIF4E) plays crucial roles in tumorigenesis and disease progression by disproportionately increasing translation of mRNAs coding proteins that play significant roles in all aspects of malignancy, providing that eIF4E as an attractive target for therapeutic intervention. In this study, we showed that inhibition of eIF4E by small interfering RNAs (siRNA) resulted in cell cycle arrest and suppression of colony formation in MDA-MB-231 triple-negative (TN) breast cancer cells. Migration transwell assay revealed that repression of eIF4E effectively inhibited motility of MDA-MB-231 cancer cells. Importantly, we showed that silencing of eIF4E sensitized MDA-MB-231 cells to chemotherapeutic drugs of cisplatin, adriamycin, paclitaxel and docetaxel as assessed by MTT assay. Moreover, Western blot assay showed that eIF4E siRNA increased Bax/Bcl-2 ratio in MDA-MB-231 cells. Taken together, we showed that knockdown of eIF4E suppressed cell growth and migration, enhanced chemosensitivity, suggesting a potential therapeutic target in TN breast carcinoma.
Medical Oncology 12/2011; 28(4):1302-7. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the utility of Beclin-1 and LC3, two autophagy-related proteins, in predicting the cetuximab efficacy in advanced colorectal cancer (ACRC).
The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1, 2005 to December 31, 2008 were studied, including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression was evaluated by immunohistochemistry, and KRAS status was evaluated by polymerase chain reaction.
Beclin-1 and LC3 expression in ACRC was significantly correlated (r = 0.44, P < 0.01); however, LC3 was more highly expressed in cancerous tissues than in normal tissues (Z = -2.63, P < 0.01). In the cetuximab-containing chemotherapy group, patients with low LC3 expression had higher objective response rates (ORRs) than those with high LC3 expression (52.9% vs 17.9%, P = 0.01), and patients with low Beclin-1 expression had a longer median progression-free survival (PFS) than their counterparts with higher Beclin-1 expression (9.0 mo vs 3.0 mo, P = 0.01). However, neither of these predictive relationships was detected in the group treated with non-cetuximab-containing chemotherapy. Patients with wild-type KRAS had higher ORRs (42.3% vs 9.1%, P = 0.049) and disease control rates (DCRs) (73.1% vs 36.4%, P = 0.035), and longer median PFS (5.5 mo vs 2.5 mo, P = 0.02) than those with mutant KRAS in the cetuximab-containing chemotherapy group. Neither Beclin-1 (P = 0.52) nor LC3 (P = 0.32) expression was significantly correlated with KRAS status.
Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression, and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.
World Journal of Gastroenterology 11/2011; 17(43):4779-86. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The changes in therapeutic strategies were determined and the efficacy of radical mastectomy (RM) and modified radical mastectomy (MRM) on Chinese male breast cancer (MBC) patients was compared. Seventy MBC patients, with a median age of 61 years, were enrolled. The characteristics of MBC were compared in cohort A (1969-1997) and cohort B (1998-2009), and the prognosis was compared between the RM and MRM groups. Infiltrating ductal carcinoma accounted for 81.4% of all cases; 93.7% were estrogen receptor (ER)/progesterone receptor (PR)-positive. More patients in cohort B accepted multidisciplinary treatment, MRM, adjuvant chemotherapy, and endocrine therapy than those in cohort A; however, the 5-year overall survival rates were similar in the two cohorts. The overall survival curves, locoregional recurrence rates, and systematic metastatic rates were similar in the RM and MRM groups. Currently, more MBC patients receive conservative surgery; MRM may be equally effective as RM for MBC.
Breast (Edinburgh, Scotland) 12/2010; 19(6):450-5. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.
Chinese journal of cancer 12/2010; 29(12):1023-8.
-
[show abstract]
[hide abstract]
ABSTRACT: To summarize our experiences with the treatment of non-small cell lung cancer (NSCLC) with cetuximab and compare the therapeutic effects of cetuximab applied in the first line and non-first line settings.
From October 1, 2006 to December 31, 2009, 16 NSCLC patients were treated with cetuximab combined with standard chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy of the therapeutic protocols were analyzed.
A total of 115 cycles of cetuximab treatment were administered in these patients with a median of 6 cycles (7.5 in the first line setting and 2 in non-first line setting). In the 10 patients with cetuximab treatment in the first line setting, the ORR was 40.0% (4/10), DCR was 80.0% (8/10), median TTP was 6.5 months (2-19), and median OS was 8.5 months (2-48); in the non-first line setting, these indices were 33.3% (2/6), 33.3% (2/6), 3.5 months (3-4) and 18 months (4-28), respectively. Both ORR and DCR were similar between the first and non-first line settings (P=0.790, P=0.062). Ten of the patients (62.5%) developed acne-like rash within 3 weeks, who had an ORR of 60% (6/10) and DCR of 90% (9/10); the ORR and DCR in patients without acne-like rash were both 10.4% (1/6), showing no significant difference in ORR (P=0.080) but a significant difference in DCR between the two groups (P=0.003). No treatment-associated death or cetuximab-associated discontinuation occurred. Altogether 11 patients (68.8%) developed acne-like rash, which occurred within 3 weeks in 10 cases. Seven patients showed side effects associated with the chemotherapy.
Cetuximab combined with standard chemotherapy is a good option for Chinese patients with NSCLC and the current data support the application of cetuximab in the first line setting.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 11/2010; 30(11):2423-6.
-
Gui Fang Guo,
Yu Chen Cai,
Bei Zhang,
Rui Hua Xu,
Hui Juan Qiu, Liang Ping Xia,
Wen Qi Jiang,
Pei Li Hu,
Xu Xian Chen,
Fei Fei Zhou,
Fang Wang
[show abstract]
[hide abstract]
ABSTRACT: Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor tissues while its clinical significance was not established, and epidermal growth factor receptor (EGFR) with potential relation to SGLT1 were studied in order to investigate their clinical significance in colorectal cancer (CRC). Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March 1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1) Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher than that in normal tissues. (2) Their expression related with clinical stage (P = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first-line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37 and P = 0.31) had no influence on objective response rate (ORR) and disease control rate (DCR). EGFR overexpression was associated with lower disease-free survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P = 0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was related to higher clinical stages. SGLT1 had a potential impact on the ORR of first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1 did not.
Medical Oncology 11/2010; 28 Suppl 1:S197-203. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cetuximab combined with chemotherapy has been used to treat Non-small cell lung cancer (NSCLC) in recent years, however, the data from China was rare. This study was to summarize our experiences in treating NSCLC patients with cetuximab in the first line setting. From October 1st 2006 to Jun 30th 2010, twelve NSCLC patients were treated with cetuximab combined standard chemotherapy as first line setting in Sun Yat-sen University Cancer Center entered the study and the short-term efficacy and safety were analyzed. A total of 132 cycles of cetuximab treatment, with a median of nine cycles in the whole group were administered. The ORR was 41.7% (5/12), DCR was 83.3% (10/12), median TTP was 5.5 months (2-23), and median OS was 9 months (2-48) in the whole group. There were 75% (9/12) patients occurred acne-like rash within first 3 weeks, their ORR was 55.6% (5/9), DCR was 100% (9/9), however, ORR and DCR in patients who didn't occurred acne-like rash within first 3 weeks were 0 and 33.3% (1/3), the difference ORR between two group was insignificant (P = 0.091), however, DCR was significant different (P = 0.007). There no treatment-associated death and no cetuximab-associated discontinuation. The incidence of acne-like rash was 83.3% (10/12) and 75% (9/12) occurred within first 3 weeks, there were eight patients suffered side effects associated with chemotherapy. So we can draw a conclusion that the short-term outcome of cetuximab application in first line setting for patients with NSCLC were promising since the higher ORR and DCR, especially those occurred acne-like rash within the first 3 weeks, and the addition of cetuximab in this population was safe.
Medical Oncology 10/2010; 28 Suppl 1:S570-6. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the efficacy and safety of cetuximab combined with chemotherapy for patients with advanced colorectal cancer (ACRC) and unclear K-ras status.
Clinical data of 102 ACRC patients, treated by cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to December 2008, were collected. The cumulative survival rate, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) of the cases were calculated. The difference in ORR, DCR, PFS and oval survival (OS) between the regimens used as first-line and non-first-line treatment, and between the regimens including oxaliplatin and irinotecan were compared.
The overall ORR of cetuximab plus chemotherapy was 43.1%, DCR 73.5%, median PFS 4.0 months, OS 28.5 months, and the 1-year, 3-year, and 5-year survival rate was 89.2%, 50.9% and 27.5%, respectively. The differences in ORR (50.0% vs. 40.0%, P = 0.344), DCR (78.1% vs. 72.9%, P = 0.571) and OS (51.0 months vs. 35.0 months, P = 0.396) between the regimens as first line and as non-first line treatment were not statistically significant. However, the PFS of the regimen as first-line was longer than that as non-first-line treatment (PFS 5.5 months vs. 3.0 months, P = 0.001). The differences in ORR (54.2% vs. 40.0%, P = 0.223), DCR (79.2% vs. 74.7%, P = 0.654), PFS (5.0 months vs. 3.0 months, P = 0.726) and OS (36.0 months vs. 40.0 months, P = 0.759) between cetuximab plus oxliplatin and irinotecan were not statistically significant. The most common side effects of cetuximab plus chemotherapy were acneiform eruption (80.4%, grade 3-4 in 9.8%), neutropenia (66.7%, grade 3-4 in 18.6%), and diarrhea (19.6%, grade 3-4 in 5.9%). No treatment-related death was recorded.
Patients with advanced colorectal cancer and unclear K-ras treated by cetuximab combined with chemotherapy have good ORR and OS, and the regimen is safe with less adverse events for them. There is no significant difference between the efficacies of regimens as first line and as non-first line treatment, and between cetuximab plus oxliplatin and cetuximab plus irinotecan regimens.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 10/2010; 32(10):777-81.
-
[show abstract]
[hide abstract]
ABSTRACT: It is not clear if there is a difference in prognosis between male breast cancer (MBC) and female breast cancer (FBC) patients. The aim of this study was to compare the prognosis of MBC and FBC patients in China and the prognosis of MBC and their corresponding postmenopausal FBC patients.
Thirty-five MBC patients who were treated at the Sun Yat-sen University Cancer Center between 1969 and 2004 were enrolled in the study. Seventy FBC patients who were matched with the MBC patients for TNM stage, year of diagnosis, and age at diagnosis were simultaneously enrolled in the study. A second group comprising 18 MBC patients and their corresponding 36 matched postmenopausal FBC patients were also enrolled. The whole group and the postmenopausal groups were compared for five- and ten-year survivals.
All the factors that could potentially affect prognosis were comparable among the groups except more FBC than MBC patients underwent endocrine therapy and a modified radical mastectomy. The 5- and 10-year survivals in the whole group were 81.6% and 60.3% for men and 90.7% and 73.5% for women (P = 0.02). The 5- and 10-year survival in the postmenopausal group was 82.5% and 100% for men and 66.0% and 85.9% for women (P = 0.159).
Chinese FBC patients had a better prognosis than Chinese MBC patients. However, MBC patients and their corresponding postmenopausal FBC patients had a similar prognosis.
Chinese medical journal 09/2010; 123(17):2347-52. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Male breast cancer (MBC) in China usually has been studied retrospectively with small sample size, and studies analyzing the prognostic factors are rare. This study was to investigate the prognostic factors of Chinese patients with MBC based on the data from a single institute with a relatively large sample.
Clinical data of 72 patients with histopathologically confirmed MBC who received treatment at Sun Yat-sen University Cancer Center between January 1969 and March 2009, were collected. Kaplan-Meier, log-rank test and Cox regression model were used for statistical analysis.
The 5-year overall survival rate was 72.4%, and the survival rates for stage I, II, III, and IV were 100%, 74.2%, 57.2%, and 0%, respectively. Univariate analysis showed that the tumor size (P < 0.001), axillary lymph node status (P = 0.001), TNM stage (P = 0.001), operation model (with vs. without: P < 0.001; classic radical resection vs. modified radical resection, P = 0.336) and endocrine therapy(P = 0.02) significantly influenced the survival. Multivariate Cox regression showed that TNM stage (P = 0.035), operation model (P = 0.021) and endocrine therapy (P = 0.019) were independent prognostic factors for MBC.
Early diagnosis and comprehensive treatment strategy consisting of surgery and endocrine treatment is essential to improve the survival of the patients with MBC, and TNM stage, operation and endocrine treatment are the significant prognostic factors for MBC.
Chinese journal of cancer 02/2010; 29(2):184-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Background and Objective: Studies showed that cetuximab combined with chemotherapy was effective on advanced colorectal cancer (ACRC) in recent years, however, few reports based on large case cohort are available in China. This study was to analyze the efficacy of cetuximab combined with chemotherapy for 53 chinese patients with ACRC. Methods: Clinical data of 53 patients with ACRC, treated with cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to April 2008, were analyzed for short-term efficacy and safety. The efficacy of the regimen used as first-line and non-first-line treatment was compared by Chi-square test; the effect of the regimen on prognosis was analyzed by multivariate Cox proportional hazards model. Results: Of the 53 patients with colorectal adenocarcinoma, 40 were men and 13 were women, with a median age of 55 years. A total of 572 weeks (median, 8 weeks) of cetuximab treatment were completed. The overall response rate (RR) of the regimen was 39.6% and the disease control rate 66.0%. The disease control rates were similar when the regimen was used as first-line and non-first-line treatment (80.3% vs. 60.5%, P=0.177). For all 53 patients, clinical stage was an independent prognostic factor (P=0.002, OR>1). The most common Grade 3 to 4 adverse events included acne-like rash (7.5%), neutropenia (18.9%), and diarrhea (5.6%). No hypersensitive reaction or treatment-related death was observed. Only one patient discontinued treatment because of Grade 4 diarrhea and neutopenia. Conclusions: Cetuximab combined with chemotherapy can achieve relatively high disease control rate for ACRC patients, with less adverse events. Whether cetuximab has better effect in first-line treatment than in non-first-line treatment needs further study.
Ai zheng = Aizheng = Chinese journal of cancer 12/2009; 28(12):1317-23.
-
Jin-E Yao,
Min Yan,
Zhong Guan,
Chao-Bin Pan, Liang-Ping Xia,
Chuan-Xing Li,
Li-Hui Wang,
Zi-Jie Long,
Yan Zhao,
Ming-Wei Li,
Fei-Meng Zheng,
Jie Xu,
Dong-Jun Lin,
Quentin Liu
[show abstract]
[hide abstract]
ABSTRACT: The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated.
Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBalpha expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBalpha, these changes were accompanied by nuclear translocation of nuclear factor-kappaB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBalpha reduction was abrogated by suppression of Akt either chemically or genetically.
Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-kappaB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.
Molecular Cancer 11/2009; 8:95. · 3.99 Impact Factor
-
Liang-Ping Xia,
Bei Zhang,
Mao-Zhen Liu,
Pi-Li Hu,
Xu-Xian Chen,
Gui-Fang Guo,
Hui-Juan Qiu,
Yu-Ming Rong,
Sui-Yi Qian,
Fei-Fei Zhou,
Yuan-Yuan Huang,
Tao-Li Wang
[show abstract]
[hide abstract]
ABSTRACT: Cetuximab combined with radiotherapy or chemotherapy has been used to treat head and neck cancer in recent years, but few reports are available in China now. This study was to summarize our experiences in treating patients with head and neck cancer cetuximab.
From October 1st, 2005 to September 30th, 2008, six with patients head and neck cancer were treated using cetuximab combined with radiotherapy and five were treated using cetuximab combined with chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy and safety were analyzed.
A total of 82 cycles of cetuximab treatment, with a median of seven cycles, were administered safely. There was no treatment-associated death and no cetuximab-associated discontinuation. In cetuximab combined with radiotherapy group, four patients achieved complete response (CR) and two achieved partial response (PR); all CR patients had hadacne-like rash (three cases were > or = grade III), only one PR patient had grade I rash; five patients had skin reaction in the irradiation field (four cases of skin reaction were > or = grade III); hematological toxicity was slight excepted one case of grade IV. In cetuximab combined chemotherapy group, two patients achieved PR, two had stable disease (SD) and one had progressed disease (PD); the of acne-like rash was low, and three patients experienced bone marrow depression above grade III.
Cetuximab combined with either radiotherapy or chemotherapy are good options for suitable patients with head and neck cancer.
Ai zheng = Aizheng = Chinese journal of cancer 09/2009; 28(9):977-82.
-
[show abstract]
[hide abstract]
ABSTRACT: Aurora kinases play key roles in the transition of G2/M phase by regulating functions of centrosomes and microtubules. Overexpression of Aurora-A, a new oncogene, can induce centrosome amplification, aneuploidy and tumor formation. Aurora kinases are closely associated with breast cancer. In this article, we reviewed the mechanisms of Aurora kinases inducing tumorigenesis of breast cancer via interacting with p53 gene, BRCA1 gene, PTEN/PI3K/AKT pathway, gene polymorphism, estrogen, and so on, analyzed the expression of Aurora kinases in breast cancer and its relationship with prognosis.
Ai zheng = Aizheng = Chinese journal of cancer 07/2009; 28(6):668-72.
-
[show abstract]
[hide abstract]
ABSTRACT: Isodon diterpenoids have received considerable phytochemical and biological attention for their strong antitumor activity with low toxicity. In this study, ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, was tested on human Hep3B and MDA-MB-453 cell lines and Hep3B xenograft models. The results showed ExcisaninA could inhibit the proliferation of Hep3B and MDA-MB-453 cells via induction of apoptosis, with the evidence of increasing AnnexinV-positive cells and characteristic morphologic changes of apoptosis in the nucleus. Also, ExcisaninA sensitized Hep3B cells to 5-fluorouracil treatment or MDA-MB-453 cells to ADM treatment in vitro. In Hep3B xenograft models, ExcisaninA at 20 mg/kg/d remarkably decreased the xenograft tumor size and induced tumor cells apoptosis using transferase-mediated FITC-12-dUTP nick-end labeling assay. More importantly, we found that ExcisaninA could inhibit AKT activity and block its signal pathway in vitro and in vivo. And treatment with ExcisaninA significantly reduced the number of viable cells in Hep3B/myr-AKT1 cells more than that in control cells. Together, ExcisaninA might be a potent inhibitor of AKT signaling pathway in tumor cells. These data provide validation for the development of ExcisaninA to treat cancers displaying elevated levels of AKT.
Molecular Cancer Therapeutics 05/2009; 8(4):873-82. · 5.23 Impact Factor
-
Xiang-Bo Wan,
Zi-Jie Long,
Min Yan,
Jie Xu, Liang-Ping Xia,
Li Liu,
Yan Zhao,
Xue-Fei Huang,
Xian-Ren Wang,
Xiao-Feng Zhu,
Ming-Huang Hong,
Quentin Liu
[show abstract]
[hide abstract]
ABSTRACT: Mitotic serine/threonine kinase Aurora-A (Aur-A) plays a critical role in regulating centrosome segregation and spindle assemble. Aur-A overexpression causes excessive centrosome duplication and abnormal spindle structure, leading to tumor malignant progression. Here, we investigated Aur-A expression in nasopharyngeal carcinoma (NPC) and the association between Aur-A and NPC invasiveness. We showed that overexpression of Aur-A in tumor tissues was correlated with cranial bone invasion and clinical stage in NPC patients. Suppression of Aur-A by either selective Aurora inhibitory VX-680 or small-interfering RNA caused G(2)/M arrest and apoptotic cell death in NPC CNE-2 cells. Significantly, inhibition of Aur-A suppressed CNE-2 cell invasion and restored membrane expression of epithelial markers, E-cadherin and beta-catenin, suggesting a reversed epithelial-mesenchymal transition process in cancer cells. In addition, we found that Aur-A-regulated epithelial-mesenchymal transition and invasion were mediated by mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, suppression of MAP kinase by small-interfering RNA or its upstream MEK1/2-selective inhibitor U0126 abrogated cell invasion enhanced by Aur-A overexpression. On the other hand, forced overexpression of constitutively active form of MEK1/2, MEK2DD, in CNE-2 cancer cells rescued cell invasive ability suppressed by VX-680-imposed Aur-A inhibition. Our results indicated that Aur-A acted through a downstream MAP kinase pathway to promote epithelial-mesenchymal transition and invasiveness in nasopharyngeal tumorigenesis. Small chemical inhibitor VX-680 may offer as a promising molecular targeting agent in human NPC.
Carcinogenesis 08/2008; 29(10):1930-7. · 5.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tumor markers which relate to cell proliferation and metabolism have seldom been studied in maxillary sinus cancer. This study was conducted to identify the correlation of glutathione S-transferase pi (GST-pi) and proliferating cell nuclear antigen (PCNA) expression to prognosis of advanced maxillary sinus squamous cell carcinoma (SCC).
The expression of GST-pi and PCNA in 54 specimens of maxillary sinus SCC, 29 specimens of benign maxillary tumor, and 20 specimens of normal nasal mucosa was detected by immunohistochemistry. The correlation of GST-pi and PCNA expression to prognosis of advanced maxillary sinus SCC was analyzed by Kaplan-Meier method. The prognosis was analyzed by Cox multivariate model.
The overexpression rates of GST-pi and PCNA were significantly higher in maxillary sinus SCC than in benign maxillary tumor and normal nasal mucosa (74.1% vs. 89.6% and 15.0%, P<0.01; 79.6% vs. 3.4% and 0, P<0.01). The 5-year survival rate was significantly higher in advanced maxillary sinus SCC patients with high expression of GST-pi than in the patients with low expression of GST-pi (34.5% vs. 21.2%, P=0.025); the difference between the patients with high and low expression of PCNA was not significant (18.0% vs. 27.0%, P=0.890). The expression of GST-pi was an independent prognostic factor of advanced maxillary sinus SCC (P=0.039, odds ratio>1).
The overexpression of GST-pi is an independent prognostic factor of advanced maxillary sinus SCC, but that of PCNA isn't.
Ai zheng = Aizheng = Chinese journal of cancer 10/2005; 24(10):1267-71.
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of four types of neck dissections for the recurrent and persistent lymph nodes of NPC after radiotherapy.
The clinical data of 88 cases of nasopharyngeal carcinoma with recurrent and persistent lymph nodes after radiotherapy were analyzed retrospectively, the 5-year survival rate, recurrent rate, distant metastatic rate and surgical complications were analyzed. The survival rate and recurrent rate of the radical neck dissection (RND), modified radical neck dissection (MRND), selective neck dissection (SND) and lymph node resection (LNR) were compared. The survival and recurrent rate between those with and without postoperative radiotherapy were investigated as well.
The 5-year survival rate and recurrent rate of whole group were 42.8% and 22.7%, respectively. As for the patients with disease staged II, III, IV, the 5-year survival rates were 56.7%, 36.1% and 32.4%, respectively. The 5-year survival rate of groups of RND, MRND, SND and LMR were 39.8%, 60.0%, 37.9% and 44.1%, respectively, the differences were insignificant (Log Rank = 1.0, P = 0.8011), the recurrent rate of the lymph node among the 4 groups were insignificant either (chi2 = 0.470, P = 0.493). The 5-year survival rates of those with and without postoperative radiotherapy were 39.1% and 45.3%, respectively, the differences were insignificant (Log Rank = 0.06, P = 0.8138), the recurrent rate of the two groups were insignificant (chi2 = 0.593, P = 0.441).
The four types of neck dissection were effective and safe to control the recurrent and persistent lymph nodes in the neck after radiotherapy, as long as choosing patients rationally and gave postoperative radiotherapy if necessary.
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 03/2005; 40(2):95-9.
-
Gui-Fang Guo,
An-Kui Yang,
Ru-Hua Xie,
Zhi-Hua Chen,
Qiu-Liang Wu,
Shen-Ming Ou,
Wei-Wei Liu, Liang-Ping Xia,
Ming-Yuan Chen,
Jin-Xin Zhang,
Jian-Hui Wu
[show abstract]
[hide abstract]
ABSTRACT: Five-year survival rate of patients with maxillary malignant neoplasms is low, the prognostic factors of these neoplasms were unclear. This study was to investigate prognostic factors of maxillary sinus malignant neoplasms.
Records of 151 inpatients with malignant neoplasms of maxillary sinus initially treated at Cancer Center of Sun Yat-sen University from Sep. 1983 to Mar. 1999 were reviewed. Of 151 cases, 72 were squamous cell carcinoma (SCC), 44 were adenocarcinoma, 16 were sarcoma, and 19 were other histological types; according to 1997 UICC classification, 7 were stage II, 55 were stage III, and 89 were stage IV; 66 patients received combined therapy of surgery and radiotherapy, 14 received surgery alone, 25 received radiotherapy alone, 39 received other treatments, and 7 gave up treatment. All patients were followed up for more than 5 years. Influences of clinicopathologic factors on prognosis of patients with maxillary sinus malignant neoplasms were analyzed by Kaplan-Meier method, and Cox regression model with SPSS10.0 software.
Five-year overall survival rate of patients of </=40 years old was 55.7%, that of patients of >40 years old was 33.3%(P=0.030); that of patients with SCC was 30.2%, of patients with adenocarcinoma was 57.5%, of patients with sarcoma was 24.3%, of patients with tumor of other histological types was 50.7% (P=0.011); that of patients with tumor of stage II, III, and IV were 85.7%, 45.8%, and 32.7%, respectively (P=0.029); that of patients with cervical metastases was 14.4%, of patients without cervical metastases was 44.1% (P=0.005); that of patients with distant metastases was 14.3%, of patients without distant metastases was 41.1% (P=0.011); that of patients without treatment was 14.3%, of patients treated with surgery alone was 42.9%, of patients treated with radiotherapy alone was 32.3%, of patients treated with combined therapy of surgery and radiotherapy was 50.8%, of patients treated with other treatments was 29.1% (P=0.004). Univariate survival analysis showed that the above 6 factors were prognostic factors of patients with maxillary sinus malignant neoplasms. Multivariate analysis showed that combination of surgery and radiotherapy (P=0.004, OR< 1), clinical stage (P=0.025, OR >1), SCC (P=0.016, OR >1), and sarcoma (P=0.003, OR >1) were independent prognostic factors of patients with maxillary sinus malignant neoplasms.
For maxillary sinus malignant neoplasms, patients with SCC or sarcoma had poorer survival than patients with adenocarcinoma or other histological types of tumor; patients with sarcoma had poorer survival than patients with SCC. The higher the patient's clinical stage was, the worse his prognosis was. Combination of surgery and radiotherapy may be the best treatment for patients with maxillary sinus malignant neoplasms.
Ai zheng = Aizheng = Chinese journal of cancer 11/2004; 23(11 Suppl):1546-50.
