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1: Int J Gynecol Cancer. 2006 Jan-Feb;16(1):156-64. Impact Factor: 1.147 Procaspase-3 enhances the in vitro effect of cytosine deaminase-thymidine kinase disuicide gene therapy on human ovarian cancer. Song Y, Kong B, Ma D, Qu X, Jiang S. Departments of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, P.R. China. Because the efficacy of genetic prodrug activation therapy (GPAT) using herpes simplex virus thymidine kinase (tk)/ganciclovir (GCV) or Escherichia coli cytosine deaminase (cd)/5-fluorocytosine (5-FC) is not satisfied in early clinical trials and the mechanism of both the GPATs have been shown to lead to the activation of cell apoptotic pathway, we hypothesized that coexpression of procaspase-3, a central downstream executioner of apoptotic pathways, with cd-tk gene leads to enhanced cell death in ovarian cancer cells in vitro. Following
transfection with the vectors encoding cd and tk, 5-FC and GCV treatments lead
to greater cell death in procaspase-3-expressing clones of 3AO (3AO-caspase-3)
than control cells (3AO-pcDNA3), as well as more rapid activation of caspase-3
and more rapid cleavage of poly (adenosine diphosphate-ribose) polymerase
(PARP). There is a greater degree of cell apoptotic rate in the
procaspase-3-expressing clones than in control cells following the treatment
with cd-tk/5-FC + GCV, and apoptosis is the main cell death form. None of these
effects is seen following transfection with a control vector that does not
encode tk and cd (pBTdel-279). The results strongly suggest that coexpression of
procaspase-3 may lead to a significant enhancement of the efficacy of cd-tk/5-FC
+ GCV, and this strategy would be a novel and promising approach for the
treatment of ovarian cancer.
PMID: 16445627 [PubMed - in process]
2: Gynecol Oncol. 2006 Jan 3; [Epub ahead of print]
Impact factor of this journal
2004: 2.083
Biomarker discovery for ovarian cancer using SELDI-TOF-MS.
Zhang H, Kong B, Qu X, Jia L, Deng B, Yang Q.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University,
Ji'nan 250012, Shandong Province, P.R. China.
OBJECTIVES.: The purpose of this study is to discover potential biomarkers for
the detection and monitoring of adjuvant chemotherapy for ovarian cancer.
METHODS.: Serum samples from ovarian cancers and non-cancer controls were
analyzed using surface-enhanced laser desorption/ionization time-of-flight mass
spectrometry (SELDI-TOF-MS). To discover the possible diagnostic biomarker for
ovarian cancer, a preliminary training set of spectra derived from 31 primary
ovarian cancer patients, 16 patients with benign ovarian diseases, and 25
healthy women was used to develop a proteomic model that discriminated cancer
from non-cancer effectively. A blind test set, including 43 new cases, was used
to validate the sensitivity and specificity of this multivariate model. To
explore treatment-induced serum protein change, the protein profiles generated
from 16 postoperative patients before chemotherapy are compared with those
obtained after chemotherapy. RESULTS.: A Four-peak model was established in the
training set that discriminated cancer from non-cancer with sensitivity of 90.8%
and specificity of 93.5%. A sensitivity of 87.0% and a specificity of 95.0% for
the blind test were obtained, compared with 60.7%, 55% for CA125 for the same
samples. These 4 markers performed significantly better than the current
standard marker, CA125 (P < 0.05). One protein peak (mass/charge ratio [m/z],
4475) was identified in 12 of 16 (75%) postoperative patients after
chemotherapy, but was absent before chemotherapy. CONCLUSION.: The proteins
represented by these peaks are candidate biomarkers for ovarian cancer diagnosis
and/or monitoring treatment response.
PMID: 16403569 [PubMed - as supplied by publisher]
3: Immunol Cell Biol. 2005 Dec;83(6):668-73.
Impact Factor: 2.618
Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic
cells.
Qu X, Yang MX, Kong BH, Qi L, Lam QL, Yan S, Li P, Zhang M, Lu L.
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan,
China.
Hypoxia, a prominent characteristic of inflammatory tissue lesions and solid
tumour microenvironments, is a crucial stimulus capable of modulating the
expression of specific genes involved in leucocyte recruitment. Although studies
have shown that hypoxia can affect leucocyte migration by influencing the
expression of migration-related genes, such as matrix metalloproteinases (MMP)
and their endogenous tissue inhibitors of matrix metalloproteinases (TIMP), it
remains unclear whether hypoxia can affect the migration of dendritic cells
(DC). In this study, we showed that human monocyte-derived DC under hypoxic
conditions in a transwell system have significantly reduced migratory capacity
compared to normoxic controls. A moderate phenotypic change of hypoxic DC was
observed. In hypoxic DC, we detected a twofold increase in TIMP-1 transcript
levels, and downregulated expression of MMP-9 and membrane type 1-MMP genes by
threefold and 17-fold, respectively. Our results suggest that hypoxia may
inhibit DC migratory activity by regulating the balance between MMP and TIMP
gene expression.
PMID: 16266319 [PubMed - indexed for MEDLINE]
4: Biochem Biophys Res Commun. 2005 Nov 11;337(1):127-32.
Impact factor of this journal
2004: 2.904
Phototoxicity of Hemoporfin to ovarian cancer.
Song K, Kong B, Qu X, Li L, Yang Q.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University,
Ji'nan 250012, Shandong, PR China.
Hematoporphyrin monomethyl ether (Hemoporfin) is a novel porphyrin-related
photosensitizer. Photocytotoxic effect of Hemoporfin to ovarian cancer is still
unclear. We used human epithelial ovarian carcinoma cell line SKOV3 and its
xenograft model in nude mice to investigate the Hemoporfin-based photodynamic
therapy (PDT) for ovarian cancer. The growth rates of SKOV3 cells were
determined by MTT assays. Flow cytometry combined with dual Annexin V/PI
staining was used to identify the death mode of the cells following PDT. We
demonstrated that Hemoprofin-based PDT induced significant cell death via direct
necrosis induction, and the photocytotoxity to SKOV3 cells is dose related. With
SKOV3 xenograft model in nude mouse, we further demonstrated that
Hemoporfin-based PDT is effective for controlling the tumor growth. Our results
suggest that Hemoporfin is a promising novel photosensitizer for the treatment
of ovarian cancer and merit further evaluation in the clinical practice.
PMID: 16182254 [PubMed - indexed for MEDLINE]
5: Int J Gynecol Cancer. 2005 Sep-Oct;15(5):872-7.
Impact Factor: 1.147
Arsenic trioxide induces apoptosis in cisplatin-sensitive and -resistant ovarian
cancer cell lines.
Kong B, Huang S, Wang W, Ma D, Qu X, Jiang J, Yang X, Zhang Y, Wang B, Cui B,
Yang Q.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University,
Ji'nan, People's Republic of China. kongbeihua@yahoo.com.cn
Arsenic trioxide (As(2)O(3)), has been used for centuries in traditional Chinese
medicine; it has considerable efficacy in the treatment of relapsed acute
promyelocytic leukemia, inducing partial differentiation and promoting apoptosis
of malignant promyelocytes. Although a number of studies have demonstrated that
As(2)O(3) has potent activity against cell growth in a series of leukemia cell
lines, little information is available regarding this compound's effect on cell
growth in solid tumor cell lines. In this study, we investigated the effects of
As(2)O(3)in vitro on ovarian cancer cell lines sensitive (3AO) and resistant
(3AO/CDDP) to cisplatin. The
3-(4,5-dimethy-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to
evaluate cytotoxicity. Flow cytometric analysis was used to determine the
apoptosis, cell cycle distribution. We clearly demonstrated that As(2)O(3)
induced cell apoptosis and inhibition of cell growth in both the cell lines.
Furthermore, we identified that As(2)O(3)-induced apoptosis involved Fas
pathway. As(2)O(3) is an active agent against ovarian cancer cells and could be
effective in the clinical treatment of ovarian cancer.
PMID: 16174238 [PubMed - indexed for MEDLINE]
6: J Chemother. 2005 Jun;17(3):302-8.
Impact Factor: 1.104
High dose chemotherapy and transplantation of hematopoietic progenitors from
murine D3 embryonic stem cells.
Jiang J, Kong B, Shen B, Li L, Yang X, Hou H, Shi Q, Ma D, Ma X.
Qilu Hospital, Shandong University, Jinan, China.
Differentiating embryonic stem (ES) cells are an increasingly important source
of hematopoietic progenitors, useful for both basic research and clinical
applications. To date, characteristics of specific factors capable of
influencing hematopoietic cell fate from ES cells remains elusive. We report
that mMSC Feeder Layer and the combination of VEGF, SCF and TPO strongly promote
hematopoietic differentiation. The results showed that the cells induced from
ES-D3 expressed hematopoietic progenitor antigens (CD34 and CD117), myelocyte
cell antigen (CD11b), erythrocyte cell antigen (Ter119), and transcription
factors (Flk-1, GATA-2, SCL, beta-H1 and beta-major). Furthermore, those induced
differentiated cells were injected into female C57BL/6 mice which were treated
with high dose topotecan chemotherapy to restore part of their blood system
function. We observed rapid white blood cell recovery, which suggested that the
infusion of differentiated cells has a positive impact on hematopoiesis. The Sry
gene in peripheral blood, bone marrow and spleen of transplanted female mice was
confirmed by PCR analysis, which affirmed the existence of the chimera.
PMID: 16038524 [PubMed - indexed for MEDLINE]
7: In Vivo. 2003 Mar-Apr;17(2):153-6.
Impact Factor: 0.811
Efficacy of lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide
gene therapy for ovarian cancer.
Kong B, Wang W, Liu C, Song L, Ma D, Qu X, Jiang J, Yang X, Zhang Y, Wang B, Wei
MQ, Yang Q.
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University,
Jinan 250012, P.R. China. kongbeihua@yahoo.com.cn
Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into
tumor cells using virus-based vectors in conjunction with ganciclovir (GCV)
exposure provides a potential gene therapy strategy for the treatment of cancer.
Effective gene therapy depends on the efficient transfer and specific targeting
of therapeutic genes and their protein products to target cells. The purpose of
this study was to investigate the anti-tumor effect of Lentivirus-mediated and
MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse
models were generated with intraperitoneal injection of human epithelial ovarian
cancer cells 3AO, which are MUC1-positive, HIV-1-based lentiviral vectors
carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected
intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK, followed by
GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or
VP22-TK with GCV inhibited the proliferation and prolonged survival times
compared with the control vector. The survival time of animals treated with
scFv-VP22-TK/GCV was significantly longer than that of animals treated with
VP22-TK/GCV (p = 0.006). CONCLUSION: Our results suggest that MUC1
antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit
ovarian tumor growth and increase survival in a nude mouse model of ovarian
carcinoma. These data support the development of this method for human clinical
trials.
PMID: 12792977 [PubMed - indexed for MEDLINE]
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