Gastric Cancer
Clin Cancer Res. 2006 Jun 15;12(12):3803-13. Dis Markers. 2006;22(3):103-9. Brain
Behav Immun. 2006
Mar 28; [Epub ahead of print]
Carcinoembryonic Antigen-Targeted Selective Gene Therapy for
Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors.
Tanaka
T, Huang
J, Hirai
S, Kuroki
M, Kuroki
M, Watanabe
N, Tomihara K, Kato
K, Hamada
H.
Authors' Affiliations: Departments of Molecular Medicine and Clinical
Laboratory Medicine, Sapporo Medical University, Sapporo, Japan and
Departments of Surgery I and Biochemistry, School of Medicine, Fukuoka
University, Fukuoka, Japan.
PURPOSE: A major problem when using the adenoviral vectors for gene therapy
applications is thought to be related to low transduction efficiency in
cancer cells or to side effects in normal cells. There is an urgent
requirement to improve the specificity of gene delivery in the context of
cancer gene therapy. EXPERIMENTAL DESIGN: We constructed a genetically
modified adenovirus incorporating an IgG Fc-binding motif from the Staphylococcus protein A,
Z33, within the HI loop (Adv-FZ33). A remarkable degree of targeted gene
delivery to gastric cancer cells was obtained with Adv-FZ33 with the fully
human anti-carcinoembryonic antigen (CEA)
monoclonal antibody, C2-45. RESULTS: In vitro LacZ
or EGFP gene expression after Adv-FZ33 infection via C2-45 was 20 times
higher than control monoclonal antibody in MKN-45 at
1,000 viral particles/cell. We generated Ax3CAUP-FZ33 (UP-FZ33),
which is an Adv-FZ33 derivative vector expressing a therapeutic gene (i.e.,
Escherichia coli uracil phosphoribosyltransferase),
which converts 5-fluorouracil (5-FU) directly to 5-fluoro-UMP. UP-FZ33 with
C2-45 enhanced the cytotoxicity of 5-FU by
10.5-fold in terms of IC(50) against MKN-45
compared with control IgG4. In a nude mouse peritoneal dissemination model,
tumor growth in mice treated with UP-FZ33/C2-45/5-FU was significantly
suppressed, and tumor volumes were less than one-fourth of those of the
control IgG4 group (P < 0.05). The median survival time of the
UP-FZ33/C2-45/5-FU group was significantly longer than those treated with
PBS or 5-FU only (P < 0.01). CONCLUSIONS: These data suggest that
CEA-targeted FZ33 mutant adenovirus-mediated gene delivery offers a strong
and selective therapeutic modality against CEA-producing cancers.
PMID: 16778108 [PubMed - in process]
Molecular detection of disseminated tumor
cells in the peripheral blood of patients with gastric cancer: Evaluation
of their prognostic significance.
Wu
CH, Lin
SR, Hsieh
JS, Chen
FM, Lu
CY, Yu
FJ, Cheng
TL, Huang
TJ, Huang
SY, Wang
JY.
Early detection of disseminated tumor cells in the peripheral blood of
patients with early stage gastric cancer could help to improve the outcome
after tumor resection. The aim of this study is to evaluate the prognostic
significance of tumor-related mRNA for the detection of circulating tumor
cells in gastric cancer patients by a reverse-transcriptase polymerase
chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase
reverse transcriptase (hTERT), cytokeratin-19
(CK-19), cytokeratin-20 (CK-20) and carcinoembryonic
antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42
gastric cancer patients and 30 healthy individuals. Additionally, analyses
were carried out for the correlation of these four molecular markers with
patients' clinicopathologic features, as well as
the occurrence of postoperative recurrence/metastasis. Among 42 gastric
cancer patients, the prevalence of mRNA for hTERT,
CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and
78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either
CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated
with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor
invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage
(p<0.001). In addition, the multivariate logistic regression
demonstrated that CEA mRNA expression was an independent and significant
predictor for postoperative recurrence/metastasis (p=0.032). Our findings
suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating
cancer cells in gastric cancer patients' peripheral blood. Patients with
positive CEA mRNA expression in peripheral blood have a significantly
higher risk of postoperative recurrence/metastasis.
PMID: 16788243 [PubMed - in process]
Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP-1alpha gene expression
during tissue healing in non-human primates.
Kalin NH, Shelton
SE, Engeland CG, Haraldsson HM, Marucha PT.
Department of Psychiatry, University of Wisconsin, Madison, WI 53719, USA;
Department of Psychology, University of Wisconsin, Madison, WI 53719, USA.
Stress impairs healing and in part this effect is thought to be mediated by
glucocorticoids. However, the brain systems that
underlie the effects of stress on healing remain to be determined. Since
the central nucleus of the amygdala (CeA) plays a role in mediating an individual's
behavioral and physiological reactivity to stress, we investigated, in
rhesus monkeys, whether selective lesions of the CeA
altered the gene expression of chemokines (IL-8
and MIP-1alpha) that are associated with early dermal healing. We used
rhesus monkeys because they provide an excellent animal model to
investigate brain mechanisms relevant to human stress, anxiety, and
psychopathology. Hypothalamic-pituitary-adrenal (HPA) activity was assessed
in the monkeys prior to the wound healing experiment demonstrating that the
CeA lesions reduce HPA activity. In the healing
experiment, stress decreased IL-8 and MIP-1alpha gene expression in both CeA lesioned and non-lesioned animals. Conversely, the CeA
lesions increased the tissue expression of IL-8 and MIP-1alpha mRNA prior
to and after stress exposure. These results demonstrate that in primates
the CeA is a key brain region involved in the
regulation of processes associated with wound healing. Because of brain and
behavioral similarities between rhesus monkeys and humans, these results
are particularly relevant to understanding brain mechanisms that influence
healing in humans.
PMID: 16574374 [PubMed - as supplied by
publisher]