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The Combined Use Of Celecoxib And Long-acting Lanreotide In Human Gastric Cancer And Its Mechanism Of Action

Posted on:2008-04-07Degree:MasterType:Thesis
Country:ChinaCandidate:R Y J CiFull Text:PDF
GTID:2144360218460148Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background & aimsGastric caner is one of the most common malignant tumors in the world, with its mortality rate ranking the second among the various tumors. It is also the most common malignant tumor in our country, with no obvious decrease of its mortality rate over the years. Neither surgery nor chemotherapy showed satisfactory benefit to patients with gastric cancer but brought severe adverse reaction. Cellular immune in gastric cancer patients plays a significant role in preventing and inhibiting the tumor. It is essential to remove tumor with surgery. However; surgery itself inhibits immunity to some degree. The postoperation chemotherapy may aggravate the inhibition of immunity and may promote the metastasis and recurrence of tumors.Non-toxic drugs are literally called so in comparison to toxic drugs, including growth factor, vitamin, hormone, hormone antagonist, clooxygenase inhibitors, and so on. Over expression of COX is closely related to generation and development of gastric cancer. Somatosatin (SST), derived from the nervous system and gastrointestinal tract, can inhibit tumor. Somatostatin analogs (SSTA) are involved in inhibiting various tumors growth. Our early studies, in vivo and in vitro, showed that COX-2inhibitors and SSTA could synergistically inhibit the growth of human gastric cancer.This study is aimed to investigate the combined use of COX-2inhibitor with SSTA to treat human gastric cancer as well as their mechanism of action.Methods1. Cases collection: forty gastric cancer patients diagnosed by biopsies and status post radical operation from March of 2006 to March of 2007 were collected to investigate.2. Forty gastric cancer patients were randomly divided into 2 Groups: the control group (n=20) and the combined therapy group (n=20).3. Therapeutic regimen before surgery: the patients in control group took no medicine before gastric cancer resection. But the patients in the combined therapy group were treated orally with Celecoxib (0.2g) once per day for 7days and long-acting lanreotide (40mg) injected intramuscularly one time a week before surgery.4. Sample collection: blood samples in combined therapy group before and after taking medicine, and in controlled group before surgery. The resected specimens were fixed by 10%formalin and were prepared with paraffin imbedding.5. The status of tumor necrosis, inflammatory cells infiltration and fibrous tissue proliferation in gastric cancer were examined histologically.6. The micro vessel density(MVD)and the expression of COX—2 in gastric cancer were evaluated by immunohistochemical methods.7. The apoptosis of tumor cells was measured by terminal deoxynucleotidyl transferee—mediated—dUTP nick and labeling.8. T-cell subsets in peripheral blood of gastric cancer patients were studied by using monoclonal antibodies and flow cytometry.Results1. The MVD decreased significantly in combined therapy group compared with that in control group (P<0.05)2. The apoptosis rate in combined therapy group increased significantly compared with that in control group (P<0.05).3. There was no significant difference between two groups on expression of COX-2 protein.4. In combined therapy group, T cell subtype in peripheral blood before and after taking medicine were compared. The number of CD4~+T and CD4~+/CD8~+were increased, while CD8~+T cell was decreased. This tendency is obvious in III-IV stage patients.Conclusions:1. Celecoxib combined with long-acting lanreotide could inhibit the growth of gastric cancer through non-Cox pathway.2. Combined use of Celecoxib and long-acting lanreotide could upregulate the T cellular immune status in gastric cancer patients, especially in III-IV stage patients. 3. Combined use of Celecoxib and long-acting lanreotide does not show obviously advertise reaction but a good tolerance.
Keywords/Search Tags:Stomach neoplasm, Celecoxib, long-acting lanreotide, MVD, Apoptosis, Cellular immune
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