ABSTRACT
Objective To investigate the relationship between the expression of inhibition of apoptosis proteins like p53,survivin,bcl-2 and chemosensitivities in gastrointestinal tract carcinomas.Methods The expression of p53,survivin and bcl-2 were determined immunohjstochemically,and the chemosenisitivities to 9 drugs was measured by MTT assay in 84 tissue specimens of gastrointestinal carcinomas.Resuits Positive immunostainning for p53,survivin and bcl-2 were found in 64%,89%and 61%of cases.respectively.Correlation existed between the expression of Sllrvivin and bcl-2(r=0.3027,P＜0.05).In terms of relationship between expression of p53,survivin or bcl-2 and inhibition rates of tumor cells.the inhibition rates to PTX and DDP in p53 strong expression group were lower than those in weak group(t=2.1282,P:0.0363;t=3.8850,P=0.0002).When survivin expressed strongly,the inhibition rates for VCR and DDP decreased significantly(t=2.1693,P=0.0329;t=2.0247,P=0.0046),while that for OXA increased(t=-2.9070,P:0.0047).here were lower tumor inhibition rates for 5-FU.VCR,eADM and OXA in bcl-2 strong expression group than those in weak group(t=2.1483～3.2330,P=0.0347～0.0018,respectively).Conclusions The extent of the expression of P53.survivin or bcl-2 in gastrointestinal carcinomas was associated with the chemosensitivities of some drugs.In assessing the influence of p53,survivin or bcl-2 on durg resistance,many factors and mechanisms should be considered.
ABSTRACT
Objective To investigate the relationship between expression of P-glycoprotein (P-gp), glutathione S-transferase-π (GST-π) and chemosensitivities in lymph node metastases (LNMs) of gastrointestinal carcinomas. Methods Tumor chemosesitivities to 9 drugs was measured by MTT assay, and the expression of P-gp and GST-π were determined immunohistochemically in primary tumor (PT) and LNMs of gastrointestinal carcinomas in 54 patients. Results The P-gp expression was detected in 22% cases (k= -0.0133, P =0.8698) for beth PT and LNMs, and of GST-π in 50% (k =0. 1137, P= 0. 1496). Expression of P-gp and GST-π in LNMs were stronger eompared with PT (Z = -3. 0448, Z = -2. 1178, both P <0. 05). The inhibition rates of LNMs cells for VCR, OPT, OXA, DDP and MTX were lower than those to PT (all P < 0. 05), but for VP-16 it was higher (P < 0. 05). In PT, there were negative correlation between expression of P-gp and inhibition rates of tumor cells for 5-FU, VCR and PTX respectively (r = -0. 4142 ～ -0. 5712, all P <0. 05), and GST-π for 5-FU, VCR, OPT and PTX as well (r = -0. 3927 ～ -0. 4951, all P <0. 05). In LNMs, negative correlation between expression of P-gp and inhibition rates of tumor cells for VP-16, PTX and eADM were found statistically (r = - 0. 3802 ～ - 0. 4624, all P < 0. 05), and also GST-π for 5-FU, VCR and DDP (r = - 0. 3996 ～ - 0. 5345, all P < 0. 05). Conclusions The LNMs of gastrointestinal carcinomas are heterogeneous with respect to expression of mdr-related factors and response to chemotherapy, and more resistant than the PT for chemotherapeutants. Effective adjuvant chemotherapy in gastrointestinal cancers depends on targeting the metastatic component of the tumor.
ABSTRACT
Objective To investigate the relationship between expression of cyclooxygenase-2 (COX-2), Bcl-2 and chemosensitivities in lymph node metastases (LNMs) of gastric carcinoma. Methods The chemosenisitivities to 9 drugs were measured by MTT assay, and the expression of COX-2, Bcl-2 was determined immunohistochemically in 40 paired primary tumor (PT) and lymph node metastases(LNMs)of gastric carcinoma. Results The positive rate of COX-2 and Bcl-2 in PT were 52.5%, 45.0% respectively, and in LNMs, the positive rate were 72.5% and 60.0%. The expression of COX-2 was higher in LNMs than in PT(χ~2=4, P<0.05). There was no statistically difference in the expression of Bcl-2 between PT and LNMs(χ~2=3, P>0.05). There was positive correlation of COX-2, Bcl-2 between PT and LNMs(r=0.3403, 0.4560, beth P<0.05). There was positive correlation between COX-2 and Bcl-2 in PT and LNMs (r=0.6014, 0.5330, both P<0.01). In PT the inhibition rate for 5-FU, VCR and eADM in COX-2 high expression group were lower than those in low expression group (t=2.29, 2.18, 2.41, all P< 0.05). The inhibition rate to 5-FU, PTX and eADM was significantly lower for the Bcl-2 high expression group in PT (t=2.46, 2.23, 2.22, all P<0.05). In LNMs, there were lower inhibition rates for VCR and MTX in COX-2 strong expression group (t=2.17, 2.35, both P<0.05); the inhibition rates to 5-FU, VP-16, PTX and MTX were significantly lower for the Bcl-2 strong expression group in LNMs (t=2.32, 2.29, 2.50, 2.25, all P<0.05). Conclusions COX-2 and Bcl-2 are involved in MDR of gastric carcinoma. The LNMs of gastric carcinoma are heterogeneous with respect to expression of COX-2, Bcl-2 and response to chemosensitivities. Effective adjuvant chemotherapy in gastric carcinoma depends on targeting the metastatic component of the tumor.