TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without recieiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Prognostic value of T lymphocytes infiltration in breast cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.</p><p><b>METHODS</b>Paraffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) .</p><p><b>RESULTS</b>Intraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.</p><p><b>CONCLUSIONS</b>In the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.</p>

Gene expression profiling of nasopharyngeal carcinoma cell line 5-8F-EGFP and the liver metastatic 5-8F-H3B-EGFP cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the gene expression profiles of nasopharyngeal carcinoma (NPC) cell line 5-8F-EGFP and the liver metastatic 5-8F-H3B-EGFP cells.</p><p><b>METHODS</b>The fluorescence-labeled cDNA were prepared separately from the total RNA extracted from the two cell lines and hybridized with Human_U133A2.0 Genechip (Affymetrix, USA) containing approximately 18 400 known gene. The gene expression profiles were analyzed with special software and cluster analysis.</p><p><b>RESULTS</b>A total of 3767 genes were identified to have significant differential expressions between these two cell lines (P<0.05), among which 281 genes showed twofold or higher differential expressions. Using MILANO software, we found 16 genes with probable close relation with liver metastasis of NPC.</p><p><b>CONCLUSION</b>The 16 genes differentially expressed between the two cell lines can be of importance in the investigation of the molecular mechanism of NPC liver metastasis and identification of molecular markers for prognostic evaluation.</p>

Expressions of human epidermal growth factor receptor 2 and vascular endothelial growth factor in primary or recurrent metastatic breast cancers / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expressions of human epidermal growth factor receptor 2 (Her-2) and vascular endothelial growth factor (VEGF) in primary and recurrent metastatic breast cancers and explore their relationship.</p><p><b>METHODS</b>The expressions of Her-2 and VEGF in 60 primary and recurrent metastatic breast cancers were detected using immunohistochemical methods. Their relationship was analyzed.</p><p><b>RESULTS</b>The positive rates of Her-2 and VEGF in the recurrent metastatic breast cancer were 40.00% and 53.33%, respectively, which were significantly higher than that in the primary breast cancer (18.33% and 31.67%) (P < 0.05). The total diversify rates of Her-2 and VEGF were 28.33% and 35.00%, respectively. Her-2 and VEGF expressions were significantly correlated between the primary and the recurrent metastatic breast cancers( P < 0.05).</p><p><b>CONCLUSIONS</b>Her-2 and VEGF may play synergic roles in the occurrence and development of breast cancer. Over-expressions of Her-2 and VEGF predict poor prognosis.</p>

Clinical research of 120 cases of primary small intestine malignant tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the clinical and pathological features, diagnosis, therapy and prognosis of primary small intestine malignant tumor.</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data from the 120 cases of primary small intestine malignant tumor.</p><p><b>RESULTS</b>Abdominal pain, gastrointestinal bleeding, anemia, abdominal mass and jaundice were the main clinical features. The pathology was confirmed by abdominal X-ray, gastrointestinal barium, CT, MRI, endoscopy and surgical exploration. Most tumors originated in the duodenum (54.1%), and adenocarcinoma (55.8%) was the main pathological type. The median survival time of the patients was 19.2 months and the 1-year survival rate was 55.4%. Chemotherapy did not seem to significantly improve the 1-year survival rate of the patients (P=0.842).</p><p><b>CONCLUSION</b>Primary small intestine malignant tumors lack specific clinical manifestations and surgical resection should be performed as early as possible.</p>

A randomized trial comparing oxaliplatin plus vinorelbine versus cisplatin plus vinorelbine for the treatment of patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the difference of efficacy, side-effects and quality of life in advanced non-small-cell lung cancer (NSCLC) patients treated with oxaliplatin plus vinorelbine or cisplatin plus vinorelbine.</p><p><b>METHODS</b>Eligible patients were randomly assigned to NL (oxaliplatin + vinorelbine) group and NP (cisplatin + vinorelbine) group in a 2:1 ratio. In the NL group, 70 evaluable cases were treated with oxaliplatin 130 mg/m(2) i.v. on day 2, and vinorelbine 25 mg/m(2) i.v. on days 1 and 8 in 21 days per cycle. In the NP group, 32 evaluable cases were treated with cisplatin 80 mg/m(2) i.v. divided to 2 - 3 days dosing, 21 days per cycle, and vinorelbine administered by the same way as in the NL group. The response rate, time to progression (TTP), one-year survival, side-effects and the quality of life were observed.</p><p><b>RESULTS</b>The response rate was 35.7% vs. 43.8% (P = 0.4), median TTP was 4.7 months vs. 5.5 months (P = 0.6), one-year survival rate was 38.5% vs. 58.6% (P = 0.07) in the NL and NP groups, respectively. Grade I-II neuro-sensory toxicity occurred significantly more frequent in NL group than in NP group (68.4% vs. 36.4%, P = 0.0017). However, Grade I-II granulocytopenia was significantly less occurred in NL group than in NP group (49.4% vs. 70.6%, P = 0.037). There was no statistically difference between the two groups regarding quality of life.</p><p><b>CONCLUSION</b>Due to good efficacy and tolerability, the NL regimen offered a new candidate for treating advanced NSCLC.</p>