Gefitinib with or without Transarterial Infusion Chemotherapy (Cisplatin) for Large Nonsmall Cell Lung Cancer with Epidermal Growth Factor Receptor Mutations.

PURPOSE: To retrospectively investigate the safety and benefit of gefitinib plus transarterial infusion (TAI) therapy as a first-line treatment compared to gefitinib alone for patients with large (>7 cm) nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: Between January 2010 and December 2013, 92 consecutive treatment-naïve patients with large NSCLC with EGFR mutations, who were treated using gefitinib plus TAI (G+T, n = 42) or gefitinib alone (G, n = 50) were reviewed. The primary endpoints were the objective response rate (ORR) and tumor reduction rate. The secondary endpoints were progression-free survival (PFS) and overall survival (OS), and safety was also assessed. RESULTS: The baseline characteristics of the 2 groups were balanced, and no patients experienced treatment-related death. Toxicity outcomes did not differ between the G+T and G groups. The tumor reduction rate in the G+T group was significantly higher than that in the G group (42.9 vs 31.9%, P = .028). The ORR was 83% in the G+T group and 72% in the G group (P = .197). The median PFS was significantly longer in the G+T group than in the G group (14.0 vs 10.0 months, P = .023). The median OS was 30.0 months in the G+T group and 27.0 months in the G group (P = .235). CONCLUSIONS: This study suggests that compared with gefitinib alone, combination therapy with gefitinib plus TAI was well tolerated and potentially improved the tumor reduction rate and PFS in patients with large NSCLC with EGFR mutations.

Associations of nm23H1, VEGF-C, and VEGF-3 receptor in human prostate cancer.

We studied the expression of the non-metastatic clone 23 type 1 (nm23H1) gene, vascular endothelial growth factor (VEGF)-C, and its receptor VEGFR-3 using an in situ hybridization technique and immunohistochemical analyses with prostate cancer tissues and adjacent benign tissues of 52 human archival cases. The association between VEGF-C expression, microlymphatic count (MLC), and staining intensity for nm23H1 and VEGFR-3 was used to evaluate tumor metastasis and survival rate. MLC values were significantly higher in tumorous tissue than in non-cancerous tissue. VEGF-C mRNA, VEGFR-3, and nm23H1 were highly expressed in tumorous tissue. VEGFR-3 expression was greater in VEGF-C mRNA-positive tumors than in VEGF-C mRNA-negative tumors. The association of VEGFR-3 expression with VEGF-C mRNA and MLC suggested that the poor prognosis and tumor metastasis associated with VEGFR-3 expression may be due, in part, to its role in promoting angiogenesis. VEGF-C expression was significantly associated with tumor lymphangiogenesis, angiogenesis, and immune response as a potent multifunctional stimulating factor in prostate cancer. Expression of nm23H1 was significantly inversely correlated with lymph node metastasis. Furthermore, there was a strong negative correlation between the expression of nm23H1, VEGF-C mRNA, and MLC. These findings provide important information for prophylactic, diagnostic, and therapeutic strategies for prostate cancer.

Purification and characterisation of a novel antioxidant peptide derived from blue mussel (Mytilus edulis) protein hydrolysate.

Protein derived from blue mussel (Mytilus edulis) was hydrolysed using four kinds of proteases (pepsin, papain, neutrase and alcalase), and the neutrase hydrolysate (BNH) obtained by 3-h hydrolysis exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to other hydrolysates. By using ultrafiltration, gel filtration chromatography and reversed phase high performance liquid chromatography (RP-HPLC), a novel antioxidant peptide (BNH-P7) was isolated from BNH, and its amino acid sequence was identified as YPPAK (Tyr-Pro-Pro-Ala-Lys) with molecular weight of 574 Da. BNH-P7 exhibited good scavenging activity on DPPH radical, hydroxyl radical, and superoxide anion radical with EC(50) of 2.62, 0.228, and 0.072 mg/ml, respectively. BNH-P7 was also effectively against lipid peroxidation in a linoleic acid model system. The high activity of BNH-P7 was due to the small size and the presence of antioxidant and hydrophobic amino acid residues (Tyr and Pro) within its sequence.

Coexpression of the mutated BRCA1 mRNA and p53 mRNA and its association in Chinese prostate cancer.

The mutations of BRCA1 and p53 genes have been simultaneously characterized in many tumors. However, their coexpression and associations have not been investigated quantitatively in prostate cancer. In the present study, the expressions of the mutated BRCA1 mRNA and p53 mRNA were examined in 48 Chinese prostate cancer cases and 10 corresponding adjacent benign tissues with in situ hybridization. The 5-year survival rates of the corresponding patients after operation were investigated. The results showed that the positive expressions of the mutated BCRA1 mRNA and p53 mRNA are involved in prostate cancer (P < 0.05). Moreover, there is a closed negative association between the expressions of the mutated BRCA1 gene and p53 gene in the mRNA level with the progression, angiogenesis, metastasis, and survival rate of prostate cancer. Their coexpression and negative association suggest that the two altered tumor suppressor genes might interact functionally in prostate cancer to provide a potential signal determining a prognosis of the tumor metastasis and survival rate. Further work will be done to elucidate the interaction mechanisms in prostate cancer.

[Determination of 27 inorganic elements in Limonium bicolor by ICP-MS using microwave digestion for sample preparation].

An inductively coupled plasma mass spectrometry (ICP-MS) for determination of the contents of 27 inorganic elements in Limonium bicolor after microwave digestion of the sample was developed. The accuracy of the method was evaluated by the analysis of corresponding inorganic elements in standard reference materials (GBW 07605), and matrix effect and signal drift were compensated by using the internal standard elements (Ge, In and Bi). By applying the proposed method, the contents of 27 inorganic elements in Limonium bicolor collected from Dongying (Shandong Province of China) were determined. The precision of measurement ranges from 1.5% to 9.7% in terms of relative standard deviation. The recoveries and the limits of detection are in the range of 92.4%-107.2% and 0.002-0.081 microg x L(-1), respectively. It is indicated that the proposed method has the advantages of simplicity, speediness and sensitivity. The results showed that the Limonium bicolor are rich in major elements Na, K, Ca and Mg and trace elements Fe, Mn, Zn, Cr and Cu. This paper provides scientific basis for deeply studying the relation between the inorganic elements and the drug effects of Limonium bicolor.

[Study on the correlation between the expressions of nm23H1 mRNA, VEGF-C mRNA and lymphatic metastases, survival rate with gastric cancer].

The correlations between the expression of nm23H1 mRNA,VEGF-C mRNA, VEGFR-3 and neoangiogenesis, hyperplasia of micro-lymphatic, tumor metastases in gastric cancer were studied, the results supplied an experimental foundation for clinical treatment and prognosis. All the specimens were marked by VEGFR-3 antibody, the expressions of nm23H1 mRNA, VEGF-C mRNA were detected in 78 cases of gastric cancer in situ hybridization with EnVision and Leica-Qwin computer image analysis system. The Weidner's highest vessel density counting method was used to analyse micro-lymphatics count (MLC) of the specimens, and the patients' viability after operation was investigated. The positive expression of nm23H1 mRNA in gastric cancer was 69.23% (54 cases). There was negative correlation between the positive expression of nm23H1 mRNA and lymph node metastasizing, TNM staging, MLC (P < 0.01 or P < 0.05). The expression of VEGF-C mRNA was 46.15% (36 cases). It was positive related to the lymph node metastasis, TNM stages, MLC in gastric cancer (P < 0.01 or P < 0.05), and was significantly different compared with adjacent nontumorous tissue (P < 0.01 or 0.05). The expression of nm23H1 in stage I and II gastric cancer was high, while in stage III and IV the expression was lower or even none. The MLC (8.37 +/- 2.29/mm2) in gastric cancer was higher than that in adjacent nontumorous tissue (4.82 +/- 3.48/mm2), which has statistical significance (P < 0.05). There was negative correlation between the expression of nm23H1 mRNA and VEGFR-3 (p < 0.05, r = 0.8479), but positive correlation between VEGF-C mRNA and VEGFR-3 (P < 0.05, r = 0.8362). The MLC (10.82 +/- 2.51/mm2) in those who died in five years (48 cases) was higher than that (6.53 +/- 2.09/mm2) in those who were still alive, the difference has statistical significance (P < 0.05). In different tumor pathology grading, different differentiation, the nm23H1 positive expression is significantly different (P < 0.05). Higher the nm23H1 expressed, lower the tumor lymph metastasized, but the viability rate was higher, so the nm23H1 gene was thought to have the effect of suppressing gastric cancer occurring and lymph metastasizing. Higher the VEGF-C mRNA expressed, higher the tumor lymph metastasized, but the viability rate was lower. There is close correlation between the VEGFR-3 expression and gastric cancer lymph metastasizing. The higher MLC level indicated neoangiogenesis in gastric cancer. VEGF-C promote neoangiogenesis induced by tumor and play an important role in lymph metastasizing.

[Study on the correlationship between the expression of nm23H1mRNA, TGF-beta1mRNA and tumor metastases, survival rate with prostate cancer].

All the specimens were marked by CD31 antibody, the expression of nm23HlmRNA, TGF-beta1mRNA was detected in 42 cases of prostate cancer in situ hybridization with EnVision and Leica-Qwin computer image analysis system. The Weidner's highest vessel density counting method was used to analysis the microvessel density(MVD) of the specimens,and the patients' viability rate after operation was investigated. The correlation between the expression of nm23H1mRNA, TGF-betamRNA,CD31 and neoangiogenesis, hyperplasia of microvessel, tumor metastases in prostate cancer was studied. The positive expression of nm23H1mRNA in prostate cancer was 66.67% (28 cases). There was negative correlation between the positive expression of nm23H1mRNA and bone metastasizing, TNM staging,MVD in prostate cancer (P < 0.05). The positive expression of TGF-beta1mRNA was 78.75% (33 cases), and was positive correlative to the bone metastasis, TNM stages, MVD in prostate cancer (P < 0.05). It is significantly different (P < 0.01 or P < 0.05) with that in adjacent nontumorous tissue. The MVD (78.51 +/- 10.29/mm2) in prostate cancer was significantly (P < 0.05) higher than that in adjacent nontumorous tissue (34.19 +/- 9.27/mm2). The MVD (92.41 +/- 15.42/mm2) in those who died in five years (18 cases) was significantly higher (P < 0.05) than that (62.79 +/- 13.58/mm2) in those who were still alive. In tumor pathology grading,different differentiation, the difference of nm23H1mRNA positive expression was statistically significant (P < 0.05). Higher the nm23H1mRNA expressed,lower the bone metastasized,and higher the viability rate was. Therefore, the nm23H1 gene was thought to have the effect of suppressing prostate cancer occurring and bone metastasizing. Higher the TGF-beta1mRNA expressed, higher the tumor bone metastasized, and lower the viability rate was. Therefore, the TGF-beta1 gene was thought to have the promote genesis and metastasize of prostate cancer. There is close correlation between the CD31 expression, MVD and prostate cancer bone metastasizing. The higher MVD level indicated neoangiogenesis in prostate cancer. TGF-beta1mRNA promote neoangiogenesis induced by tumor and play an important role in bone metastasizing.

[Correlation between the expression of VEGF-C mRNA, VEGFR-3, CD31 and tumor metastases in Chinese with prostate cancer].

The expressions of VEGF-C mRNA, VEGFR-3 and CD31 were studied in order to investigate the correlation between them and neoangiogenesis, hyperplasia of micro-lymphatics and tumor metastases. 34 cases of prostate cancer tissue and 12 cases of adjacent nontumorous tissue specimens were tested. They were marked by VEGFR-3 and CD31 with immunohistochemistic staining and analyzed with image, the micro-lymphatics count (MLC) and microvessel density (MVD) were counted using Weidner's highest vessel density count method; the expression of VEGF-C mRNA was inspected in situ hybridization. The expression of VEGF-C mRNA was 44.12% positive in 34 cases of prostate cancer, the MLC (8.26 +/- 2.73)mm2 and MVD (74.82 +/- 11.76)mm2 in prostate cancer were significantly higher than those in adjacent nontumorous tissue (MLC, 4.82 +/- 3.48/mm2; MVD, 32.86 +/- 5.41/mm2). In addition, there was a correlation between the expression of VEGF-C mRNA and micro-lymphatics metastases and there was a positive correlation between the expression of VEGFR-3 and CD31. The expressions of VEGF-C mRNA , MLC, MVD in stage III and IV and those who have lymph metastasis were higher than those in stage I and II and those who have no lymph metastasis; the expressions of VEGFR-3 and CD31 in VEGF-C mRNA positive groups were significantly higher than those in negative groups. The difference of histopathologic grading in prostate cancer had no statistical significance. VEGF-C could accelerate the hyperplasia of micro-lymphatics and neoangiogenesis induced by tumor and play an important role in tumor lymph metastases. There was a close correlation between the expressions of VEGFR-3, CD31 and tumor metastases. The increase of MLC and MVD on prostate cancer indicated the hyperplasia of new micro-lymphatics and neoangiogenesis in the tumor tissue, which could also be a signal to determine the tumor metastases in clinic.