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We attempted to investigate immunohistochemical expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PD-ECGF), c-erbB-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 using surgical specimens of 119 non-small-cell lung carcinoma (NSCLC) cases and to evaluate the relationship between the expression levels of each molecule and clinicopathological factors or prognosis. VEGF expression levels were significantly associated with the local invasion (P = 0.0001), lymph node involvement (pN-factor) (P = 0.0019), pathological stage (p-stage) (P = 0.0027) and lymphatic permeation (P = 0.0389). PD-ECGF expression levels were associated with pN-factor (P = 0.0347). MMP-2 expression levels were associated with pN-factor (P = 0.004) and lymphatic permeation (P = 0.0056). Also, MMP-9 expression levels showed a significant correlation to local invasion (P = 0.0012), pN-factor (P = 0.0093) and p-stage (P = 0.0142). Multivariate analysis showed VEGF to be the most related to local invasion (P = 0.0084), and MMP-2 was the only factor with significant independent impact on lymphatic permeation (P = 0.0228). Furthermore, log-rank analysis showed significant association with poor survival by VEGF, bFGF, MMP-2 and MMP-9. Especially, combined overexpression of VEGF and MMP-2 revealed poor prognosis, our study might provide a basis for the better evaluation of biological characteristics and a new therapeutic strategy based on chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

Cisplatin-based (CDDP-based) adjuvant chemotherapy of nonsmall cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (H69 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-Stransferase-p (GST-p). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-p with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDPresistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p 5 0.007). In addition, cases that were both RCN-positive and GST-p-negative showed a statistically significantly better outcome (p 5 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-p might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy. ' 2005 Wiley-Liss, Inc.Key words: reticulocalbin; glutathione-S-transferase-p; cisplatin; individual therapy; non-small cell lung cancer Death due to lung cancer is still increasing in Japan and most Western countries, despite intensive application of various therapeutic strategies, and it is still the leading cause of cancer death in Japan. Though the opportunities of relatively early detection and treatment increase, still more than half of cases of primary lung cancer show advanced stage at the initial definitive diagnoses. Several years ago, we routinely carried out postoperative adjuvant chemotherapy using platinum (cisplatin [CDDP] or carboplatin) for patients with advanced stage non-small cell lung carcinoma (NSCLC) because distant metastasis occurred frequently after surgical treatment only. Clinically favorable outcome was not obtained, however, and the 5-year survival of Stage IIIA was approximately 25%, despite postoperative adjuvant chemotherapy. It had been believed that the efficacy of adjuvant chemotherapy in surgically resected lung cancer was controvers...

Although postoperative adjuvant chemotherapy (PAC) with uracil -tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil -tegafur. However, we were unable to select responders to uracil -tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.

Background: Side effects of chemotherapy are major issues for cancer patients and there are few methods to release these. However, traditional Chinese medicine is one of the options for these patients. This study is to evaluate one traditional Chinese empirical formula -the Ciji Hua'ai Baosheng Formula (CHBF) on apoptosis related factors in a transplanted tumor chemotherapy model. Materials and Methods: H 22 hepatoma cells were injected into peritoneal cavity and Cytoxan (CTX) (200mg/kg) was used to treat these carcinoma cells. Mice were divided into control, CTX control, and CTX plus three different concentrations of CHBF groups. H 22 hepatoma cells proliferation, serum levels of apoptosis related factors, and bone marrow cyclin D1 expression was evaluated. Results: After treatment of CHBF, H 22 hepatoma cell proliferation was lower than that in CTX group. The pro-apoptosis related proteins Bax and Caspase-3 were elevated while anti-apoptosis related protein Bcl-2 was reduced. Moreover, serum epidermal growth factor receptor level and bone marrow cyclin D1 expression were significantly reduced in CHBF treated groups. Conclusion: The Ciji Hua'ai Baosheng Formulae could modulate apoptotic and proliferative factors in a model of tumor with chemotherapy, which may be the mechanisms why it can release chemotherapy related side effect in patients with cancer.

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