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Neri S.,National Cancer Center Hospital East | Yoshida J.,National Cancer Center Hospital East | Ishii G.,Research Center for Innovative Oncology | Matsumura Y.,National Cancer Center Hospital East | And 3 more authors.
Annals of Surgery | Year: 2014

Objective: We aimed to assess the prognostic significance of microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) in non-small cell lung cancer (NSCLC). Background: VPI is included in the current tumor-node- metastasis (TNM) classification in NSCLC; however, MVI is not incorporated in TNM classification. Methods: From August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection. In addition to conventional staging factors, we evaluated MVI histologically and analyzed its significance in NSCLC recurrence prognosis. The recurrence-free period in several NSCLC subgroups was analyzed using the Kaplan-Meier method and Cox regression analysis. Results: The proportion of patients with a 5-year recurrence-free period was 52.6% and 87.5%, respectively, in those with and without MVI (P < 0.001). Multivariate analysis showed that MVI, similarly to VPI, was found to be an independently significant predictor of recurrence [hazard ratio (HR): 2.78]. In particular, MVI and VPI were the 2 strongest significant independent predictors of recurrence in 1601 patients with pathological stage I disease treated without adjuvant chemotherapy (HR: 2.74 and 1.84, respectively). In each T subgroup analysis, evident and significant separation of the recurrence-free proportion curves were observed among the 3 groups (VPI and MVI absent, VPI or MVI present, and VPI and MVI present). Conclusions: This study demonstrated that MVI was a significant independent risk factor for recurrence in patients with a resected T1-4N0-2M0 NSCLC. Further data on MVI prognostic impact should be collected for the next revision of the TNM staging system. Copyright © 2014 Lippincott Williams & Wilkins.

Matsumura Y.,Research Center for Innovative Oncology
Japanese Journal of Clinical Oncology | Year: 2014

It is expected that the incidence of various adverse effects of anticancer agents maybe decreased owing to the reduced drug distribution in normal tissue. Anticancer agent incorporating nanoparticles including micelles and liposomes can evade non-specific capture by the reticuloendothelial system because the outer shell of the nanoparticles is covered with polyethylene glycol. Consequently, the micellar and liposomal carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Presently, several anticancer agent-incorporating nano-carrier systems are under preclinical and clinical evaluation. Several drug delivery system formulations have been approved worldwide. Regarding a pipeline of clinical development of anticancer agent incorporating micelle carrier system, several clinical trials are now underway not only in Japan but also in other countries. A Phase 3 trial of NK105, a paclitaxel incorporating micelle is now underway. In this paper, preclinical and clinical studies of NK105, NC-6004, cisplatin incorporating micelle, NC-6300, epirubicin incorporating micelle and the concept of cancer stromal targeting therapy using nanoparticles and monoclonal antibodies against cancer related stromal components are reviewed. © The Author 2014. Published by Oxford University Press. All rights reserved.

Nakanotani T.,Research Center for Innovative Oncology
Japanese journal of clinical oncology | Year: 2014

Cancer incidence and the number of cancer patients are increasing in today's aging society. The purpose of this study was to investigate the characteristics of elderly cancer patients' concerns and examine the association between their concerns and quality of life. This was a cross-sectional web-based survey completed by ambulatory cancer patients aged 20 years or older. The questionnaire on cancer patients' concerns, comprehensive concerns assessment tool and the European Organization for Research and Treatment of Cancer QLQ-C30 were distributed to the subjects. Multiple regression analysis was conducted to determine which patients' concerns significantly contributed to their quality of life. The final study population consisted of 807 cancer patients, among whom 243 (30%) were elderly (65 years or older). Elderly cancer patients had particular difficulty with self-management, psychological symptoms and medical information, and the prevalence of their concerns was generally lower than that of younger patients, with the exception of physical symptoms. Multiple types of elderly patients' concerns were independently associated with quality of life. We found that elderly cancer patients suffered from various concerns, thus multidisciplinary intervention is important for providing them with optimal care. The results of this study suggest that elderly cancer patients' quality of life will improve if their concerns are properly handled.

Al-Batran S.-E.,Krankenhaus Nordwest | Ducreux M.,Institute Gustave Roussy | Ohtsu A.,Research Center for Innovative Oncology
International Journal of Cancer | Year: 2012

The poor long-term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient-derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy-refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies. Copyright © 2011 UICC.

Yasunaga M.,Research Center for Innovative Oncology | Manabe S.,RIKEN | Matsumura Y.,Research Center for Innovative Oncology
Cancer Science | Year: 2011

Fibrin clots in non-malignant conditions form only at the onset or during the active stage of disease and disappear within a few weeks as a result of plasmin digestion or replacement with collagen. In contrast, fibrin clot formation and subsequent replacement with collagen in cancer persist for as long as the cancer cells survive in the body. We developed an anti-fibrin chimeric antibody that reacts with fibrin only, and not fibrinogen (the precursor of fibrin), and then attached an anticancer agent (ACA) to the antibody. Thus, the immunoconjugate did not create an immune complex in the blood stream and was selectively accumulated to fibrin clots in the tumor stroma to create a scaffold, from which effective sustained release of the ACA occurred. In a mouse model, the ACA diffused throughout the tumor tissue to damage both tumor cells and vessels, resulting in potent antitumor activity in stroma-rich spontaneous tumors. This new cancer stroma-targeting therapy may result in an increased duration of drug exposure and be a highly effective new therapy, particularly for refractory, stroma-rich cancers. © 2011 Japanese Cancer Association.

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