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Miura D.,Nippon Medical School | Yoneyama K.,National Cancer Center East | Furuhata Y.,Red Cross | Shimizu K.,Nippon Medical School
Journal of Nippon Medical School

Materials and Methods: The subjects were 20 patients with HER2-positive breast cancer: 9 received the combination of trastuzumab (4 mg/kg as a loading dose and 2 mg/kg weekly) and paclitaxel (80 mg/m2 weekly) and 19 received monotherapy with trastuzumab. In blood samples (mononuclear cells) obtained before and 10 minutes after administration of chemotherapy, ADCC and the number of effector cells, including natural killer (NK) cells, monocytes, and CD64+ cells, were compared in each case. The ADCC was analyzed with a 51 Cr releasing assay using the SK-BR-3 cell line, and the fractions of NK cells (both CD16+ [FcγRIII] and CD56+) and CD64+ (FcγRI) cells were analyzed with flow cytometry.Introduction: An important mechanism by which trastuzumab inhibits the growth of human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is the activation of a host tumor response via antibody-dependent cell-mediated cytotoxicity (ADCC). Although paclitaxel has a synergistic effect in combination with trastuzumab, whether ADCC is enhanced by paclitaxel is not known. In the present study we examined whether adding paclitaxel to trastuzumab enhances ADCC and also investigated the kinetics of effector cells in ADCC.Results: The mean ADCC level increased 20% after trastuzumab monotherapy and 126% (p<0.05) after combination therapy with trastuzumab and paclitaxel. All 9 patients receiving combination therapy had increased ADCC levels. The number of NK cells increased 51% after trastuzumab monotherapy and 112% (p<0.05) after combination therapy. No significant changes were found in monocytes (39% increase) or CD64+ cells (53% increase) after trastuzumab monotherapy, but monocytes decreased 40% (p<0.05) and CD64+ cells decreased 24% after combination therapy.Conclusions: Adding paclitaxel to trastuzumab significantly enhances ADCC, with levels twice as great as with trastuzumab monotherapy, through a rapid recruitment of NK cells. This finding suggests that the combination of trastuzumab and paclitaxel has a stronger-thanexpected synergistic effect in HER2-positive breast cancer. © The Medical Association of Nippon Medical School. Source

Fujisawa D.,National Cancer Center East | Fujisawa D.,Keio University | Miyashita M.,Tohoku University | Nakajima S.,National Institute of Mental Health | And 4 more authors.
Journal of Affective Disorders

Background: Few epidemiological studies have examined complicated grief in the general population, especially in Asian countries. Therefore, this study aimed to explore the prevalence and predictors of complicated grief among community dwelling individuals in Japan. Methods: A questionnaire survey regarding grief and related issues was conducted on community dwelling individuals aged 40-79 who were randomly sampled from census tracts. Complicated grief was assessed using the Brief Grief Questionnaire. Stepwise logistic regression analysis was conducted in order to identify predictors of complicated grief. Results: Data from 969 responses (response rate, 39.9%) were subjected to analysis. The analysis revealed 22 (2.4%) respondents with complicated grief and 272 (22.7%) with subthreshold complicated grief. Respondents who were found to be at a higher risk for developing complicated grief had lost their spouse, lost a loved one unexpectedly, lost a loved one due to stroke or cardiac disease, lost a loved one at a hospice, care facility or at home, or spent time with the deceased everyday in the last week of life. Limitations: Limitations of this study include the small sample size, the use of self-administered questionnaire, and the fact that the diagnoses of complicated grief were not based on robust diagnostic criteria. Conclusions: The point prevalence of complicated grief within 10 years of bereavement was 2.4%. Complicated grief was maintained without significant decrease up to 10 years after bereavement. When subthreshold complicated grief is included, the prevalence of complicated grief boosts up to a quarter of the sample, therefore, routine screening for complicated grief among the bereaved is desired. Clinicians should pay particular attention to the bereaved families with abovementioned risk factors in order to identify people at risk for future development of complicated grief. © 2010 Elsevier B.V. All rights reserved. Source

Sugimoto M.,The Surgical Center | Sugimoto M.,Toho University | Gotohda N.,The Surgical Center | Gotohda N.,National Cancer Center East | And 7 more authors.
Journal of Hepato-Biliary-Pancreatic Sciences

Background: Postoperative pancreatic fistula (POPF) is a major, intractable complication after distal pancreatectomy (DP). Risk factor evaluation and prevention of this complication are important tasks for pancreatic surgeons. Methods: One hundred and six patients who underwent DP using a stapler for pancreatic division were retrospectively investigated. The relationship between clinicopathological factors and the incidence of POPF was statistically analyzed. Results: Clinically relevant, Grade B or C POPF by International Study Group of Pancreatic Fistula criteria occurred in 52 patients (49.1 %). Age, American Society of Anesthesiologists score, body mass index, and concomitant gastrointestinal tract resection did not influence the incidence of POPF. Use of a double-row stapler and a thick pancreatic stump were significant risk factors for POPF in multivariate analysis. Compression index was also shown to be an important factor in cases in which the pancreas was divided by a stapler. Conclusions: The most important risk factor for POPF after DP was suggested to be the thickness of the pancreatic stump, reflecting the volume of remnant pancreas. A triple-row stapler seemed to be superior to a double-row stapler in preventing POPF. However, triple-row stapler use in a thick pancreas is considered to be a future problem to be solved. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer Japan. Source

Yoshida T.,National Cancer Center Hospital East | Niho S.,National Cancer Center Hospital East | Toda M.,National Cancer Center East | Goto K.,National Cancer Center Hospital East | And 5 more authors.
Japanese Journal of Clinical Oncology

Objective: Magnesium supplementation has been reported to have a nephroprotective effect on cisplatin-induced renal dysfunction, but little evidence exists regarding the effect of magnesium preloading before cisplatin administration. We started to include magnesium preloading (8 mEq) in cisplatin-containing treatment regimens in January 2011. The aim of the present study was to evaluate whether magnesium preloading reduces cisplatin-induced nephrotoxicity. Methods: We retrospectively reviewed 496 thoracic malignancy patients treated with cisplatin (≥60 mg/m2)-containing regimens as a first-time chemotherapy between January 2009 and December 2011. We compared the incidence of Grade ≥2 serum creatinine elevation according to the Common Terminology Criteria for Adverse Events, version 4.0, between magnesium preloading group (n = 161 [32%]) and non-magnesium preloading group (n = 335 [68%]) during the first cycle and all cycles. Results: The median number of administered cycles was four in both groups. The incidence of Grade ≥2 serum creatinine elevation in magnesium preloading group was significantly lower during both the first cycle and all cycles than in the non-magnesium preloading group (4.9 versus 19.1% during the first cycle, and 14.2 versus 39.7% during all the cycles). A multivariate analysis indicated that magnesium preloading significantly reduced cisplatin-induced nephrotoxicity throughout the entire period from after the first administration (odds ratio: 0.262, 95% confidence interval: 0.106-0.596 during the first cycle, and odds ratio: 0.234, 95% confidence interval: 0.129-0.414 during all cycles). Conclusions: Magnesium preloading before cisplatin administration significantly reduced cisplatin-induced nephrotoxicity. © The Author 2014. Published by Oxford University Press. All rights reserved. Source

Suzuki C.,Karolinska University Hospital | Torkzad M.R.,Uppsala University Hospital | Jacobsson H.,Karolinska University Hospital | Astrom G.,Uppsala University Hospital | And 4 more authors.
Acta Oncologica

Background. Response Evaluation Criteria In Solid Tumors (RECIST) and WHO-criteria are used to evaluate treatment effects in clinical trials. The purpose of this study was to examine interobserver and intraobserver variations in radiological response assessment using these criteria. Material and methods. Thirty-nine patients were eligible. Each patient's series of CT images were reviewed. Each patient was classified into one of four categories according RECIST and WHO-criteria. To examine interobserver variation, response classifications were independently obtained by two radiologists. One radiologist repeated the procedure on two additional different occasions to examine intraobserver variation. Kappa statistics was applied to examine agreement. Results. Interobserver variation using RECIST and WHO-criteria were 0.53 (95% CI 0.33-0.72) and 0.60 (0.39-0.80), respectively. Response rates (RR) according to RECIST obtained by reader A and reader B were 33% and 21%, respectively. RR according to WHO-criteria obtained by reader A and reader B were 33% and 23% respectively. Intraobserver variation using RECIST and WHO-criteria ranged between 0.760.96 and 0.860.91, respectively. Conclusion. Radiological tumor response evaluation according to RECIST and WHO-criteria are subject to considerable inter- and intraobserver variability. Efforts are necessary to reduce inconsistencies from current response evaluation criteria. © 2010 Informa UK Ltd. Source

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