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Sample records for platinum based chemotherapy

  1. [Comparison of the effectiveness of platinum-based chemotherapy versus non-platinum-based chemotherapy for triple-negative breast cancer with metastases confined to the lungs].

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    Hong, Ruoxi; Ma, Fei; Shi, Xiuqing; Li, Qing; Zhang, Pin; Yuan, Peng; Wang, Jiayu; Fan, Ying; Cai, Ruigang; Li, Qiao; Xu, Binghe

    2014-10-01

    To compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC). Sixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR). In the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases. Compared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.

  2. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antag

  3. Pharmacogenomics of platinum-based chemotherapy sensitivity in NSCLC: toward precision medicine.

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    Yin, Ji-Ye; Li, Xi; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-08-01

    Lung cancer is one of the leading causes of cancer-related death in the world. Platinum-based chemotherapy is the first-line treatment for non-small-cell lung cancer (NSCLC), however, the therapeutic efficiency varies remarkably among individuals. A large number of pharmacogenomics studies aimed to identify genetic variations which can be used to predict platinum response. Those studies are leading NSCLC treatment to the new era of precision medicine. In the current review, we provided a comprehensive update on the main recent findings of genetic variations which can be used to predict platinum sensitivity in the NSCLC patients.

  4. Overexpression of MAC30 is Resistant to Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer.

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    Chen, Ruhua; Fen, Yan; Lin, Xubo; Ma, Tieliang; Cai, Hourong; Ding, Hui

    2016-12-01

    Adjuvant platinum-based chemotherapy has developed its stability as the first-line treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the prognostic value of meningioma-associated protein (MAC30) on adjuvant platinum-based chemotherapeutic response and survival in patients with NSCLC. A total of 174 retrospective stage III B to IV Chinese patients with NSCLC were enrolled in the study. Among all cases, 85 patients were given platinum-based chemotherapy and another 89 patients received molecularly targeted therapy. The expression of MAC30 in tumor samples was confirmed via immunohistochemical staining to correlate with the therapeutic response and survival of patients. Patients having NSCLC with MAC30 overexpression showed a poorer response to platinum-based chemotherapy, while there was no prognostic value of MAC30 expression on molecularly targeted therapy. Further, patients receiving platinum-based chemotherapy with enhanced MAC30 expression exhibited shorter survival. A multivariate analysis exhibited that increased MAC30 expression was an independent prognostic factor for overall survival in patients having NSCLC with platinum-based chemotherapy. In conclusion, patients having NSCLC with higher MAC30 expression resisted to platinum-based chemotherapy and exhibited worse survival. © The Author(s) 2015.

  5. ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy

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    EL Baiomy, Mohamed Ali; El Kashef, Wagdi F

    2017-02-01

    Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression would improve response and survival. This study was conducted to assess the impact of ERCC1 expression on PFS, OS and response rates in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. Methods: From June 2012 to November 2013, 52 metastatic triple negative breast cancer patients were enrolled. ERCC1 protein expression was detected from pretreatment biopsies by Immunohistochemistry. All patients received cisplatin plus paclitaxel. The primary end point was the impact of ERCC1 expression on PFS and OS. Results: 34 patients (65.4%) showed positive ERCC1 expression while 18 (34.6%) proved negative. Positive ERCC1 expression was associated with short PFS (median, 5 months vs. 7 months; P = 0.043), short OS (median, 9 months vs. 11 months; P = 0.033) and poor response to cisplatin based chemotherapy (P = 0.046). Conclusions: This prospective study further validated ERCC1 as a reliable biomarker for customized chemotherapy in metastatic triple negative breast cancer patients. High expression of ERCC1 was thereby fond to be significantly associated with poor outcome in patients treated with platinum based chemotherapy.

  6. Relationship between BRCA1 Expression and Efifcacy of Platinum-based Chemotherapy in Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Guanghui; Li Yu; Liu Yi

    2014-01-01

    Objective:To explore the expression of breast cancer susceptibility gene 1 (BRCA1) in human colorectal cancer and its correlation with efifcacy of platinum-based chemotherapy. Methods:A total of 78 samples from patients with colorectal cancer and receiving platinum-based chemotherapy were selected, and meanwhile 14 cases of normal colonic mucosa samples were selected as a normal control, 12 cases of non-cancerous tissue in colorectal cancer samples were selected as a pericarcinorma control. The expression of BRCA1 in these tissues was detected using immunohistochemical S-P method, and all patients treated with drugs were followed-up for survival time. Results: The positive rate of BRCA1 expression in colorectal cancer tissue was 52.6%, signiifcantly lower than that in the control groups. BRCA1 expression was closely associated with histological differentiation degrees (χ2=14.16,P=0.001), but not with the age, gender, local inifltration, lymph node metastasis and TNM staging. Comparing with those with positive BRCA1 expression, the patients with negative BRCA1 expression after oxaliplatin-based chemotherapy had signiifcantly longer disease-free survival (DFS) (P=0.032). Conclusion:Application of oxaliplatin-based chemotherapy in the patients with negative BRCA1 expression can obtain the survival beneift, and the level of BRCA1 expression can be useful in the selection of chemotherapy regimens and evaluation of prognosis for patients with colorectal cancer after surgery.

  7. Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer

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    Storr, Sarah J; Safuan, Sabreena; Woolston, Caroline M; Abdel-Fatah, Tarek; Deen, Suha; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Ovarian cancer is routinely treated with surgery and platinum-based chemotherapy. Resistance is a major obstacle in the efficacy of this chemotherapy regimen and the ability to identify those patients at risk of developing resistance is of considerable clinical importance. The expression of calpain-1, calpain-2 and calpastatin were determined using standard immunohistochemistry on a tissue microarray of 154 primary ovarian carcinomas from patients subsequently treated with platinum-based adjuvant chemotherapy. High levels of calpain-2 expression was significantly associated with platinum resistant tumours (P = 0.031). Furthermore, high expression of calpain-2 was significantly associated with progression-free (P = 0.049) and overall survival (P = 0.006) in this cohort. The association between calpain-2 expression and overall survival remained significant in multivariate analysis accounting for tumour grade, stage, optimal debulking and platinum sensitivity (hazard ratio = 2.174; 95% confidence interval = 1.144–4.130; P = 0.018). The results suggest that determining calpain-2 expression in ovarian carcinomas may allow prognostic stratification of patients treated with surgery and platinum-based chemotherapy. The findings of this study warrant validation in a larger clinical cohort. PMID:22435971

  8. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu;

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  9. Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer

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    Aparicio, Ana M.; Harzstark, Andrea L.; Corn, Paul G.; Wen, Sijin; Araujo, John C.; Tu, Shi-Ming; Pagliaro, Lance C.; Kim, Jeri; Millikan, Randall E.; Ryan, Charles J.; Tannir, Nizar M.; Zurita, Amado J.; Mathew, Paul; Arap, Wadih; Troncoso, Patricia; Thall, Peter F.; Logothetis, Christopher J.

    2013-01-01

    Purpose Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. Experimental Design A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population. PMID:23649003

  10. Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy.

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    Belen Sadaba

    Full Text Available BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV or oral routes, but subcutaneous (SC administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA. RESULTS: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p=0.160. Bioavalability of SC palonosetron was 118% (95% IC: 69-168. Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. CONCLUSIONS: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01046240.

  11. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

    OpenAIRE

    2008-01-01

    Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultraso...

  12. Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity.

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    Stojanovska, Vanesa; Sakkal, Samy; Nurgali, Kulmira

    2015-02-15

    The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

  13. Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

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    Lu, Jun; Zhao, Haitao; Li, Sha; Tian, Zhongze; Zhu, Xianghui; Wang, Hongyi; Fu, Hua

    2015-01-01

    Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair. The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer. In total, 60 triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed. All of the patients received a platinum-based chemotherapy for 4 cycles in median and achieved an overall response rate of 66.7%, showing a comparative good response towards platinum-based chemotherapy among triple negative breast cancer. Fifty-three of the 60 patients had got the results of ERCC2 rs1799793 polymorphisms after MassARRAY detection. The proportion of GG genotype and GA genotype was 81.1% and 18.9% respectively. The response rate of the rs1799793 GG genotype group was 69.8%, while the GA genotype group only had a response rate of 30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030). ERCC2 rs1799793 polymorphism may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for triple negative breast cancer patients treated with platinum compounds.

  14. Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Chi Pan; Suzhan Zhang; Jianjin Huang

    2013-01-01

    In the past decade, the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically influenced the therapeutic strategies for treating lung cancer, but with tumor progression and drug resistance, patients will ultimately develop reduced sensitivity to EGFR-TKIs. How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research. Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs. However, results of pre-clinical and clinical studies have been inconsistent. The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research. Therefore, systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.

  15. EMT-like circulating tumor cells in ovarian cancer patients are enriched by platinum-based chemotherapy.

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    Chebouti, Issam; Kasimir-Bauer, Sabine; Buderath, Paul; Wimberger, Pauline; Hauch, Siegfried; Kimmig, Rainer; Kuhlmann, Jan Dominik

    2017-07-25

    Assuming that tumor cell dissemination requires a shift to a mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal-transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients and inquired, how their molecular phenotypes respond to platinum-based chemotherapy and influence outcome. Before surgery, overall detection rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed (30%) and were mutually exclusive to epithelial CTCs in the majority of patients (82%). After chemotherapy, EMT-like CTCs increased up to 52%, accompanied by the "de novo" emergence of PI3Kα+/Twist+ EMT-like CTCs. Before surgery, PI3K+ EMT-like CTCs in combination with epithelial CTCs indicated decreased OS (p = 0.02) and FIGO I-III patients with residual tumor burden after surgery were more likely to be positive for EMT-like CTCs after chemotherapy (p = 0.02). In the latter group, epithelial CTCs alone significantly correlated with decreased PFS and OS (p = 0.02, p = 0.002), supported by an additional inclusion of PI3K+ CTCs (OS, p = 0.001). Blood samples of 91 ovarian cancer patients before surgery and 31 matched samples after adjuvant chemotherapy were evaluated for CTCs with the AdnaTest ovarian cancer and EMT-1, analyzing the epithelial-associated transcripts EpCAM, Muc-1 and CA125 and the EMT-associated transcripts PI3Kα, Akt-2 and Twist. Platinum-based chemotherapy seems to select for EMT-like CTCs in ovarian cancer patients and provokes a shift towards PI3Kα and Twist expressing CTCs, which may reflect clonal tumor evolution towards therapy resistance. It has to be determined, whether this CTC subgroup may serve as a biomarker to identify patients at high risk.

  16. Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review

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    Wang Min-Yan

    2010-10-01

    Full Text Available Abstract Background Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC, but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi Fuzheng Injection(SFI combined with platinum-based chemotherapy for advanced NSCLC. Methods Pubmed, Cochrane Library, EMBASE, CNKI, and CBM search were organized for all documents published, in English and Chinese, until April 2010. The randomized controlled clinical trials were selected based on specific criteria, in which a SFI plus platinum-based chemotherapy treatment group was compared with a platinum-based chemotherapy control group for patients with advanced NSCLC. The quality of studies was assessed by modified Jadad's scale, and Revman 4.2 software was used for data syntheses and analyses. Results Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response (RR, 1.19; 95% CI, 1.07 to 1.32; P = 0.001 and performance status ((RR, 1.57; 95% CI, 1.45 to 1.70; P P = 0.016. Conclusions SFI intervention appears to be useful to increase efficacy and reduce toxicity when combined with platinum-based chemotherapy for advanced NSCLC, although this result needs to be further verified by more high-quality trials.

  17. Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy

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    Helbekkmo, Nina; Aasebø, Ulf; Sundstrøm, Stein H

    2008-01-01

    BACKGROUND: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients...

  18. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy.

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    Miao, Yi; Yan, Qin; Li, Shuangdi; Li, Bilan; Feng, Youji

    2016-06-07

    The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR platinum resistance in patients with EOC.

  19. Heat shock protein 70 as a predictive marker for platinum-based adjuvant chemotherapy in patients with resected non-small cell lung cancer.

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    Park, Tai Sun; Kim, Hye-Ryoun; Koh, Jae Soo; Jang, Seung Hun; Hwang, Yong Il; Yoon, Ho Il; Chung, Jin-Haeng; Kim, Cheol Hyeon; Kim, Sung-Soo; Kim, Woo Sung; Jo, Jungmin; Lee, Jae Cheol; Choi, Chang-Min

    2014-11-01

    Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy. Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy. Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P=0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P=0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362-0.796; P=0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419-1.051; P=0.080). Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractor. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10. 0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy.There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8 % of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia,and 8 (36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death.Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

  1. Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

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    Malek B Hannouf

    Full Text Available PURPOSE: To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system. METHODS: We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%. RESULTS: In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab. CONCLUSION: The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

  2. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

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    Zang JL

    2017-01-01

    Full Text Available Jialan Zang,1–3,* Yong Hu,1,2,* Xiaoyue Xu,1,2 Jie Ni,1,2 Dali Yan,1,2 Siwen Liu,4 Jieyu He,5 Jing Xue,4 Jianzhong Wu,4 Jifeng Feng2 1The Fourth Clinical School of Nanjing Medical University, 2Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 3Department of Oncology, The First Hospital of Harbin City, Harbin, 4Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, 5Department of Public Health, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Aim: This study was designed to investigate the predictive and prognostic values of serum vascular endothelial growth factor (VEGF level in non-small cell lung cancer (NSCLC patients treated with platinum-based chemotherapy. Methods: Patients’ peripheral blood samples were collected prior to chemotherapy and after 1 week of the third cycle of combination chemotherapy. Serum VEGF levels were evaluated through Luminex multiplex technique. Between September 2011 and August 2015, a total of 135 consecutive advanced or recurrent histologically verified NSCLC patients were enrolled in the study. Moreover, all the patients received platinum-based combination chemotherapy as a first-line treatment. Results: No significant associations were found between pretreatment serum VEGF levels and clinical characteristics, such as sex (P=0.0975, age (P=0.2522, stage (P=0.1407, lymph node metastasis (P=0.6409, tumor location (P=0.3520, differentiated degree (P=0.5608, pathological (histological type (P=0.4885, and response to treatment (P=0.9859. The VEGF load per platelet (VEGFPLT levels were not correlated with sex, age, primary tumor site, and pathological type in NSCLC patients (all P>0.05. The median survival time of progression-free survival (PFS was 6.407 and 5.29 months in the low and high groups, respectively, when using 280 pg/mL VEGF level as the cutoff point (P=0.024. Conclusion

  3. XRCC3 Thr241Met polymorphism and clinical outcomes of NSCLC patients receiving platinum-based chemotherapy: a systematic review and meta-analysis.

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    Xiao-yong Shen

    Full Text Available INTRODUCTION: X-ray repair cross-complementing protein 3 (XRCC3 is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC patients receiving platinum-based chemotherapy. METHODS: A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS and progression-free survival (PFS were analyzed. RESULTS: A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099-2.072, Pheterogeneity  = 0.618. The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651-1.356, Pheterogeneity  = 0.112 or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539-1.710, Pheterogeneity  = 0.198. Additionally, no evidence of publication bias was observed. CONCLUSIONS: This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.

  4. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

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    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  5. Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

    Science.gov (United States)

    Williams, J I; Weitman, S; Gonzalez, C M; Jundt, C H; Marty, J; Stringer, S D; Holroyd, K J; Mclane, M P; Chen, Q; Zasloff, M; Von Hoff, D D

    2001-03-01

    Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.

  6. Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

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    Chong’an XU

    2011-12-01

    Full Text Available Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung cancer (NSCLC. The aim of this study is to investigate the relationship between X-ray repair cross complementing protein 1 (XRCC1 and X-ray repair cross complementing protein 3 (XRCC3 gene polymorphisms and the chemosensitivity of platinum-based chemotherapy in patients with advanced NSCLC. Methods Genomic DNA were extracted from the sera of a total of 130 patients with advanced NSCLC who received platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms and chemotherapy sensitivity was analyzed. Results A total of 130 patients with advanced NSCLC received platinum-based chemotherapy, with an overall response rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic polymorphisms, but not XRCC3 241, were found to be related to the chemosensitivity. The objective response rate of the patients with at least one XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020. The objective response rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336, 95%CI: 0.156-0.722, P=0.005. Combined effects between XRCC1 194 and XRCC1 399 were observed. The objective response rate of the patients with at least one XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%, OR=3.467, 95%CI: 1.223-9.782, P=0.019. Moreover, XRCC1 and XRCC3 have a combined effect in predicting chemosensitivity

  7. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy

    DEFF Research Database (Denmark)

    Bellmunt, J; Fougeray, R; Rosenberg, J E

    2013-01-01

    To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy....

  8. Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

    Science.gov (United States)

    Lee, Seung Hyeun; Choi, Sue In; Lee, Ji Sung; Kim, Chul Hwan; Jung, Won Jai; Lee, Eun Joo; Min, Kyung Hoon; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Kim, Je Hyeong; Lee, Sang Yeub; Shin, Chol; Shim, Jae Jeong; Kang, Kyung Ho; In, Kwang Ho

    2017-01-01

    Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

  9. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

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    Citro Gennaro

    2008-05-01

    Full Text Available Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations.

  10. Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study

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    Dattatreyo Chatterjee

    2014-01-01

    Full Text Available Objectives: Toxicity of cancer chemotherapy may be affected by nutritional status of patients which is reflected in the body mass index (BMI. We sought to assess whether the adverse drug reaction (ADR profile of platinum-based chemotherapy varies with BMI status. Materials and Methods: Adult patients of either sex, suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach, colon and started on platinum-based chemotherapy as initial treatment were included. BMI at chemotherapy commencement was obtained from medical records. Events were recorded and graded as per Eastern Co-operative Oncology Group Common Toxicity Criteria-patients′ complaints; clinically evident signs and laboratory reports were considered. Frequencies of individual adverse events were compared between low BMI (<18.5 kg/m 2 and satisfactory BMI groups. Similar comparisons were done for events with grades 2 or 3 severities. Results: A total of 50 patients were observed over a 3-month period of whom 17 (34% belonged to the low BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and paresthesia were the commonly observed ADRs. The frequencies of anemia (P = 0.152 and vomiting (P = 0.140 and severity of grades of nausea (P = 0.066, anemia (P = 0.120 and paresthesia (P = 0.128 showed a higher trend in the low BMI group though differences were not statistically significant. The frequencies of tinnitus (P = 0.021 and paresthesia overall (P = 0.036 were significantly higher in the low BMI group. Conclusion: ADR profile of primary platinum-based chemotherapy appears to be partly influenced by BMI. This suggests the importance of maintaining adequate nutrition in patients and the need for greater vigilance in those with low BMI.

  11. Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy

    Science.gov (United States)

    Omersa, Daniel; Cufer, Tanja; Marcun, Robert

    2017-01-01

    Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. Methods This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). Results Overall, 41 patients (mean age 61 ± 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). Conclusions In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.

  12. Association of POLK polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients.

    Science.gov (United States)

    Shao, Minhua; Jin, Bo; Niu, Yanjie; Ye, Junyi; Lu, Daru; Han, Baohui

    2014-11-01

    Lung cancer is the leading cause of tumor-derived death. Although target therapy is proven very efficient, traditionally platinum-based chemotherapies are still primary treatment for most patients. Platinum can suppress the tumor growth and impair normal cells together. The primary aim of the present study was to study the potential role of translesion synthesis (TLS) that might play in platinum-chemotherapy tolerance and side-effect. In present study, a total of 663 patients who were newly histologically diagnosed with advanced NSCLC (aNSCLC) were enrolled. Treatment response was classified into four categories: complete response, partial response, stable disease, and progressive disease. Incidence of gastrointestinal and hematological toxicities was assessed twice a week during the whole first-line treatment. Eleven SNPs of POLK were genotyped. The associations between SNPs and treatment response or toxicity were analyzed with logistic regression model. Cox regression was used for survival analysis between SNPs and progression-free survival or overall survival. We identified that rs3213801 and rs5744533 showed complete linkage in the present study, and they were significantly associated with treatment response (adjusted P = 0.044), together with rs5744655 (adjusted P = 0.039). rs1018119 was correlated with gastrointestinal toxicity in smokers specially (adjusted P = 0.041). Besides, rs3756558 was associated with hematological toxicity and overall toxicity in smokers and combined cohort with additive model. We also identified the significant association between two SNPs, rs10077427 and rs5744545, and PFS. The polymorphism of POLK, an important gene in TLS, participates in platinum-chemotherapy tolerance and side-effect.

  13. Prognostic impact of 18F-FDG uptake on PET in non-small cell lung cancer patients with postoperative recurrence following platinum-based chemotherapy.

    Science.gov (United States)

    Kaira, Kyoichi; Yamamoto, Nobuyuki; Kenmotsu, Hirotsugu; Murakami, Haruyasu; Ono, Akira; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2014-03-01

    Whether fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake within tumor cells differs between primary and recurrent lung cancers is unknown. The aim of this study was to investigate the prognostic significance of (18)F-FDG uptake by comparing that measured preoperatively at the primary site to that measured postoperatively at sites of non-small cell lung cancer (NSCLC) recurrence. Only patients with postoperative recurrences who received platinum-based chemotherapy as the initial treatment after recurrence were included in the study. Fifty-two patients underwent (18)F-FDG positron emission tomography (PET) examinations before thoracotomy and at the time of recurrence after curative surgery. All recurrences were treated with platinum-based chemotherapy. (18)F-FDG uptake in the preoperative primary tumors was significantly higher than that in the recurrent tumors (p=0.028), demonstrating a statistically significant correlation (Pearson's correlation coefficient γ=0.482, precurrence. In NSCLC patients treated by chemotherapy for recurrence, preoperative measurements of (18)F-FDG uptake may be a more powerful surrogate marker for predicting outcome when measured preoperatively at the primary tumor site rather than postoperatively at sites of recurrence. © 2013 Published by The Japanese Respiratory Society on behalf of The Japanese Respiratory Society.

  14. Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity

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    Lei Hu

    2016-05-01

    Full Text Available Long non-coding RNA (lncRNA CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively. It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03. Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04 and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01. Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively. Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.

  15. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

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    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi [Keio Univ., Tokyo (Japan). School of Medicine

    1997-02-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  16. XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer.

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    Mantang Qiu

    Full Text Available BACKGROUND: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3 Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC, while the conclusion is still conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs and hazard ratios (HRs and corresponding 95% confidence intervals (95% CIs were used to estimate the association strength. RESULTS: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696. This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564, and there was no difference between Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

  17. Treatment of platinum-resistant recurrent ovarian cancer using a "predictive molecule targeted routine chemotherapy" system

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-dong; WEI Feng-hua; ZHANG Yi; HE Shu-rong; YANG Li

    2009-01-01

    Background Correct drug selection, the key to successful chemotherapy, is one of the most difficult clinical decisions for the treatment of platinum-resistant recurrent ovarian cancer worldwide. The exact procedures for choosing drugs are undefined, currently relying on clinical trials and personal experience, which often results in disappointing outcomes. Here, we propose a new drug selection method, the "predictive molecule targeted routine chemotherapy", to choose relatively sensitive routine drugs and avoid relatively resistant routine drugs based on the specific predictive molecule expression of the individual tumor tissue.Methods From January 2004 to June 2008,26 cases of platinum-resistant recurrent ovarian cancer were prospectively recruited. Their routine chemotherapy drug choice was based on the expression of 6 predictive molecules (including p53) as determined by immunohistochemistry (the predictive molecule targeted routine chemotherapy group). A further 18 cases of platinum-resistant recurrent ovarian cancer were treated by experience and formed the control group. The response rate and the overall survival were compared between the two groups.Results The response rate to second-line chemotherapy was 28% in the control group and 77% in the predictive molecule targeted routine chemotherapy group (P=0.002). The response rate to third-line chemotherapy was 14% in the control group and 33% in the predictive molecule targeted routine chemotherapy group (P=0.268). The median overall survival of the predictive molecule targeted routine chemotherapy group (88 weeks) was significantly longer than the median overall survival of the control group (56 weeks) (P=0.0315).Conclusion The predictive molecule targeted routine chemotherapy is a new effective protocol for choosing drugs when treating platinum-resistant recurrent ovarian cancer.

  18. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study).

    Science.gov (United States)

    Cicènas, Saulius; Geater, Sarayut Lucien; Petrov, Petar; Hotko, Yevgeniy; Hooper, Gregory; Xia, Fan; Mudie, Nadejda; Wu, Yi-Long

    2016-12-01

    The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed following four cycles of platinum-based chemotherapy. Patients had stage IIIB/IV NSCLC, no known epidermal growth factor receptor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-based induction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing. Patients were randomized to receive blinded maintenance erlotinib 150mg/day ('early erlotinib') or placebo. Those who progressed on placebo received open-label erlotinib ('late erlotinib'); patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS). 643 patients were randomized to receive maintenance erlotinib (n=322) or placebo (n=321). As of March 23, 2015, 242 (75.2%) OS events had occurred with 'early erlotinib' versus 235 (73.2%) with 'late erlotinib'. Median OS was 9.7 and 9.5 months with 'early erlotinib' and 'late erlotinib', respectively (HR, 1.02, 95% CI: 0.85-1.22; log-rank p=0.82). No progression-free survival, objective response rate, or disease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second-line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%) from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previous trials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs. OS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with the established safety profile of erlotinib. Thus

  19. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

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    Dimitra T Stefanou

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780 and one resistant (A2780/C30 to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs from OC patients, sensitive (n = 7 or resistant (n = 4 to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9 were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05. Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03. Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05. We conclude

  20. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.

    Science.gov (United States)

    Pinato, David J; Graham, Janet; Gabra, Hani; Sharma, Rohini

    2013-04-01

    Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

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    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  2. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  3. Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer

    Science.gov (United States)

    Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; Chang, Jianhua; Wei, Qingyi

    2016-01-01

    The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings. PMID:26993769

  4. Can Aidi injection restore cellular immunity and improve clinical efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy? A meta-analysis of 17 randomized controlled trials following the PRISMA guidelines.

    Science.gov (United States)

    Xiao, Zheng; Wang, Chengqiong; Sun, Yongping; Li, Nana; Li, Jing; Chen, Ling; Yao, Xingsheng; Ding, Jie; Ma, Hu

    2016-11-01

    Aidi injection is an adjuvant chemotherapy drug commonly used in China. Can Aidi injection restore the cellular immunity and improve the clinical efficacy in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy? There is a lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about the clinical efficacy and cellular immunity of Aidi injection plus platinum-based chemotherapy for NSCLC in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China biological medicine database (CBM) (established to June 2015), Cochrane Central Register of Controlled Trials (CCRCT) (June 2015), Chinese clinical trial registry, and US-clinical trials (June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the patient intervention control group outcomes principles and synthesized the data by meta-analysis. Seventeen (RCTs) with 1390 NSCLC patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as follows: 1.26 (1.12, 1.42) and 1.11(1.04, 1.17). The merged standardized mean difference (SMD) values and their 95% CI of meta-analysis for the percentage of CD3T cells, CD4T cells, CD8T cells, natural killer (NK) cells, and CD4/CD8 T cell ratio were as follows: 1.41, (0.89, 1.92), 1.59, (1.07, 2.11), 0.85, (0.38, 1.33), 1.64 (0.89, 2.39) and 0.91, (0.58, 1.24). Compared with platinum-based chemotherapy alone, all differences were statistically significant. These results might be overestimated or underestimated. Aidi injection plus platinum-based chemotherapy can improve the clinical efficacy of patients with NSCLC. Aidi

  5. Relationship of Insulin-like Growth Factor Receptor Single Nucleotide 
Polymorphism (SNP with Platinum-based Chemotherapy Outcomes in Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusheng CHEN

    2012-02-01

    Full Text Available Background and objective It has been proven that the insulin-like growth factor 1 receptor (IGF-1R gene is an important regulator of many aspects of growth, differentiation, and development. The insulin-like growth factor 2 receptor (IGF-2R gene is a negative mediator for carcinogenesis. The aim of this study is to investigate the relationship of IGF-1R+1013(G/A and IGF-2R+1619(G/A single nucleotide polymorphism (SNP with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC. Methods A total of 132 patients with NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated after four cycles of chemotherapy. IGF-1R+1013(G/A and IGF-2R+1619(G/A were genotyped using polymerase chain reaction-restrictive fragment length polymorphism. The relationship between IGF-1R+1013(G/A and IGF-2R+1619(G/A genotypes and the clinical benefit rate, as well as the median survival time (MST, was analyzed. Results No significant association was found between IGF-1R+1013(G/A and IGF-2R+1619(G/A polymorphisms with clinical benefit (P>0.05. Further, we found that the two SNPs could not work together (P=0.975. The MST of patients with IGF-1R+1013(G/A genotypes with A allele (GA+AA was significantly shorter than that of GG genotype carriers (P=0.017. There was no significant difference in MST in patients with IGF-2R+1619(G/A A allele (GA+AA carrier and GG genotype carrier (P=0.575. The two SNPs showed a synergistic effect on MST. Patients who carried a mutant allele A of IGF-1R+1013(G/A and a mutant allele A of IGF-2R+1619(G/A had a MST of 12 months, which was significantly shorter than that of patients with other genotypes (P<0.05. Estimation by the Cox proportional hazards model showed that IGF-1R+1013(G/A polymorphism is an independent prognostic factor (P=0.020, and IGF-1R+1013(G/A polymorphism in combination with IGF-2R +1619(G/A polymorphism is an independent prognostic factor in advanced

  6. Chemotherapy-Induced Cognitive Impairment: A Novel Prospective Study of the Cognitive Effects of Platinum Taxane-Based Chemotherapy in Ovarian Cancer Patients

    Science.gov (United States)

    2016-09-01

    interested in participating in the MRI neuro -testing, but had to be excluded due to being left-handed (this study is only including right-handed...participants at this time). Enrollment is ongoing. 15. SUBJECT TERMS: OVARIAN CANCER,COGNITIVE IMPAIRMENT,CHEMOTHERAPY, CANCER 16. SECURITY CLASSIFICATION OF: 17

  7. Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mathieu D. Saint-Pierre

    2015-01-01

    Full Text Available Introduction. Malignant pleural mesothelioma (MPM is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P=0.35. Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P=0.97. Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

  8. A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy.

    Science.gov (United States)

    Scagliotti, Giorgio; Nishio, Makoto; Satouchi, Miyako; Valmadre, Giuseppe; Niho, Seiji; Galetta, Domenico; Cortinovis, Diego; Benedetti, Fabio; Yoshihara, Eiji; Makris, Lukas; Inoue, Akira; Kubota, Kaoru

    2016-10-01

    TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer. As this agent has shown activity greater than cisplatin in small cell lung cancer xenograft mouse models, the objective of this study was to evaluate TAS-102 in the second-line treatment of small cell lung cancer. This was a multicenter, open-label, two-arm, randomized phase 2 study designed to compare oral TAS-102 (35mg/m(2)/dose twice daily) versus control (topotecan or amrubicin). Patients requiring second-line chemotherapy for treatment of small cell lung cancer, either refractory or sensitive to frontline platinum-based chemotherapy, were enrolled. Eighteen patients were enrolled. Eight of nine patients receiving TAS-102 discontinued treatment due to progressive disease and one patient died due to clinical progression during the safety follow-up. Unplanned interim futility considerations were made, and the study was terminated early because it was unlikely that superiority of TAS-102 versus comparator could be demonstrated. Six control patients discontinued therapy due to progressive disease and one due to an adverse event. Median progression-free survival was 1.4 months (range 0.9-1.8) versus 2.7 months (range 1.0-6.8) for TAS-102 and control, respectively, with a hazard ratio of 3.76 (80% CI, 1.68-8.40) favoring control. The most common adverse events with TAS-102 were neutropenia, diarrhea, anemia, anorexia, and fatigue, each in three patients. TAS-102 showed no evidence of activity in second-line small cell lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Wen-Feng Fang; Yu-Xiang Ma; Li Zhang; Yuan-Yuan Zhao; Ying Guo; Cong Xue; Zhi-Huang Hu; Yan Huang; Hong-Yun Zhao; Jing Zhang; Xuan Wu

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials-involving 11,456 adult patients in 32 arms-were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797,P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936,P < 0.001) but was not statisticaly significant in the trials in predominantly Caucasian populations (r = 0.116,P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

  10. Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy.

    Science.gov (United States)

    Tambo, Yuichi; Hosomi, Yukio; Sakai, Hiroshi; Nogami, Naoyuki; Atagi, Shinji; Sasaki, Yasutsuna; Kato, Terufumi; Takahashi, Toshiaki; Seto, Takashi; Maemondo, Makoto; Nokihara, Hiroshi; Koyama, Ryo; Nakagawa, Kazuhiko; Kawaguchi, Tomoya; Okamura, Yuta; Nakamura, Osamu; Nishio, Makoto; Tamura, Tomohide

    2017-04-01

    Objectives To determine the recommended dose and efficacy/safety of docetaxel combined with resminostat (DR) in non-small cell lung cancer (NSCLC) patients with previous platinum-based chemotherapy. Materials and Methods A multicenter, open-label, phase I/II study was performed in Japanese patients with stage IIIB/IV or recurrent NSCLC and prior platinum-based chemotherapy. The recommended phase II dose was determined using a standard 3 + 3 dose design in phase I part. Resminostat was escalated from 400 to 600 mg/day and docetaxel fixed at 75 mg/m(2). In phase II part, the patients were randomly assigned to docetaxel alone (75 mg/m(2)) or DR therapy. Docetaxel was administered on day 1 and resminostat on days 1-5 in the DR group. Treatment was repeated every 21 days until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Results A total of 117 patients (phase I part, 9; phase II part, 108) were enrolled. There was no dose-limiting toxicity in phase I part; the recommended dose for resminostat was 600 mg/day with 75 mg/m(2) of docetaxel. In phase II part, median PFS (95% confidence interval [CI]) was 4.2 (2.8-5.7) months with docetaxel group and 4.1 (1.5-5.4) months with DR group (hazard ratio [HR]: 1.354, 95% CI: 0.835-2.195; p = 0.209). Grade ≥ 3 adverse events significantly more common with DR group than docetaxel group were leukopenia, febrile neutropenia, thrombocytopenia, and anorexia. Conclusion In Japanese NSCLC patients previously treated with platinum-based chemotherapy, DR therapy did not improve PFS compared with docetaxel alone and increased toxicity.

  11. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek;

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  12. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

    Directory of Open Access Journals (Sweden)

    Ramon Andrade de Mello

    Full Text Available BACKGROUND: The use of cetuximab in combination with platinum (P plus 5-fluorouracil (F has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN. We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS, progression-free-survival (PFS, overall response rate (ORR and the treatment toxicity profile in a retrospective cohort. PATIENTS AND METHODS: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. RESULTS: The median patient age was 53 (37-78 years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316 and PFS of 8 months (CI 95%, 6.051-9.949. The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%, skin rash (3.8% and mucosistis (3.8%. CONCLUSIONS: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

  13. Modelling and sensitivity analysis of urinary platinum excretion in anticancer chemotherapy for the recovery of platinum

    DEFF Research Database (Denmark)

    Folens, Karel; Mortier, Séverine Thérèse F C; Baeten, Janis

    2016-01-01

    Platinum (Pt) based antineoplastics are important in cancer therapy. To date the Pt which is urinary excreted by the patients ends up in wastewater. This is disadvantageous from both an economic as from an ecological point of view because Pt is a valuable material and the excretion products are t...

  14. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

    Directory of Open Access Journals (Sweden)

    Yang CJ

    2016-03-01

    study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417 but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007. Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083 and a trend for better OS2 than those without pemetrexed treatment.Conclusion: Pemetrexed-based platinum chemotherapy may be the most optimal therapy in acquired resistance to gefitinib. Further prospective randomized controlled study is needed urgently. Keywords: epidermal growth factor receptor, gefitinib, acquired resistance, pemetrexed, chemotherapy

  15. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer.

    Science.gov (United States)

    Arrieta, Oscar; Cardona, Andrés Felipe; Corrales, Luis; Campos-Parra, Alma Delia; Sánchez-Reyes, Roberto; Amieva-Rivera, Eduardo; Rodríguez, July; Vargas, Carlos; Carranza, Hernán; Otero, Jorge; Karachaliou, Nikki; Astudillo, Horacio; Rosell, Rafael

    2015-02-01

    In non-small cell lung cancer (NSCLC), the association between common EGFR mutations (Del EX19/L858R) with EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been well established. However, this has not been investigated for rare EGFR mutations or their impact on treatment response and outcome to EGFR TKIs (primary objective) and chemotherapy (secondary objective). In an observational prospective cohort, we analyzed 188 NSCLC patients from Mexico, Colombia and Costa Rica with EGFR mutations. As a first line of treatment, 66.5% received platinum-based chemotherapy. All patients received TKIs in first-line treatment or after progression to chemotherapy. The clinical-pathological characteristics as well as the f of common and rare EGFR mutations associated with treatment response were analyzed. Of all patients, 79.5% had common and 20.5% had rare EGFR mutations. Lepidic and acinar adenocarcinomas were associated with common EGFR mutations (p=0.010). Patients with common EGFR mutations had higher response rates to EGFR-TKIs than those who had rare EGFR mutations (63.8 vs 32.4%, p<0.001). Women had increased progression-free survival (PFS) to EGFR-TKIs than men (16.4 vs 9.5 months, p=0.02). The median PFS and overall survival (OS) were better in patients with common EGFR mutations (15.5 vs 3.9 months, p<0.001; and 37.3 vs 17.4 months, p<0.001) respectively. Our findings suggested that only patients with rare EGFR mutations could receive platinum-based chemotherapy as a first-line treatment, due to their low response rates and short PFS in response to EGFR-TKIs. Consequently, EGFR-TKIs could be reserved as a second- or third-line treatment. In patients with EGFR mutations, women have better PFS to EGFR-TKIs than men, and rare EGFR mutations are more frequent in high grade adenocarcinomas than in low grade tumors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    Science.gov (United States)

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

  17. A feasibility study of the use of saliva as an alternative to leukocytes as a source of DNA for the study of Pt-DNA adducts in cancer patients receiving platinum-based chemotherapy.

    Science.gov (United States)

    Taylor, Sarah E; Wood, Joanna P; Thomas, Anne L; Jones, George D D; Reid, Helen J; Sharp, Barry L

    2014-12-01

    This note presents a comparison of the use of saliva versus leukocytes for the determination of Pt-DNA adducts obtained from patients undergoing platinum-based chemotherapy. Samples of both blood and saliva were taken pre- and post-treatment and were analysed via sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) to determine the level of Pt-DNA adducts formed. As expected, significant inter-patient variability was seen; however, a lack of correlation between the levels of adducts observed in saliva and blood samples was also observed (Pearson correlation coefficient r = -0.2598). A high yield of DNA was obtained from saliva samples, but significant difficulties were experienced in obtaining patient adherence to the saliva sampling procedure. In both leukocyte and saliva samples, not only was Pt from previous chemotherapy cycles detected, but the rapid appearance of Pt in the DNA was noted in both sample types 1 h after treatment.

  18. Ototoxicity monitoring in children treated with platinum chemotherapy.

    Science.gov (United States)

    Brooks, Beth; Knight, Kristin

    2017-07-24

    To review the prevalence, mechanisms, clinical presentation, risk factors and implications of platinum-induced ototoxicity in paediatric cancer patients based on published evidence, discuss options for monitoring hearing in young children during treatment and review long-term follow-up guidelines. Narrative literature review. Children treated with cisplatin are at high risk of hearing loss and early, accurate identification of ototoxicity is important for medical decision making and hearing rehabilitation. Challenges of monitoring hearing in young children during cancer treatment and options for monitoring hearing are discussed. Hearing loss has important consequences for the survivors of childhood cancer including communication, learning, cognition and quality of life. Due to the presentation and configuration of ototoxic hearing loss, the test frequencies that are prioritised and the sequence of testing may differ from standard paediatric hearing evaluations. Hearing should be monitored during treatment and after completion of therapy.

  19. The Discovery, Use and Impact of Platinum Salts as Chemotherapy Agents for Cancer, vol. 30.

    OpenAIRE

    2007-01-01

    Proposed by Dr Mark Walport (Wellcome Trust) this Seminar examined the discovery, use and impact of platinum salts as chemotherapy agents for cancer. Organized with the assistance of Professor Paul Andrews (St George’s Hospital Medical School) and Dr Tony Woods (Wellcome Trust) and chaired by Professor Sir Kenneth Calman (Durham) the Seminar discussed the serendipitous emergence of platinum salts as widely used anticancer agents from a chance observation in a microbiology laboratory; through ...

  20. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    Science.gov (United States)

    Heigener, David F; Pereira, José Rodrigues; Felip, Enriqueta; Mazal, Juraj; Manzyuk, Lyudmila; Tan, Eng Huat; Merimsky, Ofer; Sarholz, Barbara; Esser, Regina; Gatzemeier, Ulrich

    2015-06-01

    The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.

  1. Anti-tumor activity of an anti-DR5 monoclonal antibody, TRA-8, in combination with taxane/platinum-based chemotherapy in an ovarian cancer model.

    Science.gov (United States)

    Bevis, Kerri S; McNally, Lacey R; Sellers, Jeffery C; Della Manna, Deborah; Londoño Joshi, Angelina; Amm, Hope; Straughn, J Michael; Buchsbaum, Donald J

    2011-04-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis via binding to death receptors and enhances the anti-tumor effect of conventional cancer therapies. We evaluated the efficacy of TRA-8, an agonistic antibody to DR5, combined with docetaxel and carboplatin in vitro in an intraperitoneal (IP) ovarian cancer model. Luciferase positive ES2 cells (ES2H) were treated in 96 well plates with TRA-8, carboplatin, docetaxel, and combination therapy. Cell viability was assessed using ATP-lite assay. Apoptosis was confirmed via Western blot analysis. ES2H cells were injected IP into female athymic nude mice. Animals were sorted based on bioluminescent signal with the following treatments: 1) untreated; 2) TRA-8 alone; 3) docetaxel+carboplatin; and 4) docetaxel+carboplatin+TRA-8. Animals receiving TRA-8 antibody were injected IP with 200 μg of TRA-8 twice weekly until death. Animals receiving docetaxel+carboplatin were injected IP with 5mg/kg and 15 mg/kg respectively every 3 weeks until death. Animals were assessed for tumor burden using bioluminescence imaging and overall survival. Combination therapy reduced viability of ES2H cells in vitro over single agent therapy. Tumor burden was lowest in the chemotherapy+TRA-8 group at days 23 (pTRA-8 group (41 days) compared to the chemotherapy only group (34 days) and control group (27 days) as determined by Kaplan-Meier analysis (pTRA-8 reduced cell-viability via activation of apoptotic pathways, reduced tumor burden and improved survival in this ovarian cancer model. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen.

    Science.gov (United States)

    Soulières, Denis; Aguilar, Jose Luis; Chen, Eric; Misiukiewicz, Krzysztof; Ernst, Scott; Lee, Hyun Jung; Bryant, Katherine; He, Shuang; Obasaju, Coleman K; Chang, Shao-Chun; Chin, Steve; Adkins, Douglas

    2016-01-14

    Cetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab). This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations. Patients with previously untreated locoregionally recurrent and/or metastatic SCCHN were randomly assigned to receive the same dose of US commercial cetuximab (Arm A) or BI-manufactured cetuximab (Arm B), each in combination with cisplatin or carboplatin plus 5-FU. The primary outcome was all-grade, all-cause treatment-emergent adverse events (TEAEs). The majority of patients experienced ≥ 1 TEAE, regardless of causality (Arm A: 75/77 patients, 97.4%; Arm B: 68/71 patients, 95.8%). TEAEs with the highest incidence included nausea, fatigue, and hypomagnesemia in both arms. The absolute risk difference between the two arms for patients experiencing at least one adverse event (AE) was 0.029 (p = 0.281, 95% confidence interval [CI]: -0.024, 0.082) for AEs regardless of causality and 0.005 (p = 0.915, 95% CI: -0.092, 0.103) for AEs possibly related to study drug. There were no significant differences between the two arms in the incidence of acneiform rash, cardiac events, infusion reactions, or hypomagnesemia. Overall survival, progression-free survival, and overall response rates were similar in the two arms. There were no clinically meaningful differences in safety between US commercial cetuximab and BI-manufactured cetuximab in combination with platinum-based therapy with 5-FU in patients with locoregionally recurrent and/or metastatic SCCHN. The use of US commercial cetuximab in this combination chemotherapy regimen did not result in any unexpected safety signals. The

  3. Sequential treatment of tyrosine kinase inhibitor and platinum-based doublet chemotherapy on EGFR mutant non-small cell lung cancer: a meta-analysis of randomized controlled clinical trials

    Science.gov (United States)

    Qiao, Lifen; Wang, Jin; Long, Guoxian; Jiang, Yueqiang

    2017-01-01

    There is debate surrounding which treatment is superior in overall survival (OS) rates in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC); first-line tyrosine kinase inhibitor (TKI) followed by second-line platinum-based doublet chemotherapy (PCT), or the reverse sequence. Cross treatment of first- and second-line TKI and PCT makes it difficult to deduce which sequence (TKI-PCT or PCT-TKI) is better for OS. Using the keywords “lung cancer” and “EGFR” we identified clinical trials within the PubMed database which were published between January 2006 and November 2016. Basic characteristics and OS with hazard ratio and 95% confidence intervals were searched and analyzed. In total, 457 articles were reviewed and nine clinical trials with 1,876 patients were of sufficient quality for further analysis. Fixed effects models were performed to pool the data in this meta-analysis. All nine studies were open-labeled, multicenter, Phase III randomized controlled clinical trials. The pooled hazard ratio was 0.96 (95% confidence interval: 0.84–1.10) for OS between first-line TKI followed by second-line PCT compared to the reverse sequence. No statistically significant heterogeneity (I2=0, P=0.553) nor publication bias (Egger’s P=0.991) was observed among these studies. In conclusion, there was no OS benefit between first-line TKI followed by second-line PCT compared to the reverse sequence in EGFR mutant NSCLC patients. Chemotherapy was still useful and irreplaceable for the treatment of NSCLC, especially for those patients with EGFR unavailable for testing. PMID:28280362

  4. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Xiao HQ

    2016-03-01

    Full Text Available Huai-Qing Xiao,1 Rong-Hua Tian,2 Zhi-Hao Zhang,1 Kai-Qi Du,1 Yi-Ming Ni3 1Department of Cardiothoracic Surgery, Zhejiang Corps Hospital, Chinese People’s Armed Police Force, Jiaxing, Zhejiang Province, People’s Republic of China; 2Department of Respiratory, Affiliated Haian People’s Hospital of Nantong University, Haian, Jiangsu, People’s Republic of China; 3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Purpose: To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC through a trial-level meta-analysis. Methods: Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library. All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR, progression-free survival (PFS, and overall survival (OS were extracted and analyzed using comprehensive meta-analysis software (version 2.0. Results: A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%, with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01 but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084 in advanced nonsquamous NSCLC patients. Conclusion: Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our

  5. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    Science.gov (United States)

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  6. Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

    Directory of Open Access Journals (Sweden)

    Hill Andrew

    2010-08-01

    Full Text Available Abstract Background Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Methods Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Results Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6 and 72% of muscles (n = 22 on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8 and 13% of muscles (n = 32 on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14 or muscles (n = 56 tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7 and 32% of muscles (n = 32 on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22 and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6. Conclusions Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve

  7. Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Tappenden, Paul; Harnan, Sue; Ren, Shijie; Thokala, Praveen; Wong, Ruth; Mukuria, Clara; Green, Clare; Pledge, Simon; Tidy, John

    2017-01-01

    As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaparib (AstraZeneca) to submit evidence on the clinical and cost effectiveness of olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum-sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy. The Evidence Review Group (ERG) produced a critical review of the evidence contained within the company's submission (CS) to NICE. The clinical evidence related to one phase II, double-blind randomised controlled trial that recruited 265 patients with PSR serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib 400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR] 0.35; 95 % confidence interval [CI] 0.25-0.49, p group (HR 0.88; 95 % CI 0.64-1.21; p = 0.44) or the BRCAm subgroup (0.73; 95 % CI 0.45-1.17; p = 0.19), though treatment switching may have confounded results. The exclusion of data from sites allowing crossover resulted in an HR for overall survival (OS) of 0.52 (95 % CI 0.28-0.97, p = 0.039) in the BRCAm group. Health-related quality-of-life measures were not significantly different between groups. All post hoc exploratory outcomes (time to treatment discontinuation/death, time to first subsequent therapy/death, and time to second subsequent therapy/death) were statistically significantly better in the olaparib arm in the whole population and the BRCAm subgroup analyses. Adverse events were more frequent for olaparib but were largely minor or manageable. The company's semi-Markov model assessed the cost effectiveness of olaparib versus routine surveillance in patients with BRCAm PSR OC from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a

  8. Platinum(IV) Carboxylate Prodrug Complexes as Versatile Platforms for Targeted Chemotherapy.

    Science.gov (United States)

    Ong, Jun Xiang; Yap, Siew Qi; Wong, Daniel Yuan Qiang; Chin, Chee Fei; Ang, Wee Han

    2015-01-01

    Kinetically-inert Pt(IV) carboxylate complexes have emerged in recent years as candidates for the development of next-generation platinum anticancer drugs. Being native prodrugs of clinically-important Pt(II) chemotherapeutic agents, the Pt(IV) scaffold can be exploited to incorporate additional functionalities while keeping the Pt(II) pharmacophore intact. This mini-review examines recent work performed to illuminate the mechanism of Pt(IV) prodrug activation and their use as versatile platforms for targeted chemotherapy.

  9. Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise

    2015-01-01

    BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment......, and if it persists after treatment completion, has a negative impact on quality of life (QoL). RESULTS: Symptoms of CIPN are sensory, like pain, numbness, and tingling, typically located in the hands and feet. For oxaliplatin, there is an acute form of CIPN, resulting in paraesthesias in the mouth and throat during......-induced neuropathy is irreversible, CIPN induced by taxanes may persist for several years in about 30% of patients. Evidence from the literature is suggestive that CIPN is likely to be negatively associated with QoL. No agents have been identified to be recommended for the prevention of CIPN. For treatment of CIPN...

  10. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial.

    Science.gov (United States)

    Bamias, A; Gibbs, E; Khoon Lee, C; Davies, L; Dimopoulos, M; Zagouri, F; Veillard, A-S; Kosse, J; Santaballa, A; Mirza, M R; Tabaro, G; Vergote, I; Bloemendal, H; Lykka, M; Floquet, A; Gebski, V; Pujade-Lauraine, E

    2017-08-01

    In the open-label randomized phase III AURELIA trial, adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) significantly improved progression-free survival and response rate versus chemotherapy alone, but not overall survival (OS). We explored the effect of bevacizumab use after disease progression (PD) in patients randomized to chemotherapy alone. In AURELIA, 361 women with PROC were randomized to chemotherapy alone or with bevacizumab. Patients initially randomized to chemotherapy were offered bevacizumab after PD. Post hoc analyses assessed efficacy and safety in three subgroups: chemotherapy alone, chemotherapy followed by bevacizumab after PD, and chemotherapy plus bevacizumab at randomization. Of the 182 patients randomized to chemotherapy alone, 72 (40%) received bevacizumab after PD and 110 (60%) never received bevacizumab. There were no significant differences in patient and disease characteristics between these subgroups at baseline or the time of PD. Compared with patients never receiving bevacizumab, the risk of death was significantly reduced in patients receiving bevacizumab either upfront with chemotherapy [hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.52-0.90] or after PD (HR = 0.60, 95% CI 0.43-0.86). The tolerability of bevacizumab was similar with administration upfront or after PD. Post-PD bevacizumab use may have confounded OS results in AURELIA. In these exploratory analyses of non-randomized subgroups, bevacizumab use, either with chemotherapy or after PD on chemotherapy alone, improved OS compared with no bevacizumab. Combining bevacizumab with chemotherapy at first appearance of platinum resistance maximises the likelihood of patients receiving this active treatment for PROC. ClinicalTrials.gov: NCT00976911.

  11. TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study

    Directory of Open Access Journals (Sweden)

    Markowska Janina

    2008-01-01

    Full Text Available Abstract Background Taxane-platinum therapy (TP has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC. Methods We compared the effectiveness of PC/PAC (n = 253 and TP (n = 199 with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+] and without TP53 accumulation [TP53(-]. Results The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+, and not in the TP53(- group. In the TP53(+ group taxane-platinum therapy enhanced the probability of complete remission (p = .018, platinum sensitivity (p = .014, platinum highly sensitive response (p = .038 and longer survival (OS, p = .008. Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+ group. In the TP53(- group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010. However, in the TP53(- group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077. Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation. Conclusion Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+ tumors or older

  12. Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives.

    Science.gov (United States)

    Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise

    2015-05-01

    Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment, and if it persists after treatment completion, has a negative impact on quality of life (QoL). Symptoms of CIPN are sensory, like pain, numbness, and tingling, typically located in the hands and feet. For oxaliplatin, there is an acute form of CIPN, resulting in paraesthesias in the mouth and throat during or shortly after the infusion triggered by exposure to cold. Risks factors for CIPN include preexisting neuropathy, either from treatment with other neurotoxic agents, or from comorbid conditions. The incidence of CIPN is related to dose per cycle, cumulative dose, and duration of infusion. While cisplatin-induced neuropathy is irreversible, CIPN induced by taxanes may persist for several years in about 30% of patients. Evidence from the literature is suggestive that CIPN is likely to be negatively associated with QoL. No agents have been identified to be recommended for the prevention of CIPN. For treatment of CIPN, the best available data supports a moderate recommendation for treatment with duloxetine and evidence is inconclusive regarding the use of tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine. Research is still needed to predict which patients are at high risk of developing CIPN during treatment and in whom CIPN will persist after completion of chemotherapy.

  13. ERCC1和XPD基因SNPs与晚期NSCLC含铂类药物化疗敏感性的关系%Association between polymorphisms of ERCC1 and XPD and sensitivity to platinum-based chemotherapy in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张胜利; 张增利; 施敏骅

    2013-01-01

    Objective To investigate whether SNPs of ERCCKC118T) and XPD(Lys751Gln) were associated with the sensitivity of non-small-cell lung cancer ( NSCLC) to platinum-based chemotherapy in the patients with advanced NSCLC. Methods Polymorphisms of ERCC1 and XPD were detected by PCR-restrictive fragment length polymorphism (PCR-RFLP) method in 78 cases. Results No association was detected between polymorphisms of ERCC1 and XPD and age, sex, histologic type,ECOG performance status,smoking history and clinical stage of tumor. The difference of clinical response was not found among age, sex, ECOG performance status and smoking history (P>0. 05). The polymorphic genotypes of ERCCl (C118T) were related to the sensitivity to platinum-based chemotherapy. Conclusion The patients carrying at least 1 T allele(T/T+C/T) may be taken as a marker to predict the sensitivity of NSCLC to platinum-based chemotherapy.%目的 探讨切除修复交叉互补基因1(ERCC1)第118位密码子(C118T)和着色性干皮病基因D(XPD)第751位密码子(Lys751Gln)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者含铂类药物化疗疗效的关系.方法 用PCR-限制性片段长度多态性(PCR-RFLP)技术检测78例NSCLC患者的ERCC1 (C118T)和XPD(Lys751Gln)基因型.结果 ERCC1(C118T)、XPD(Lys751Gln) SNPs不受年龄、性别、吸烟史、临床分期、体力状况评分(ECOG)和病理类型影响;ERCC1 (C118T)中不同的年龄、性别、吸烟史和ECOG评分之间化疗疗效差异无统计学意义.ERCC1(C118T) SNPs与含铂类药物化疗疗效有关.结论 含有T等位基因可作为预测晚期NSCLC患者铂类药物化疗敏感性的预测指标.

  14. A research of platinum-based dual drugs versus single agent chemotherapy for elderly and comorbidity patients with advanced non-small cell lung cancer%存在内科合并症的老年晚期非小细胞肺癌患者一线含铂双药与单药方案化疗的对照研究

    Institute of Scientific and Technical Information of China (English)

    张琼妍; 李大鹏; 陶敏

    2012-01-01

    目的 探讨含铂双药与第3代化疗药物单药方案化疗在有内科合并症的老年晚期非小细胞肺癌(NSCLC)患者中的疗效和安全性.方法 回顾性分析150例有内科合并症(依据察尔森指数筛选)经细胞学或病理组织学确诊的老年晚期NSCLC患者.按照接受一线化疗方案分为第3代化疗药物单药组(28例)和含铂双药组(122例),比较两组的疗效及不良反应.结果 所有患者均可评价疗效.单药组获PR 6例(21.4%),SD 2例(7.1%),PD 20例(71.4%),有效率为21.4%;双药组获PR 48例(39.3%),SD 10例(8.2%),PD 64例(52.5%),有效率为39.3%,两组有效率差异无统计学意义(P>0.05).单药组和双药组的中位无进展时间(PFS)分别为5.0个月和7.0个月(P =0.617),中位总生存期(OS)分别为7.4个月和10.7个月(P =0.473).经年龄、ECOG评分和察尔森指数1~2分分层后发现,单药组与双药组的PFS或OS差异均无统计学意义(P>0.05);而经察尔森指数3-4分分层后发现,单药组和双药组的中位PFS分别为3.5个月和8.3个月(P=0.001),中位OS为5.0个月和8.3个月(P=0.019).不良反应主要包括中性粒细胞减少、贫血、血小板减少和恶心呕吐,单药组不良反应基本为1~2级,双药组3~4级不良反应发生率较单药组高.结论 含铂双药方案一线治疗有内科合并症的老年晚期NSCLC的疗效与第3代化疗药物单药方案类似,而在察尔森指数3~4分患者中前者远期疗效更好,但总体不良反应发生率略高.%Objective To investigate the efficacy and toxicity of single agent and platinum-based dual drugs chemotherapy for elderly and comorbidity patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 150 cases of elderly NSCLC patients with cytological or pathological diagnosis were retrospectively reviwed. Doublet chemotherapy group was treated with platinum-based dual drugs, and single agent chemotherapy group was treated with the third

  15. Chemical Imaging of Platinum-Based Drugs and their Metabolites.

    Science.gov (United States)

    Liu, Xin; Hummon, Amanda B

    2016-12-05

    Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically. Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) is combined with an on-tissue chemical derivatization using diethyldithiocarbamate (DDTC). DDTC abstracts the Pt atom to generate ionizable complexes that can be imaged by MALDI MSI. We demonstrate that Pt drugs and their metabolites can be specifically imaged. This approach was successfully applied to map the penetration and metabolism of oxaliplatin in hyperthermic intraperitoneal chemotherapy (HIPEC)-like treated 3D colorectal tumor mimics. The distribution of cisplatin and carboplatin was mapped in additional 3D tumor mimics. We demonstrate that the approach can also be used to image the distribution of copper ions in cells. This method has the potential to be used to evaluate the penetration and distribution of a wide range of compounds.

  16. The pharmacogenomics of platinum chemotherapy in non-small cell lung cancer%非小细胞肺癌铂类化疗药物基因组学研究

    Institute of Scientific and Technical Information of China (English)

    崔佳佳; 尹继业

    2014-01-01

    Platinum-based chemotherapy is one of the major treatment methods for non-small-cell lung cancer (NSCLC), however, the therapeutic efficiency varies largely among different pa-tients.Genetic variation is one of the most important factors influencing NSCLC patients platinum-based chemotherapy, lots of gene mutations related to DNA damage and repair, drug metabolism and detoxification, cell cycle and apoptosis, drug transporter and membrane receptor were associated with response to platinum-based chemotherapy.In this review, the recent progress of pharmaco-genomics of platinum chemotherapy in NSCLC was systematically summarized, and also the possibility of establishing a pharmacogenomics model for accurately predicting platinum-based chemotherapy efficacy of NSCLC patients will be discussed.%基于铂类的联合化疗是当前非小细胞肺癌(non-small-cell lung cancer,NSCLC)治疗的主要途径之一,而不同患者的临床疗效差异较大。遗传因素是影响 NSCLC 铂类化疗疗效的重要因素之一,大量 DNA损伤与修复、药物代谢与解毒、细胞周期和凋亡、药物转运体与膜受体相关基因的变异都可以影响 NSCLC 铂类化疗药物化疗敏感性。本文将对上述内容进行系统全面的总结,并探讨建立准确预测 NSCLC 铂类化疗疗效的药物基因组学模型的可能性。

  17. Meeting report on 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy.

    Science.gov (United States)

    Kelland, L R

    1999-10-01

    The platinum-based drugs, cisplatin and carboplatin, represent major agents in the chemotherapeutic treatment of a variety of types of cancer. Novel, "third-generation" agents aimed at broadening the clinical activity of this class of drug are currently undergoing clinical evaluation. These include oxaliplatin, ZD0473 and BBR3464. Clinical trials and preclinical studies are also being conducted with liposomal (SPI-077 and L-NDDP) and polymeric platinum complexes (linked to HPMA or albumin). Combination studies of cisplatin/carboplatin with other anticancer drugs such as gemcitabine and UCN-01 (7-hydroxystaurosporine) and agents designed to reduce platinum drug toxicities (e.g., BNP-7787, DIMESNA) are ongoing. Preclinically, there is interest in trans platinum complexes, terpyridine platinum(II) complexes and other metal-containing agents (ruthenium and gold).

  18. Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.

    Science.gov (United States)

    Chisaki, Yugo; Nakamura, Nobuhiko; Yano, Yoshitaka

    2017-01-01

    The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

  19. A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer.

    Science.gov (United States)

    Cuffe, Sinead; Bourredjem, Abderrahmane; Graziano, Stephen; Pignon, Jean-Pierre; Domerg, Caroline; Ezzalfani, Monia; Seymour, Lesley; Strevel, Elizabeth; Burkes, Ronald; Capelletti, Marzia; Jänne, Pasi A; Tsao, Ming-Sound; Shepherd, Frances A

    2012-06-01

    The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status. Node-negative patients were reclassified as T2a (>3-≤5 cm), T2b (>5-≤7 cm), T3 (>7 cm) or T ≤ 3 cm (≤3 cm, but other T2 characteristics). Of 538 eligible patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%) T≤3 cm were excluded to avoid confounding. KRAS mutations were detected in 104 of 390 patients (27%). T-size was prognostic for disease-free survival (p = 0.03), but borderline for overall survival (OS; p = 0.10), on multivariable analysis. Significant interaction between the prognostic value of KRAS and tumor size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10). There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69, [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09; interaction p = 0.05). Similar trends were observed in T2b to T3 patients with wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74; interaction p = 0.58). Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status.

  20. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Hilpert, Felix; Weber, Béatrice; Reuss, Alexander; Poveda, Andres; Kristensen, Gunnar; Sorio, Roberto; Vergote, Ignace; Witteveen, Petronella; Bamias, Aristotelis; Pereira, Deolinda; Wimberger, Pauline; Oaknin, Ana; Mirza, Mansoor Raza; Follana, Philippe; Bollag, David; Ray-Coquard, Isabelle

    2014-05-01

    In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

  1. Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

    Science.gov (United States)

    Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

    2017-05-01

    AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Nanocarriers for delivery of platinum anticancer drugs☆

    Science.gov (United States)

    Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

  3. Clinical progression of lobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer

    Institute of Scientific and Technical Information of China (English)

    Yu Peng; Jiangkui Liu; Qiang Lin

    2014-01-01

    The-platinum-based-combination-chemotherapy-has-become-one-of-the-major-modalities-in-anti-cancer-treatment.-After-the-first-line-chemotherapy,-many-patients-need-further-chemotherapy-because-of-recurrence-or-metastasis.-Lobaplatin-is-one-of-the-third-generation-platinum-drugs,and-this-article-briefly-reviews-the-clinical-progression-of-lobaplatin-in-combination-chemotherapy-for-patients-with-recurrence-or-metastatic-cancer.

  4. Platinum(iv) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy

    Science.gov (United States)

    Shi, Saige; Chen, Xiaolan; Wei, Jingping; Huang, Yizhuan; Weng, Jian; Zheng, Nanfeng

    2016-03-01

    Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(iv) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(iv) prodrug loading. Once injected into biological tissue, the Pt(iv) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(ii) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(ii) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(iv) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The

  5. XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性%Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    许崇安; 王小杰; 张晔; 李琳

    2011-01-01

    背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8%.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1%vs22.2%,OR=2.545,95%CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5%,明显高于携带至少1个Gln等位基因者(21.9%)(OR=0.336,95%CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4% vs 18.8%,OR=3.467,95%CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.%Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung

  6. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients.

    Science.gov (United States)

    Liu, Rong; Zeng, Ying; Zhou, Cheng-Fang; Wang, Ying; Li, Xi; Liu, Zhao-Qian; Chen, Xiao-Ping; Zhang, Wei; Zhou, Hong-Hao

    2017-12-01

    Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.

  7. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Sundstrøm, Stein; Kaasa, Stein;

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other....... Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30...... neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL...

  8. Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the Treatment of Metastatic Spermatocytic Seminoma with Extensive Rhabdomyosarcomatous Transformation.

    Science.gov (United States)

    Jeong, Yumun; Cheon, Jaekyung; Kim, Tae-Oh; Lim, Doo-Ho; Lee, Sunpyo; Cho, Young-Mi; Hong, Jun Hyuk; Lee, Jae Lyun

    2015-10-01

    A 52-year-old man was presented with a huge left testicular mass and palpable cervical lymphadenopathy with retroperitoneal lymph node enlargement on an abdominal computed tomography. A left radical orchiectomy and an ultrasound-guided neck node biopsy were performed. A pathological examination revealed spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a condition known to be highly resistant to platinum-based chemotherapy. The patient received four cycles of etoposide, ifosfamide and cisplatin (VIP) chemotherapy. A repeat computed tomography revealed a substantial regression consistent with a partial response. Retroperitoneal lymph node dissection was attempted, which revealed rhabdomyosarcoma; however, complete microscopic resection was not achieved. After surgery, the residual abdominal lymph node progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy was employed, which again achieved a partial response. Here, we present a first case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous transformation and multiple metastatic lymphadenopathies that showed a favorable response to platinum-based systemic chemotherapy.

  9. Differences Between Asymmetric cis and trans Platinum Complexes. Applications in Cancer Chemotherapy

    NARCIS (Netherlands)

    Pantoja López, Elena

    2005-01-01

    This thesis describes a variety of asymmetric cis- and trans-platinum(II) complexes. The major aim of this research has been the design of complexes with high antitumor activity that may overcome cisplatin resistance, and to establish a comparison between complexes with both geometries. These new ty

  10. Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Smoter, Marta; Waldstrøm, Marianne

    2014-01-01

    of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC...

  11. An Analysis on Prognosis of Locoregionally Advanced Nasopharyngeal Carcinoma Treated with IMRT and Platinum-based Chemotherapy%调强放射治疗联合铂类化疗治疗局部晚期鼻咽癌预后分析

    Institute of Scientific and Technical Information of China (English)

    郭文杰; 许建华; 卞秀华; 姜雪松; 郭业松; 王雪; 宗丹; 何侠

    2012-01-01

    [目的]评价调强放射治疗联合铂类化疗治疗不同亚组局部晚期鼻咽癌的预后.[方法]将181例连续收治经病理学确诊的初治局部晚期鼻咽癌分为3组,以局部扩展为主要特征的T3~4N0~1M066例,以区域淋巴结转移为主要特征的T1~2N2~3M0 42例及混合型T3~4N2~3M0 73例,均采用调强放射治疗合并以铂类为基础的诱导化疗及同步化疗.中位随访24个月.[结果]局部扩展型、区域淋巴结转移型和混合型2年局部区域控制率分别为92.3%、100%及97.2% (P=0.32);2年无远处转移生存率分别为91.1%,78.2%和76.3% (P=0.016);2年无进展生存率分别为86.7%,78.2%和77.0%(P=0.095).COX多因素分析示N分期是局部晚期鼻咽癌远处转移及疾病相关死亡的独立的危险因素(HR=2.99,95 %CI:1.65~5.44;HR=3.20,95%CI:1.58~6.49).[结论]在调强放疗联合铂类化疗的治疗背景下,局部及区域晚期鼻咽癌中N2~3亚组预相对较差,远处转移率及疾病相关死亡率上升.%[Purpose] To investigate the prognosis of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and platinum-based chemotherapy. [Methods] One hundred eighty-one patients with locally advanced nasopharyngeal carcinoma were retrospectively divided into three subgroups: locally advanced (T3-4N0-1M0) group(n =66), regionally advanced (T1-2N2-3M0)group (n= 42) and the mixed group(T3-4V2-3,M0)(n=73). The patients were all treated with definitive intensity-modulated radiotherapy and platinum-based chemotherapy with median follow-up of 24 months. [Results] The 2-year locoregional control (LRC) rate for locally advanced group,regionally advanced group,and the mixed type group was 92.3%, 100% and 97.2% respectively(P=0.32),the 2-year distant metastasis free survival(DMFS) rate was 91.1%,78.2% and 76.3% repectively (P=0.016),the 2-year progress free survival (PFS) rate was 86.7%,78.2% and 77

  12. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy.

    Science.gov (United States)

    Felip, Enriqueta; Hirsh, Vera; Popat, Sanjay; Cobo, Manuel; Fülöp, Andrea; Dayen, Charles; Trigo, José M; Gregg, Richard; Waller, Cornelius F; Soria, Jean-Charles; Goss, Glenwood D; Gordon, James; Wang, Bushi; Palmer, Michael; Ehrnrooth, Eva; Gadgeel, Shirish M

    2017-06-23

    In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL. Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL. In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Urinary excretion of platinum, arsenic and selenium of cancer patients from the Antofagasta region in Chile treated with platinum-based drugs

    Directory of Open Access Journals (Sweden)

    Román Domingo A

    2012-04-01

    Full Text Available Abstract Background Arsenic exposure increases the risk of non-cancerous and cancerous diseases. In the Antofagasta region in Chile, an established relationship exists between arsenic exposure and the risk of cancer of the bladder, lung and skin. Platinum-based drugs are first-line treatments, and many works recognise selenium as a cancer-fighting nutrient. We characterised the short-term urinary excretion amounts of arsenic, selenium and platinum in 24-h urine samples from patients with lung cancer and those with cancer other than lung treated with cisplatin or/and carboplatin. As - Se - Pt inter-element relationships were also investigated. Results The amounts of platinum excreted in urine were not significantly different between patients with lung cancer and those with other cancers treated with cisplatin, despite the significant variation in platinum amounts supplied from platinum-based drugs. In general, the analytical amounts of excreted selenium were greater than those for arsenic, which could imply that platinum favours the excretion of selenium. For other types of cancers treated with drugs without platinum, excretion of selenium was also greater than that of arsenic, suggesting an antagonist selenium-anti-cancer drug relationship. Conclusions Regards the baseline status of patients, the analytical amounts of excreted Se is greater than those for As, particularly, for cisplatin chemotherapy. This finding could imply that for over the As displacement Pt favours the excretion of Se. The analytical amounts of excreted Se were greater than those for As, either with and without Pt-containing drugs, suggesting an antagonist Se-anti-cancer drug relationship. However, it seemed that differences existed between As - Se - Pt inter-element associations in patients treated for lung cancer in comparison with those treated for cancer other than lung. Therefore, knowledge obtained in this work, can contribute to understanding the arsenic cancer

  14. Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer.

    Science.gov (United States)

    Husain, Amreen; Wang, Yan; Hanker, Lars C; Ojeda, Belén; Anttila, Maarit; Breda, Enrico; Vuylsteke, Peter; Pujade-Lauraine, Eric

    2016-09-01

    The randomized, open-label, phase 3 Avastin® Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial achieved its primary efficacy end point of significantly improved progression-free survival (PFS) in patients treated with bevacizumab in combination with chemotherapy (CT) compared with CT alone for platinum-resistant, recurrent ovarian cancer. Primary analyses were conducted via investigator assessment of PFS; to confirm primary results, an independent review committee (IRC) retrospectively assessed radiographic data. Per an amendment to the original study protocol, the IRC reviewed radiographic data from 298 (82.5%) patients in a blinded manner using the Response Evaluation Criteria in Solid Tumors (modified version 1.0). IRC-assessed PFS and concordance between the two assessments were evaluated. IRC assessment demonstrated that PFS was significantly prolonged for patients treated with CT+bevacizumab compared with CT alone (median, 8.1 vs. 3.9months; hazard ratio, 0.484; 95% confidence interval, 0.370-0.632; PAURELIA study. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Biomarkers to assess the efficiency of treatment with platinum-based drugs: what can metallomics add?

    Science.gov (United States)

    Araujo, Thiago de O; Costa, Lilian T; Fernandes, Janaina; Aucélio, Ricardo Queiroz; de Campos, Reinaldo Calixto

    2014-12-01

    Since the approval of cisplatin as an antineoplastic drug, the medical and the scientific communities have been concerned about the side effects of platinum-based drugs, and this has been the dose-limiting factor that leads to reduced treatment efficiency. Another important issue is the intrinsic or acquired resistance of some patients to treatment. Identifying proper biomarkers is crucial in evaluating the efficiency of a treatment, assisting physicians in determining, at early stages, whether or not the patient presents resistance to the drug, minimizing severe side effects, and allowing them to redirect the established course of chemotherapy. A great effort is being made to identify biomarkers that can be used to predict the outcome of the treatment of cancer patients with platinum-based drugs. In this context, the metallomic approach has not yet been used to its full potential. Since the basis of these drugs is platinum, the monitoring of biomarkers containing this metal should be the natural approach to evaluate treatment progress. This review intends to show where the research in this field stands and points out some gaps that can be filled by metallomics.

  16. Synthesis of nanosized platinum based catalyst using sol-gel process

    Science.gov (United States)

    Ingale, S. V.; Wagh, P. B.; Bandyopadhyay, D.; Singh, I. K.; Tewari, R.; Gupta, S. C.

    2015-02-01

    The nano-sized platinum based catalysts using high surface area silica support have been prepared by sol-gel method. Tetramethoxysilane (TMOS) diluted in methanol was hydrolyzed to form a porous silica gel. Platinum (2%) was loaded at sol state using platinum chloride solution. After gelation, the solvent from the gel pores was extracted at ambient temperature which resulted in porous silica matrix incorporated with nanosized platinum. X-ray diffraction studies indicated the presence of elemental platinum in the silica-platinum composites. Transmission electron microscopy of the platinum -silica composites revealed that nanosized platinum particles of about 5-10 nm are homogeneously dispersed in silica matrix. Chemisorptions studies showed high dispersion (more than 50%) of platinum on silica support with specific surface area of 400 m2/g which puts them as promising candidates as catalyst in heterogeneous reactions.

  17. Toxicity of platinum compounds.

    Science.gov (United States)

    Hartmann, Jörg Thomas; Lipp, Hans-Peter

    2003-06-01

    Since the introduction of platinum-based combination chemotherapy, particularly cisplatin, the outcome of the treatment of many solid tumours has changed. The leading platinum compounds in cancer chemotherapy are cisplatin, carboplatin and oxaliplatin. They share some structural similarities; however, there are marked differences between them in therapeutic use, pharmacokinetics and adverse effects profiles [1-4]. Compared to cisplatin, carboplatin has inferior efficacy in germ-cell tumour, head and neck cancer and bladder and oesophageal carcinoma, whereas both drugs seem to have comparable efficacy in advanced non-small cell and small cell lung cancer as well as ovarian cancer [5-7]. Oxaliplatin belongs to the group of diaminocyclohexane platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid [8,9]. Other platinum compounds such as oral JM216, ZD0473, BBR3464 and SPI-77, which is a pegylated liposomal formulation of cisplatin, are still under investigation [10-13], whereas nedaplatin has been approved in Japan for the treatment of non-small cell lung cancer and other solid tumours. This review focuses on cisplatin, carboplatin and oxaliplatin.

  18. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    Science.gov (United States)

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics

    NARCIS (Netherlands)

    Hato, S.V.; Khong, A.; Vries, I.J.M. de; Lesterhuis, W.J.

    2014-01-01

    The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent

  20. Recent Advances in Platinum (IV) Complex-Based Delivery Systems to Improve Platinum (II) Anticancer Therapy.

    Science.gov (United States)

    Han, Xiaopeng; Sun, Jin; Wang, Yongjun; He, Zhonggui

    2015-11-01

    Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy. © 2015 Wiley Periodicals, Inc.

  1. Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

    Science.gov (United States)

    Liu, Dage; Nakashima, Nariyasu; Nakano, Jun; Tarumi, Shintaro; Matsuura, Natsumi; Nakano, Takayuki; Nii, Kazuhito; Tokunaga, Yoshimasa; Go, Tetsuhiko; Yokomise, Hiroyasu

    2017-05-01

    Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0

  2. GSTP1 Ile105Val(A/G)多态性与进展期胃癌铂类药物化疗敏感性的Meta分析%Association between Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in advanced gastric cancer: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    邓成辉; 关泉林; 姜雷; 李小奇; 甘亮亮; 魏孔孔

    2014-01-01

    目的 定量评价进展期胃癌患者中谷胱甘肽S转移酶pi(GSTP1)基因105氨基酸位点Ile/Val多态性与铂类药物化疗敏感性的关系.方法 检索中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)、中国生物医学文献数据库(CBM)、万方数据库、PubMed、EMBASE、Cochrane Library,收集国内外公开发表的关于GSTP1 Ilel05Val基因多态性与胃癌铂类药物化疗敏感性关系的文献.临床有效(完全缓解+部分缓解)作为评价化疗敏感性的指标.运用RevMan 5.2进行Meta分析,计算合并比值比(OR)及95%可信区间(CI),运用Stata 12.0识别是否存在发表偏倚.结果 本研究纳入6项研究共计病例724例,Meta分析结果显示,各基因型间(GG+GAvs AA:OR=2.38,95% CI为1.29~4.38;GG vs GA+ AA:OR=3.66,95% CI为1.18 ~ 11.39;GG vs AA:OR=4.42,95% CI为1.28~15.26)以及亚洲人群亚组(GG+ GA vs AA:OR=2.93,95%CI为1.33 ~ 6.48)中GSTP1 Ilel05Val多态性与化疗敏感性的差异有统计学意义.结论 GSTP1 Ile105VaI(A/G)基因多态性可能与进展期胃癌铂类化疗药物敏感性相关.%Objective To quantitatively evaluate the association between Ile105Val polymorphism of glutathione S-transferase pi (GSTP1) and sensitivity to platinum-based chemotherapy in advanced gastric cancer.Methods The relevant published literatures about Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in gastric cancer were retrieved from China National Knowledge Internet (CNKI),VIP,Chinese Biomedical Literature Data (CBM),Wan-Fang databases,PubMed,EMBASE and Cochrane Library.Clinical response (complete response and partial response) was employed to estimate chemosensitivity.Meta-analysis was conducted by the RevMan 5.2 software,odds ratio (OR) with 95% confidence interval (CI) were calculated.Publication bias was identified using Stata 12.0 software.Results A total of 724 cases from 6 case-control trials were included.The results of

  3. Hope, quality of life, and benefit from treatment in women having chemotherapy for platinum-resistant/refractory recurrent ovarian cancer: the gynecologic cancer intergroup symptom benefit study.

    Science.gov (United States)

    Sjoquist, Katrin M; Friedlander, Michael L; O'Connell, Rachel L; Voysey, Merryn; King, Madeleine T; Stockler, Martin R; Oza, Amit M; Gillies, Kim; Martyn, Julie K; Butow, Phyllis N

    2013-01-01

    Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the hope of benefit. We sought to determine the relationships between: (a) trait hope, expectation of symptom benefit from chemotherapy, and anxiety and depression; (b) hope and perceived efficacy of chemotherapy; and (c) unfulfilled hope (where expectations for benefit are not fulfilled) and depression. Methods. Adult patients enrolled within stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study were included. Patient. Reported outcomes were collected from 126 women with predominantly platinum-resistant ovarian cancer at baseline, prior to the first four treatment cycles (12-16 weeks), and four weeks after completing chemotherapy or at disease progression, whichever came first. Associations were assessed with Spearman rank correlation coefficient (r) and odds ratio. Results. Trait hope and expectation of symptom benefit from chemotherapy were weakly correlated with each other (r = 0.25). Trait hope, but not expectation of symptom benefit, was negatively correlated with anxiety (r = -0.43) and depression (r = -0.50). The smaller the discrepancy between perceived and expected symptom benefit, the less likely the patient was to have scores indicative of depression (odds ratio: 0.68; 95% confidence interval: 0.49-0.96; p = .026). Conclusion. Trait hope and expectation of symptom benefit from chemotherapy appear to be distinct and independent of the aspects of quality of life and scores for depression. Hope did not appear to affect perceived efficacy of chemotherapy in alleviating symptoms, but women whose expectation of symptom benefit from chemotherapy was not fulfilled were more likely to have scores indicative of depression. It may be preferable to encourage hope toward achievable goals rather than toward benefits from chemotherapy.

  4. Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

    Science.gov (United States)

    Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

    2017-06-15

    The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m(2) on day 1), cisplatin (75 mg/m(2) on day 1), and a continuous infusion of fluorouracil (500 mg/m(2) /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Expression of Drug-Resistant Factor Genes in Hepatocellular Carcinoma Patients Undergoing Chemotherapy with Platinum Complex by Arterial Infusion

    Directory of Open Access Journals (Sweden)

    Shiro Ueda

    2010-09-01

    Full Text Available This study investigated gene expression of drug resistance factors in biopsy tissue samples from hepatocellular carcinoma (HCC patients undergoing chemotherapy by platinum complex. Liver biopsy was performed to collect tissue from the tumor site (T and the non-tumor site (NT prior to the start of treatment. For drug-resistant factors, drug excretion transporters cMOAT and MDR-1, intracellular metal binding protein MT2, DNA repair enzyme ERCC-l and inter-nucleic cell transport protein MVP, were investigated. The comparison of the expression between T and NT indicated a significant decrease of MT2 and MDR-1 in T while a significant increase in ERCC-1 was noted in T. Further, expression was compared between the response cases and non-response cases using the ratios of expression in T to those in NT. The response rate was significantly low in the high expression group when the cutoff value of cMOAT and MT2 was set at 1.5 and 1.0, respectively. Furthermore, when the patients were classified into A group (cMOAT ≧ 1.5 or MT2 ≧ 1.0 and B group (cMOAT < 1.5 and MT2 < 1.0, the response rate of A group was significantly lower than B group when we combined the cutoff values of cMOAT and MT2. It is considered possible to estimate the therapeutic effect of platinum complex at a high probability by combining the expression condition of these two genes.

  6. Chemotherapy of glioblastoma by targeted liposomal platinum compounds with focused ultrasound.

    Science.gov (United States)

    Yang, Feng-Yi; Horng, Shih-Cheng

    2013-01-01

    Giloblastoma multiforme (GBM) is the most aggressive brain neoplasm, and patients have a poor prognosis after radiation and chemotherapy. The chemotherapy protocols still marginally improve the anti-tumor effect of patients with glioblastoma because the therapeutic dosage of many drugs is impeded by the blood-brain barrier (BBB). The use of liposomal drugs to GBM treatment might benefit from a more crossing of the BBB due to the lipid nature achieving higher doses of drug at the tumor sites. Human GBM-bearing mice were injected intravenously with cisplatin encapsulated in atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes or unconjugated liposome. Moreover, the administration of AP-1 liposomal cisplatin (lipoplatin) followed by focused ultrasound (FUS)-induced BBB disruption. Tumor progression was monitored by biophotonic imaging. The preliminary data demonstrated that the GBM chemotherapy with AP-1 lipoplatin followed by pulsed FUS showed a modest improvement of tumor growth in the brain compared to the group treated with lipoplatin alone. Further investigations are needed to use this new targeted lipoplatin in treatment of malignancies.

  7. Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

    Directory of Open Access Journals (Sweden)

    Alexander S Baras

    Full Text Available The 5-year cancer specific survival (CSS for patients with muscle invasive urothelial carcinoma of the bladder (MIBC treated with cystectomy alone is approximately 50%. Platinum based neoadjuvant chemotherapy (NAC plus cystectomy results in a marginal 5-10% increase in 5-year CSS in MIBC. Interestingly, responders to NAC (based biomarkers detectable by immunohistochemistry (IHC. These candidate biomarkers were subsequently tested in tissue microarrays derived from an independent cohort of NAC naive MIBC biopsy specimens from whom the patients were treated with neoadjuvant gemcitabine cisplatin NAC and subsequent cystectomy. The clinical parameters that have been previously associated with NAC response were also examined in our cohort.Our analyses of the available mRNA gene expression data in a discovery cohort (n = 33 and the HPA resulted in 8 candidate protein biomarkers. The combination of GDPD3 and SPRED1 resulted in a multivariate classification tree that was significantly associated with NAC response status (Goodman-Kruskal γ = 0.85 p<0.0001 in our independent NAC treated MIBC cohort. This model was independent of the clinical factors of age and clinical tumor stage, which have been previously associated with NAC response by our group. The combination

  8. A pilot study of first-line chemotherapy with 5-FU and Platinum in advanced and recurrent cancer of the cervix

    Directory of Open Access Journals (Sweden)

    Ghaemmaghami F

    2003-06-01

    Full Text Available This study was designed to assess the role of first-line chemotherapy with 5-FU and platinum in the treatment of advanced or recurrent cervical cancer, ten patients with advanced or recurrent cancer of the cervix, with no prior chemotherapy were entered in phase II trial, from Oct. 2000 to Nov. 2001. Eight patients were treated with cis-platinum (50 mg/m2 over 60 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days and two patients with impaired renal function were treated with carboplatin (300 mg/m2 over 15 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days every three weeks, until progression of disease or prohibitive toxicity had been observed. Median age was 52 years (range: 28-70 years. Ten patients received a total of 42 cycles of chemotherapy. The mean number of chemotherapy cycles was 4.2 (median 4, range: 3-7. Three patients had partial response (30%, CI, 1.7%-58.5%. Mean response duration was 198 days (range: 122-273 days. Four patients required red blood cell transfusions; three of them had grade II and one of them grade III nausea and vomiting Two had fever and neutropenia (one developed acute renal insufficiency, and there wee no treatment related mortalities. First-line chemotherapy with platinum and 5-FU for advanced recurrent cervical cancer is promising and deserves consideration for large phase III trials.

  9. Flow Injection Analysis with Electrochemical Detection for Rapid Identification of Platinum-Based Cytostatics and Platinum Chlorides in Water

    Directory of Open Access Journals (Sweden)

    Marketa Kominkova

    2014-02-01

    Full Text Available Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED. Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer and potential changes (1,000, 1,100 and 1,200 mV offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

  10. Flow injection analysis with electrochemical detection for rapid identification of platinum-based cytostatics and platinum chlorides in water.

    Science.gov (United States)

    Kominkova, Marketa; Heger, Zbynek; Zitka, Ondrej; Kynicky, Jindrich; Pohanka, Miroslav; Beklova, Miroslava; Adam, Vojtech; Kizek, Rene

    2014-02-04

    Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED). Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer) and potential changes (1,000, 1,100 and 1,200 mV) offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

  11. Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

    LENUS (Irish Health Repository)

    Gallagher, D J

    2013-09-01

    Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity.

  12. First platinum moderated positron beam based on neutron capture

    CERN Document Server

    Hugenschmidt, C; Repper, R; Schreckenbach, K; Sperr, P; Triftshaeuser, W

    2002-01-01

    A positron beam based on absorption of high energy prompt gamma-rays from thermal neutron capture in sup 1 sup 1 sup 3 Cd was installed at a neutron guide of the high flux reactor at the ILL in Grenoble. Measurements were performed for various source geometries, dependent on converter mass, moderator surface and extraction voltages. The results lead to an optimised design of the in-pile positron source which will be implemented at the Munich research reactor FRM-II. The positron source consists of platinum foils acting as gamma-e sup + e sup - -converter and positron moderator. Due to the negative positron work function moderation in heated platinum leads to emission of monoenergetic positrons. The positron work function of polycrystalline platinum was determined to 1.95(5) eV. After acceleration to several keV by four electrical lenses the beam was magnetically guided in a solenoid field of 7.5 mT leading to a NaI-detector in order to detect the 511 keV gamma-radiation of the annihilating positrons. The posi...

  13. The impact of novel retinoids in combination with platinum chemotherapy on ovarian cancer stem cells.

    Science.gov (United States)

    Whitworth, Jenny M; Londoño-Joshi, Angelina I; Sellers, Jeffrey C; Oliver, Patsy J; Muccio, Donald D; Atigadda, Venkatram R; Straughn, J Michael; Buchsbaum, Donald J

    2012-04-01

    Retinoids are important modulators of cell growth, differentiation, and proliferation. 9cUAB30, 9cUAB124, and 9cUAB130 are three novel retinoid compounds that show cytotoxic effects in other malignancies. We evaluated these novel retinoids in combination with chemotherapy against ovarian cancer stem cells (CSCs) in vitro and in an ex vivo model. A2780 cells were plated in 96-well plates and treated with retinoid, carboplatin, or combination therapy. Cell viability was evaluated using ATPLite assay. The A2780 cell line was also analyzed for CSCs by evaluating ALDH activity using flow cytometry. A2780 cells treated ex vivo with retinoids and chemotherapy were injected into the flank of athymic nude mice in order to evaluate subsequent tumor initiating capacity. A2780 cells were sensitive to treatment with retinoids and carboplatin. The best treatment resulted from the combination of retinoid 9cUAB130 and carboplatin. Untreated A2780 cells demonstrated ALDH activity in 3.3% of the cell population. Carboplatin treatment enriched ALDH activity to 27.3%, while 9cUAB130±carboplatin maintained the ALDH positive levels similar to untreated controls (2.3% and 6.7%, respectively). Similar results were found in tumorsphere-forming conditions. Flank injections of ex vivo treated A2780 cells resulted in 4/4 mice developing tumors at 40 days in the untreated group, while 0/4 tumors developed in the 9cUAB130 and carboplatin treated group. Combination treatment with carboplatin and retinoids reduced cell-viability, reduced CSC marker expression, and inhibited tumorigenicity, making it a more effective treatment when compared with carboplatin alone. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. [Docetaxel (TXT) and irinotecan (CPT-11) as a second-line chemotherapy for platinum-pretreated squamous cell carcinoma of the head and neck].

    Science.gov (United States)

    Sakoda, Takema; Morizane, Rie; Nosaka, Aya; Nakahara, Kei; Fukutsuji, Kenji; Yamanishi, Mie; Ikeda, Hiroki; Shibano, Akira; Enomoto, Tadao; Kitano, Hiroya

    2008-08-01

    Cisplatin(CDDP), combined with 5-fluorouracil, is considered one of the most active chemotherapeutic combinations in the treatment of patients with squamous cell carcinoma of the head and neck(SCCHN)and is accepted today as a standard regimen. But second-line chemotherapy for platinum-pretreated patients has not yet been established. Eighteen patients with recurrent SCCHN were treated using docetaxel (TXT) and irinotecan (CPT-11). All of them had been pretreated with platinum included regimen. In principle, our regimen consisted of TXT(50-60 mg/m(2), day 1) and CPT-11(60-90 mg/m(2), day 1, 8, 15). The adverse events were significant, including 13(72.2%)of grade 3 and 4 neutropenia, but acceptable. Seventeen patients were eligible for evaluation of response. Two complete responses (CR; 11.8%)and 6 partial responses (PR; 35.3%)were observed with an overall response rate of 47.1%. Patients pretreated with TXT had a 25.0% response rate (1 PR and 3 progressive disease). We conclude that the combination of TXT and CPT-11 is a worthwhile treatment for platinum-pretreated SCCHN as a 2nd-line-chemotherapy.

  15. Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Du, Gangjun; Yang, Yiming; Yang, Yingming; Zhang, Yaping; Sun, Ting; Liu, Weijie; Wang, Yingying; Li, Jiahuan; Zhang, Houyun

    2013-04-01

    Patients with advanced non-small-cell lung cancer (NSCLC) have poor survival, and platinum-based chemotherapy agents are the standard first-line chemotherapy agents for advanced NSCLC. This study aimed to identify predictive factors associated with the response to chemotherapy and survival in 258 patients with advanced NSCLC treated with platinum-based chemotherapy. Stage IIIA-IV NSCLC patients diagnosed in Kaifeng second people's hospital (Henan, China) between March 2002 and September 2011 were retrospectively reviewed. All of the patients had received platinum-based chemotherapy, and patients were followed up to date of death or last follow-up to obtain data of response to chemotherapy and survival. Potential prognostic factors such as gender, age, tumor size, tumor type, histologic stage, anemia, calcium levels, ECOG performance status (PS), thrombocytosis, TTF-1, p63, and connexin 43 were analyzed. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method and Cox regression model. A univariate analysis indicated that thrombocytosis and connexin 43 were found to be significant prognostic factors (p thrombocytosis was associated with increased mortality and resistance to chemotherapy in chemotherapy responders. In addition, all 21 patients of the 5-year OS were from chemotherapy responders with connexin 43 ≥ +2 or non-thrombocytosis. Thrombocytosis and connexin 43 absence may be reliable surrogate markers for the prediction of chemotherapy response and prognosis for patients with advanced NSCLC, and assessment of these factors may identify a population of patients with advanced NSCLC that is likely to have a prolonged life expectancy.

  16. Elaboration and Properties of Nanocomposite Structures Based on Crown Modified Platinum Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    H.Perez; S.Cavaliere-jaricot; P-A.Albouy; A.Etcheberry

    2007-01-01

    1 Results This paper presents the development of platinum nanocomposites structures based on organically modified c.a.2 nm core platinum nanoparticles.The chemical modification of the 4-mercaptoaniline functionalized particles by various in coming molecules is evidenced and precisely quantified.The particles can be dissolved like molecules in various solvents depending on the features of the new crown and X-rays shows that the interparticle distance is affected by the crown modification.These platinum n...

  17. Surface segregations in platinum-based alloy nanoparticles

    Science.gov (United States)

    Yamakawa, Shunsuke; Asahi, Ryoji; Koyama, Toshiyuki

    2014-04-01

    A phase-field model that describes the radial distributions of the ordered-disordered phase and surface segregation in a single-alloy nanoparticle is introduced to clarify the overall behavior of surface segregation of various Pt-based alloy nanoparticles. One of the obstacles to apply a platinum-transition metal alloy as a cathode electro-catalyst of a polymer electrolyte fuel cell is the need to ensure the retention of the designed surface composition in an alloy nanoparticle against the alloy combinations, a particle size, and heat treatment. From the results of calculations for CrPt, FePt, CoPt, NiPt, CuPt, PdPt, IrPt, and AuPt binary nanoparticles with diameters below 10 nm at 973.15 K, the compositional variation within a single particle was found to depend on the balance between the atomic interaction within particles and the surface free energy. In addition, the obtained specific steady-state composition of the surface varied significantly with alloy combination and particle diameter. Based on the general tendencies of a binary system to exhibit segregation, attempts to control the amount of platinum segregation on the surface using a ternary-alloy system were examined.

  18. Second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Song ZB

    2014-10-01

    Full Text Available Zhengbo Song, Yiping Zhang Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Purpose: This retrospective analysis evaluates the clinical efficacy and toxicity of second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma (ESCC. Methods: We retrospectively reviewed patients who had received second-line docetaxel-based chemotherapy for advanced ESCC in Zhejiang Cancer Hospital between January 2008 and December 2011. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis. Results: Eighty-five patients received docetaxel-based second-line chemotherapy after the failure of first-line fluorouracil-based treatment. Forty-four patients received docetaxel-platinum chemotherapy, and 41 received docetaxel single-agent treatment. The progression-free survival (PFS and overall survival (OS were 3.5 and 5.5 months in all of the patients, respectively. There were no statistically significant differences in PFS and OS between docetaxel-platinum and docetaxel single-agent chemotherapy groups (P-value 0.38 and 0.64, respectively. Response to first-line chemotherapy was a favorable prognostic factor for PFS in uni- and multivariate analyses (P-value 0.005 and 0.028, respectively. Conclusion: Patients with docetaxel-based second-line treatment obtained a moderate PFS advantage in advanced ESCC. Response to first-line chemotherapy was a favorable prognostic factor for PFS of second-line chemotherapy in advanced ESCC. Keywords: ESCC, efficacy, toxicity

  19. Structure of matrix metalloproteinase-3 with a platinum-based inhibitor.

    Science.gov (United States)

    Belviso, Benny Danilo; Caliandro, Rocco; Siliqi, Dritan; Calderone, Vito; Arnesano, Fabio; Natile, Giovanni

    2013-06-18

    An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).

  20. The interaction of platinum-based drugs with native biologically relevant proteins

    NARCIS (Netherlands)

    Brauckmann, Christine; Wehe, Christoph A.; Kieshauer, Michael; Lanvers-Kaminsky, Claudia; Sperling, Michael; Karst, Uwe

    2013-01-01

    This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like beta-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based antica

  1. How much platinum passes the placental barrier? Analysis of platinum applications in 21 patients with cervical cancer during pregnancy.

    Science.gov (United States)

    Köhler, Christhardt; Oppelt, Peter; Favero, Giovanni; Morgenstern, Bernd; Runnebaum, Ingo; Tsunoda, Audrey; Schmittel, Alexander; Schneider, Achim; Mueller, Michael; Marnitz, Simone

    2015-08-01

    Cervical cancer is the most common solid cancer diagnosed in pregnancy. Platinum is an active drug in the treatment of patients with cervical cancer. In the second and third trimesters, platinum is used to prevent cancer progression until fetal maturity is reached. However, knowledge about the transplacental passage of platinum is very limited. Between May 2008 and June 2014, platinum-based neoadjuvant chemotherapy was applied to 21 consecutive patients with cervical cancer diagnosed in their second trimester. At the time of delivery by cesarean delivery, synchronous samples from maternal blood, umbilical cord blood, and amniotic fluid were taken and analyzed for platinum concentrations. The mean week of gestation at cancer diagnosis was 17 (13-23). On average 3 (range, 2-4) cycles of chemotherapy were applied. Cesarean deliveries were carried out between 30.4 and 36.5 weeks of gestation. Twenty-two healthy babies without renal, hepatic, auditory, or hematopoietic impairment were delivered. Platinum concentrations in umbilical cord blood and amniotic fluid were 23-65% and 11-42% of the maternal blood, respectively. This series on in vivo measurement of platinum concentrations in the fetomaternal compartment observed that because of consistently lower platinum values in the fetoplacental unit, a placental filtration mechanism of platinum may be assumed. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla;

    -complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum......Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross...... the response to platinum based chemotherapy. The aim of this study was to evaluate ERCC1 expression and ERCC1 118 polymorphism in epithelial ovarian cancer and the potential association with response to platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tissue sections from 159 patients...

  3. The potential of platinum-DNA adduct determination in ex vivo treated tumor fragments for the prediction of sensitivity to cisplatin chemotherapy

    NARCIS (Netherlands)

    Welters, M.J.P.; Braakhuis, B.J.M.; Jacobs-Bergmans, A.J.; Kegel, A.; Baan, R.A.; Vijgh, W.J.F. van der; Fichtinger-Schepman, A.M.J.

    1999-01-01

    Background: Response to cisplatin-therapy is assumed to be related to the formation of platinum (Pt)-DNA adducts. Measurement of these adducts prior to therapy could be of value to improve cisplatin based cancer therapy. Materials and methods: We determined Pt-GG and Pt-AG adduct levels by use of 32

  4. Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

    Science.gov (United States)

    Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-01-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

  5. Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model.

    Science.gov (United States)

    Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-06-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

  6. Combination chemotherapy with cis-diammine-dichloro-platinum, vinblastine, and bleomycin in advanced testicular non-seminoma

    NARCIS (Netherlands)

    Stoter, G.; Sleijfer, D.Th.; Vendrik, C.P.J.; Schraffordt Koops, H.; Struyvenberg, A.; Oosterom, A.T. van; Brouwers, Th.M.; Pinedo, H.M.

    1979-01-01

    40 patients with disseminated testicular non-seminoma were treated with cis-diammine-dichloro-platinum, vinblastine, and bleomycin. Complete remission was achieved in 24 (60%) patients and partial remission in 11(28%). 22 of the 24 complete responders, who have been followed-up for a median of 11

  7. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

    Science.gov (United States)

    Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

    2016-05-21

    High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.

  8. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

    Directory of Open Access Journals (Sweden)

    Gota V

    2014-06-01

    Full Text Available Vikram Gota,1 Krunal Kavathiya,1 Kartik Doshi,1 Murari Gurjar,1 Solai E Damodaran,1 Vanita Noronha,2 Amit Joshi,2 Kumar Prabhash2 1Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, 2Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Background: Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC. While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods: Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results: Sixteen of 46 patients (35% had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively. Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively. Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion: Higher exposure to

  9. Platinum drugs and DNA repair mechanisms in lung cancer.

    Science.gov (United States)

    Bonanno, Laura; Favaretto, Adolfo; Rosell, Rafael

    2014-01-01

    The standard first-line treatment for around 80% of newly-diagnosed advanced non-small cell lung cancer (NSCLC) is chemotherapy. Currently, patients are allocated to chemotherapy on the basis of clinical conditions, comorbidities and histology. If feasible, platinum-based chemotherapy is considered as the most efficacious option. Due to the heterogeneity in terms of platinum-sensitivity among patients with NSCLC, great efforts have been made in order to identify molecular predictive markers of platinum resistance. Based on the mechanism of action of platinum, several components of DNA repair pathways have been investigated as potential predictive markers. The main DNA repair pathways involved in the repair of platinum-induced DNA damage are nucleotide excision repair and homologous recombination. The most studied potential predictive markers of platinum-sensitivity are Excision Repair Cross Complementing-1 (ERCC1) and Brest Cancer Type-I Susceptibility protein (BRCA1); however, increasing biological knowledge about DNA repair pathways suggests the potential clinical usefulness of integrated analysis of multiple DNA repair components.

  10. Platinum-induced neurotoxicity: A review of possible mechanisms.

    Science.gov (United States)

    Kanat, Ozkan; Ertas, Hulya; Caner, Burcu

    2017-08-10

    Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despite discontinuation of platinum drugs, these symptoms can persist over a long period of time. Cisplatin and oxaliplatin, among all platinum drugs, have significant neurotoxic potential. A distal dose-dependent symmetrical sensory neuropathy is the most common presentation of platinum neurotoxicity. DNA damage-induced apoptosis of dorsal root ganglion (DRG) neurons seems to be the principal cause of neurological symptoms. However, DRG injury alone cannot explain some unique symptoms such as cold-aggravated burning pain affecting distal extremities that is observed with oxaliplatin administration. In this article, we briefly reviewed potential mechanisms for the development of platinum drugs-associated neurological manifestations.

  11. Under-Reported Aspects of Platinum Drug Pharmacology

    Directory of Open Access Journals (Sweden)

    Dirk Theile

    2017-02-01

    Full Text Available Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation reaction kinetics that determine site-specific toxicity; second, the impact on RNA molecules. Knowledge of the ‘RNA world’ has dramatically changed our understanding of cellular and molecular biology. The inherent RNA-crosslinking properties should make platinum-based drugs interact with coding and non-coding RNAs. Third, we will discuss the impact on the immune system, which is now recognized to substantially contribute to chemotherapy efficacy. Together, platinum drugs are in fact old drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave the way to new drugs or an improved application of the already existing compounds.

  12. Tissue Platinum Concentration and Tumor Response in Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Kim, Eric S.; Lee, J. Jack; He, Guangan; Chow, Chi-Wan; Fujimoto, Junya; Kalhor, Neda; Swisher, Stephen G.; Wistuba, Ignacio I.; Stewart, David J.; Siddik, Zahid H.

    2012-01-01

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. Tissue platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue platinum concentration correlated significantly with percent reduction in tumor size (P < .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on platinum concentration. Patients with higher platinum concentration had longer time to recurrence (P = .034), progression-free survival (P = .018), and overall survival (P = .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue platinum concentration and response in NSCLC. It suggests that reduced platinum accumulation might be an important mechanism of platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular platinum concentration are warranted. PMID:22891266

  13. Porous platinum-based catalysts for oxygen reduction

    Science.gov (United States)

    Erlebacher, Jonah D; Snyder, Joshua D

    2014-11-25

    A porous metal that comprises platinum and has a specific surface area that is greater than 5 m.sup.2/g and less than 75 m.sup.2/g. A fuel cell includes a first electrode, a second electrode spaced apart from the first electrode, and an electrolyte arranged between the first and the second electrodes. At least one of the first and second electrodes is coated with a porous metal catalyst for oxygen reduction, and the porous metal catalyst comprises platinum and has a specific surface area that is greater than 5 m.sup.2/g and less than 75 m.sup.2/g. A method of producing a porous metal according to an embodiment of the current invention includes producing an alloy consisting essentially of platinum and nickel according to the formula Pt.sub.xNi.sub.1-x, where x is at least 0.01 and less than 0.3; and dealloying the alloy in a substantially pH neutral solution to reduce an amount of nickel in the alloy to produce the porous metal.

  14. 78 FR 60270 - Platinum Energy, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Science.gov (United States)

    2013-10-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Platinum Energy, LLC; Supplemental Notice That Initial Market- Based Rate...-referenced proceeding, of Platinum Energy, LLC's application for market-based rate authority, with...

  15. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

    OpenAIRE

    Serpe L; Gallicchio M; Canaparo R; Dosio F

    2014-01-01

    Loredana Serpe, Margherita Gallicchio, Roberto Canaparo, Franco DosioDepartment of Drug Science and Technology, University of Turin, ItalyAbstract: Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovar...

  16. Efficient light-emitting devices based on platinum-complexes-anchored polyhedral oligomeric silsesquioxane materials

    KAUST Repository

    Yang, Xiaohui

    2010-08-24

    The synthesis, photophysical, and electrochemical characterization of macromolecules, consisting of an emissive platinum complex and carbazole moieties covalently attached to a polyhedral oligomeric silsesquioxane (POSS) core, is reported. Organic light-emitting devices based on these POSS materials exhibit a peak external quantum efficiency of ca. 8%, which is significantly higher than that of the analogous devices with a physical blend of the platinum complexes and a polymer matrix, and they represent noticeable improvement in the device efficiency of solution-processable phosphorescent excimer devices. Furthermore, the ratio of monomer and excimer/aggregate electroluminescent emission intensity, as well as the device efficiency, increases as the platinum complex moiety presence on the POSS macromolecules decreases. © 2010 American Chemical Society.

  17. An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based chemotherapeutic drugs.

    Science.gov (United States)

    Sheridan, C; Brumatti, G; Elgendy, M; Brunet, M; Martin, S J

    2010-12-09

    Cisplatin is a widely used cancer chemotherapeutic that promotes DNA damage-associated apoptosis. Although platinum compounds are known to form DNA adducts and provoke DNA damage, the molecular mechanism of cisplatin-induced cell death remains unclear. In this article, we show that the BH3-only protein Noxa is strongly transcriptionally upregulated in response to cisplatin and related platinum compounds. Cisplatin-induced Noxa expression was ERK dependent, but p53 independent, and inhibition of ERK activation markedly attenuated cisplatin-induced cell death, as well as Noxa expression. Furthermore, siRNA-mediated ablation of Noxa expression also inhibited cisplatin-induced cell death and permitted clonogenic survival. These observations reveal a novel ERK-regulated route to Noxa expression that is important for the cell killing activity of platinum-based chemotherapeutic drugs.

  18. Application of liposomal technologies for delivery of platinum analogs in oncology

    Directory of Open Access Journals (Sweden)

    Liu D

    2013-08-01

    Full Text Available Demin Liu1, Chunbai He1, Andrew Z Wang2, Wenbin Lin1 1Department of Chemistry, University of Chicago, Chicago, IL, USA; 2Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™, SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research. Keywords: liposome, platinum analog, drug delivery, cancer

  19. Novel compliant electrodes based on platinum salt reduction

    Science.gov (United States)

    Delille, Remi; Urdaneta, Mario; Hsieh, Kuangwen; Smela, Elisabeth

    2006-03-01

    A compliant electrode material is presented that was inspired by the electroding process used to manufacture ionic polymer-metal composites (IPMCs). However, instead of an ion-exchange membrane, a UV-curable acrylated urethane elastomer is employed. The electrode material consists of the UV-curable elastomer (Loctite 3108) loaded with tetraammineplatinum(II) chloride salt particles through physical mixing and homogenization. The composite material is made conductive by immersion in a reducing agent, sodium borohydride, which reduces the salt to platinum metal on the surface of the elastomer film. Because the noble metal is mixed into the elastomer precursor as a salt, the amount of UV light absorbed by the precursor is not significantly reduced, and the composite loses little photopatternability. As a result meso-scale electrodes of varying geometries can be formed by exposing the precursor/salt mixture through a mask. The materials are mechanically and electrically characterized. The percolation threshold of the composite is estimated to be 9 vol. % platinum salt, above which the compliant electrode material exhibits a maximum conductivity of 1 S/cm. The composite maintains its electrical conductivity under axial tensile strains of up to 40%.

  20. Chemotherapy

    Science.gov (United States)

    ... tumor cells. Mitotic inhibitors—These agents are usually plant-based, natural substances that interfere with the production ... drugs Infertility Seizures Weakness Balance or coordination problems Memory or cognitive problems Brain swelling Damage to internal ...

  1. The role of support and promoter on the oxidation of sulfur dioxide using platinum based catalysts

    DEFF Research Database (Denmark)

    Koutsopoulos, Sotiris; Rasmussen, Søren Birk; Eriksen, Kim Michael

    2006-01-01

    The catalytic oxidation of SO2 to SO3 was studied over platinum based catalysts in the absence and the presence of dopants. The active metal was supported on silica gel or titania (anatase) by impregnation. The activities of the silica supported catalysts were found to follow the order PtRh/SiO2...

  2. THE SEPARATION OF BASE METALS FROM PLATINUM METALS BY ION EXCHANGE

    Institute of Scientific and Technical Information of China (English)

    JIANGLingen; HUANGYan

    1992-01-01

    In this paper the separation of base metals Fe,Co,Ni and Cu from the platinum metals on a cation exchanger column was studies.The convenient separation conditions are 0.5mol·dm-3 NaCl,pH=2. The recovery efficiency of Rh is 98%.

  3. Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity.

    Science.gov (United States)

    Sengupta, Poulomi; Basu, Sudipta; Soni, Shivani; Pandey, Ambarish; Roy, Bhaskar; Oh, Michael S; Chin, Kenneth T; Paraskar, Abhimanyu S; Sarangi, Sasmit; Connor, Yamicia; Sabbisetti, Venkata S; Kopparam, Jawahar; Kulkarni, Ashish; Muto, Katherine; Amarasiriwardena, Chitra; Jayawardene, Innocent; Lupoli, Nicola; Dinulescu, Daniela M; Bonventre, Joseph V; Mashelkar, Raghunath A; Sengupta, Shiladitya

    2012-07-10

    Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC(50) values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a next-generation platinum-based agent in the clinics.

  4. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, M.; Jeppesen, Ulla

    2007-01-01

    The response of tumor cells to platinum-based chemotherapy involves DNA repair mechanisms. Excision repair cross-complementation group 1 (ercc1) is one of the leading genes involved in DNA repair, and several studies have linked ercc1 to platinum resistance in cell lines and in human cancers....... A common single nucleotide polymorphism (SNP) of ercc1 at codon 118 has been proposed to impair ercc1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum-based chemotherapy. The primary aim of the present study was to evaluate ERCC1 expression and ercc1 codon...... 118 polymorphism in epithelial ovarian cancer (EOC) and their possible predictive value in patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tissue sections from 159 patients with advanced EOC were used for immunohistochemistry. Ercc1 codon 118 SNP genotyping...

  5. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

    Full Text Available Platinum-based chemotherapy is commonly used for the treatment of locally advanced and metastatic bladder cancer. However, there are currently no methods to predict chemotherapy response in this disease setting. A better understanding of the biology of bladder cancer has led to developments of molecular biomarkers that may help guide clinical decision making. These biomarkers, while promising, have not yet been validated in prospective trials and are not ready for clinical applications. As alkylating agents, platinum drugs kill cancer cells mainly through induction of DNA damage. A microdosing approach is currently being tested to determine if chemoresistance can be identified by measuring platinum-induced DNA damage using highly sensitive accelerator mass spectrometry technology. The hope is that these emerging strategies will help pave the road towards personalized therapy in advanced bladder cancer.

  6. Application of liposomal technologies for delivery of platinum analogs in oncology.

    Science.gov (United States)

    Liu, Demin; He, Chunbai; Wang, Andrew Z; Lin, Wenbin

    2013-01-01

    Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™), SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research.

  7. Application of liposomal technologies for delivery of platinum analogs in oncology

    Science.gov (United States)

    Liu, Demin; He, Chunbai; Wang, Andrew Z; Lin, Wenbin

    2013-01-01

    Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™), SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research. PMID:24023517

  8. Self-assembled platinum nanochains based on octreotide acetate

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xiaoning; Gao, Dawei, E-mail: dwgao@ysu.edu.cn; Gao, Faming, E-mail: fmgao@ysu.edu.cn; Li, Na; Zhou, Jing [Yanshan University, Applying Chemistry Key Lab of Hebei Province (China); Hao, Jikui [Illinois Institute of Technology, Department of Chemical and Biological Engineering (United States)

    2013-09-15

    Biological scaffolds are used for the synthesis of inorganic materials due to their ability to self-assemble and nucleate crystal formation. We reported a facile method for preparing self-assembled Pt nanochains by using octreotide acetate (AOC) as bio-template in aqueous environment. The influence of solution pH was examined to define the optimal conditions for the formation of the AOC bio-templated Pt nanoparticles (PtNPs) arrays, the AOC has diameter about 55 nm at pH 2.0, for comparison, at pH 9.0, the diameter of AOC is about 25 nm. After 24-h incubation of AOC (pH 2.0) with PtCl{sub 4} and chemical reduction with borane-dimethyl-amine, uniform platinum nanoparticles (mean diameter 2.5 {+-} 0.5 nm) directed by AOC were formed. Preliminary characterizations of the synthesized PtNPs were performed using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and selected area of electron diffraction. The cytotoxicity of Pt/octreotide acetate complexes (PtNPs-AOC) and AOC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The results indicated that the antiproliferative effect of PtNPs-AOC is as high as AOC. In addition, the nano-design architecture of the Pt particles plays a crucial role in a strong enhancement of the biological efficiency of radiations, making PtNPs-AOC a promising material for anticancer drug delivery in the future.

  9. A Metaheuristic Algorithm Based on Chemotherapy Science: CSA

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Salmani

    2017-01-01

    Full Text Available Among scientific fields of study, mathematical programming has high status and its importance has led researchers to develop accurate models and effective solving approaches to addressing optimization problems. In particular, metaheuristic algorithms are approximate methods for solving optimization problems whereby good (not necessarily optimum solutions can be generated via their implementation. In this study, we propose a population-based metaheuristic algorithm according to chemotherapy method to cure cancers that mainly search the infeasible region. As in chemotherapy, Chemotherapy Science Algorithm (CSA tries to kill inappropriate solutions (cancers and bad cells of the human body; however, this would inevitably risk incidentally destroying some acceptable solutions (healthy cells. In addition, as the cycle of cancer treatment repeats over and over, the algorithm is iterated. To align chemotherapy process with the proposed algorithm, different basic terms and definitions including Infeasibility Function (IF, objective function (OF, Cell Area (CA, and Random Cells (RCs are presented in this study. In the terminology of algorithms and optimization, IF and OF are mainly applicable as criteria to compare every pair of generated solutions. Finally, we test CSA and its structure using the benchmark Traveling Salesman Problem (TSP.

  10. Robust optical oxygen sensors based on polymer-bound NIR-emitting platinum(II)-benzoporphyrins

    DEFF Research Database (Denmark)

    Hutter, L.H.; Müller, B.J.; Koren, Klaus

    2014-01-01

    Several advanced optical oxygen sensor materials are presented. They are based on bright NIR-emitting platinum(II)-benzoporphyrins covalently incorporated into a variety of polymeric matrices. The dye-polymer conjugates are prepared either via Suzuki coupling of the brominated porphyrins to the s......Several advanced optical oxygen sensor materials are presented. They are based on bright NIR-emitting platinum(II)-benzoporphyrins covalently incorporated into a variety of polymeric matrices. The dye-polymer conjugates are prepared either via Suzuki coupling of the brominated porphyrins...... dyes showed significant drift of their calibration. Additionally, we present a new synthetic method for preparation of analytically pure benzoporphyrins via simple 1-step template condensation which a promising alternative to the commonly used Lindsey method. © the Partner Organisations 2014....

  11. Expression of DNA translesion synthesis polymerase η in head and neck squamous cell cancer predicts resistance to gemcitabine and cisplatin-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Wendi Zhou

    Full Text Available PURPOSE: The development of resistance against anticancer drugs has been a persistent clinical problem for the treatment of locally advanced malignancies in the head and neck mucosal derived squamous cell carcinoma (HNSCC. Recent evidence indicates that the DNA translesion synthesis (TLS polymerase η (Pol η; hRad30a gene reduces the effectiveness of gemcitabine/cisplatin. The goal of this study is to examine the relationship between the expression level of Pol η and the observed resistance against these chemotherapeutic agents in HNSCC, which is currently unknown. METHODS: Sixty-four mucosal derived squamous cell carcinomas of head and neck (HNSCC from 1989 and 2007 at the City of Hope National Medical Center (Duarte, CA were retrospectively analyzed. Pretreatment samples were immunostained with anti-Pol η antibody and the correlation between the expression level of Pol η and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40 or gemcitabine (n=9 based chemotherapy were further examined for Pol η expression level for comparison with patient response to chemotherapy. RESULTS: The expression of Pol η was elevated in 67% of the head and neck tumor samples. Pol η expression level was significantly higher in grade 1 to grade 2 tumors (well to moderately differentiated. The overall benefit rate (complete response+ partial response in patients treated with platinum and gemcitabine based chemotherapy was 79.5%, where low Pol η level was significantly associated with high complete response rate (p=0.03, although not associated with overall survival. Furthermore, no significant correlation was observed between Pol η expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status. CONCLUSIONS: Our data suggest that Pol η expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy for HNSCC.

  12. ROLE OF TRANSPORTERS IN THE DISTRIBUTION OF PLATINUM-BASED DRUGS

    Directory of Open Access Journals (Sweden)

    Saliha eHarrach

    2015-04-01

    Full Text Available Platinum derivatives used as chemotherapeutic drugs such as cisplatin and oxaliplatin have a potent antitumor activity. However, severe side effects such as nephro-, oto-, and neurotoxicity are associated with their use. Effects and side effects of platinum-based drugs are in part caused by their transporter-mediated uptake in target and non target cells. In this mini review, the transport systems involved in cellular handling of platinum derivatives are illustrated, focusing on transporters for cisplatin. The copper transporter 1 seems to be of particular importance for cisplatin uptake in tumor cells, while the organic cation transporter (OCT 2, due to its specific organ distribution, may play a major role in the development of undesired cisplatin side effects. In polarized cells, e.g. in renal proximal tubule cells, apically expressed transporters, such as multidrug and toxin extrusion protein 1, mediate secretion of cisplatin and in this way contribute to the control of its toxic effects. Specific inhibition of cisplatin uptake transporters such as the OCTs may be an attractive therapeutic option to reduce its toxicity, without impairing its antitumor efficacy.

  13. DFT-based QSAR and QSPR models of several cis-platinum complexes: solvent effect.

    Science.gov (United States)

    Sarmah, Pubalee; Deka, Ramesh C

    2009-06-01

    Cytotoxic activities of cis-platinum complexes against parental and resistant ovarian cancer cell lines were investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) based descriptors. The calculated parameters were found to increase the predictability of each QSAR model with incorporation of solvent effects indicating its importance in studying biological activity. Given the importance of logarithmic n-octanol/water partition coefficient (log P(o/w)) in drug metabolism and cellular uptake, we modeled the log P(o/w) of 24 platinum complexes with different leaving and carrier ligands by the quantitative structure-property relationship (QSPR) analysis against five different concentrations of MeOH using DFT and molecular mechanics derived descriptors. The log P(o/w) values of an additional set of 20 platinum complexes were also modeled with the same descriptors. We investigated the predictability of the model by calculating log P(o/w) of four compounds in the test set and found their predicted values to be in good agreement with the experimental values. The QSPR analyses performed on 24 complexes, combining the training and test sets, also provided significant values for the statistical parameters. The solvent medium played an important role in QSPR analysis by increasing the internal predictive ability of the models.

  14. Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence.

    Science.gov (United States)

    Vezzu, Dileep A K; Lu, Qun; Chen, Yan-Hua; Huo, Shouquan

    2014-05-01

    A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the N^C^N-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the C^N^N-coordinated platinum complex based on 6-phenyl-2,2'-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by N^C^N- and C^N^N-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the N^C^N-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed that the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis were studied by western blot analysis and the activation of PARP via caspase 7 was observed.

  15. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas.

    Science.gov (United States)

    Douglas, James G; Rockhill, Jason K; Olson, James M; Ellenbogen, Richard G; Geyer, J Russell

    2006-01-01

    The objective of this study was to evaluate retrospectively one institution's experience treating pediatric central nervous system (CNS) pure germinomas with platinum-based chemotherapy followed by focal, reduced-dose irradiation. Eight patients were identified with localized, pure CNS germinomas from 1993 to 2004 at the authors' institution. The median age at diagnosis was 13 years (range 7-19). The median follow-up was 40 months (range 8-141). The tumor location was suprasellar in four, the pineal region in three, and the third ventricle in one. Irradiation was started a median of 20 weeks (range 17-22) from diagnosis and consisted of conformal fields to the primary site as determined by the initial diagnostic MR plus a 1.5- to 2-cm margin. Six of the eight patients received a dose of 3,060 cGy; two patients received 3,600 cGy. The 5-year actuarial event free survival was 71% (56-86%, 95% CI). Two patients suffered marginal (at field edge) failures and both were salvaged using reinduction platinum-based chemotherapy followed by cranial spinal irradiation and a boost to the primary tumor. The 5-year actuarial overall survival was 100%. There were no spinal failures. These data suggest that a reduction in both volume and dose (30.6-36 Gy) retains the excellent survival rates for patients with localized, pure germinomas of the CNS. A higher rate of ventricular relapse rate is observed, although salvage of those patients is feasible.

  16. Accelerated split-course radiotherapy and concomitant cis-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement in unresectable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, T.G.; Wustrow, T.P.U.; Hartenstein, R.C.; Trott, K.R.

    1988-01-01

    In patients suffering from locally advanced, unresectable squamous cell carcinoma (SCC) of the base of the tongue, the floor of the mouth, the mobile part of the tongue, the tonsils, the hypopharynx and the larynx radiotherapy yields poor results, due to local failure rather than to distant metastases. Since toxicity of radiotherapy and cytotoxic chemotherapy do not overlap entirely efforts were made to achieve better results combining these two treatment modalities. Clinical trials on simultaneous radiotherapy/chemotherapy focussed on two cytotoxic agents: Cis-dichlorodiammineplatinum(II) (cis-DDP) and 5-flourouracil (5-FU). Another approach to overcome the radioresistance of large SCC adopts accelerated fractionation. The potential tumor doubling time of sqamous cell carcinomas is about four days, and thus repopulation of surviving clonogenic tumor cells during fractionated radiotherapy may be the cause of poor treatment results. In this pilot study a twice daily fractionated split-course radiotherapy is combined with simultaneous administration of cis-DDP and 5-FU with folinic acid (FA) enhancement.

  17. A dual-emissive ionic liquid based on an anionic platinum(II) complex

    OpenAIRE

    Ogawa, Tomohiro; Yoshida, Masaki; Ohara, Hiroki; Kobayashia, Atsushi; Kato, Masako

    2015-01-01

    An ionic liquid fabricated froman anionic cyclometalated platinum(II) complex and an imidazolium cation exhibits dual emission from the monomeric and aggregated forms of the platinum complex anions, leading to temperature-dependent color changes of luminescence.

  18. A dual-emissive ionic liquid based on an anionic platinum(ii) complex.

    Science.gov (United States)

    Ogawa, Tomohiro; Yoshida, Masaki; Ohara, Hiroki; Kobayashi, Atsushi; Kato, Masako

    2015-09-07

    An ionic liquid fabricated from an anionic cyclometalated platinum(ii) complex and an imidazolium cation exhibits dual emission from the monomeric and aggregated forms of the platinum complex anions, leading to temperature-dependent color changes of luminescence.

  19. 紫杉醇脂质体与紫杉醇联合铂类同步放化疗治疗宫颈癌的随机对照研究%A randomized controlled trial of two chemotherapy regimens - paclitaxel liposome combined with platinum and paclitaxel combined with platinum in concurrent chemoradiotherapy for cervical carcinoma

    Institute of Scientific and Technical Information of China (English)

    Siyuan Zeng; Ling Li; Meiling Zhong; Wei Jiang; Yun Xiao

    2012-01-01

    Objective: The aim of the study was to compare the efficacy, side effect and influence on the survival rate of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, in concurrent chemoradiotherapy for cervical carcinoma. Methods: The 162 cases with primary cervical carcinoma diagnosed between January 2008 and November 2009 in Jiangxi Maternal and Child Health Hospital (China) were enrolled in this randomized controlled trial. Seventy-one cases were included in paclitaxel group and 91 in paclitaxel liposome group. And the chemotherapy doses were as follows: paclitaxel liposome and paclitaxel 135 mg/m2; cisplatin 80 mg/m2 or carboplatin AUC 4-6; then repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. Efficacy was evaluated according to the tumor regression six months later and follow-up was done consistently. Results: The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89 % respectively (P > 0.05). The one year cumulative survival was 91.4% for paclitaxel group and 89.2% for paclitaxel liposome group (P > 0.05). The incidence rates of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in paclitaxel liposome group were much lower than those in paclitaxel group (P 0.05). Conclusion: Paclitaxel liposome plus platinum is a safe and effective method for staging IIa-IV cervical carcinomas. While the long-term efficacy should be further observed.

  20. Mobile Phone Based System Opportunities to Home-based Managing of Chemotherapy Side Effects

    Science.gov (United States)

    Davoodi, Somayeh; Mohammadzadeh, Zeinab; Safdari, Reza

    2016-01-01

    Objective: Applying mobile base systems in cancer care especially in chemotherapy management have remarkable growing in recent decades. Because chemotherapy side effects have significant influences on patient’s lives, therefore it is necessary to take ways to control them. This research has studied some experiences of using mobile phone based systems to home-based monitor of chemotherapy side effects in cancer. Methods: In this literature review study, search was conducted with keywords like cancer, chemotherapy, mobile phone, information technology, side effects and self managing, in Science Direct, Google Scholar and Pub Med databases since 2005. Results: Today, because of the growing trend of the cancer, we need methods and innovations such as information technology to manage and control it. Mobile phone based systems are the solutions that help to provide quick access to monitor chemotherapy side effects for cancer patients at home. Investigated studies demonstrate that using of mobile phones in chemotherapy management have positive results and led to patients and clinicians satisfactions. Conclusion: This study shows that the mobile phone system for home-based monitoring chemotherapy side effects works well. In result, knowledge of cancer self-management and the rate of patient’s effective participation in care process improved. PMID:27482134

  1. Recent Approaches to Platinum(IV) Prodrugs: A Variety of Strategies for Enhanced Delivery and Efficacy.

    Science.gov (United States)

    Najjar, Anas; Rajabi, Naeema; Karaman, Rafik

    2017-01-01

    Intensive efforts have been implemented to improve the efficacy of platinum complexes especially with emerging cisplatin resistance and elevated cancer deaths. Platinum(IV) agents show better pharmacokinetics and decreased side effects compared to Platinum(II) agents. This review aims to summarize and categorize the strategies being employed to improve the efficacy of Platinum-based anticancer agents in recent years. Nanoparticles and nanoplatforms offer a vast variety of strategies in targeting specific tumor types and delivering one or two lethal drugs simultaneously. Theranostic agents are being developed to achieve enhanced imaging and provide further insight into the activity of platinum containing chemotherapy. Moreover, photoactivation of Pt(IV) prodrugs specifically at the tumor site is gaining attention due to a controlled activity. A platinum agent formulated as large multi-activity complex is the most common strategy being employed. Platinum(IV) agents offer great potential in targeting, increasing efficacy, and decreasing toxicity of Platinum-based anticancer agents. The strategies being employed are aiming to increase specificity and targeting as well as provide more potent agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. A pan-cancer analysis of inferred homologous recombination deficiency identifies potential platinum benefit in novel subtypes

    DEFF Research Database (Denmark)

    Marquard, Andrea Marion; Eklund, Aron Charles; Wang, Zhigang C.

    2014-01-01

    with platinum-based DNA-damaging agents. Reliable biomarkers to identify HR-deficient cancers prior to the initial treatment may be used to stratify patients for platinum chemotherapy. Extensive genome damage caused by deficient HR is readily observed as high frequencies of allelic imbalance and loss...... Atlas. We found that the three scores are highly correlated with each other, suggesting they measure the effect of similar types of DNA damage. We found a strong association with overall survival only in ovarian cancer, which is consistent with frequent BRCA-related HR deficiency reported for this type...... of cancer. Next, we compared the distribution of the scores across cancer types, and found that those types ordinarily receiving platinum as standard of care have the highest median scores. Importantly, in most types not generally given platinum chemotherapy we also found small sub-populations of high...

  3. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance

    Directory of Open Access Journals (Sweden)

    Euan A. Stronach

    2011-11-01

    Full Text Available Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinumresistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK, and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Re-sensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage–mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors.

  4. Biomineralization of platinum by microorganisms

    Science.gov (United States)

    Pavlova, L. M.; Radomskaya, V. I.; Shumilova, L. P.; Ionov, A. M.; Sorokin, P.

    2017-04-01

    The mechanism of platinum biomineralization by microscopic fungi is displayed based on data of electron microscopy, infrared and X-ray photoelectronic spectroscopy. It was suggested the platinum sorption process by microscopic fungi has some stages. The initial interaction is carried out by the mechanisms of physical and chemical sorption. Hereafter the reduction process of adsorbed platinum ions up to zero state is performed, probably, for account of organic compounds, which are produced by fungi biomass as metabolism result, and the process terminates by nulvalent particles aggregating up to nanosize forms. Obtained data on the platinum biomineralization extends the concept concerning the character of forming platinum nanoparticles in carbonous paleobasin.

  5. Robust Platinum-Based Electrocatalysts for Fuel Cell Applications

    Science.gov (United States)

    Coleman, Eric James

    Polymer electrolyte fuel cells (PEMFCs) are energy conversion devices that exploit the energetics of the reaction between hydrogen fuel and O 2 to generate electricity with water as the only byproduct. PEMFCs have attracted substantial attention due to their high conversion efficiency, high energy density, and low carbon footprint. However, PEMFC performance is hindered by the high activation barrier and slow reaction rates at the cathode where O2 undergoes an overall 4-electron reduction to water. The most efficient oxygen reduction reaction (ORR) catalyst materials to date are Pt group metals due to their high catalytic activity and stability in a wide range of operating conditions. Before fuel cells can become economically viable, efforts must be taken to decrease Pt content while maintaining a high level of ORR activity. This work describes the design and synthesis of a Pt-Cu electrocatalyst with ORR activity exceeding that of polycrystalline Pt. Production of this novel catalyst is quite simple and begins with synthesis of a porous Cu substrate, formed by etching Al from a Cu-Al alloy. The porous Cu substrate is then coated with a Pt layer via a spontaneous electrochemical process known as galvanic replacement. The Pt layer enhances the ORR activity (as measured by a rotating ring-disk electrode (RRDE)) and acts as a barrier towards corrosion of the Cu understructure. Growth of the Pt layer can be manipulated by time, temperature, concentration of Pt precursor, and convection rate during galvanic replacement. Data from analytical and electrochemical techniques confirm multiple Pt loadings have been achieved via the galvanic replacement process. The boost in ORR activity for the PtCu catalyst was determined to be a result of its lower affinity towards (site-blocking) OH adsorption. A unique catalyst degradation study explains the mechanism of initial catalyst ORR deactivation for both monometallic and bimetallic Pt-based catalysts. Finally, a rigorous and

  6. Role of ABC transporters in fluoropyrimidine-based chemotherapy response.

    Science.gov (United States)

    Nies, Anne T; Magdy, Tarek; Schwab, Matthias; Zanger, Ulrich M

    2015-01-01

    Since over 50 years, 5-fluorouracil (5-FU) is in use as backbone of chemotherapy treatment regimens for a wide range of cancers including colon, breast, and head and neck carcinomas. However, drug resistance and severe toxicities such as mucositis, diarrhea, neutropenia, and vomiting in up to 40% of treated patients often lead to dose limitation or treatment discontinuation. Because the oral bioavailability of 5-FU is unpredictable and highly variable, 5-FU is commonly administered intravenously. To overcome medical complications and inconvenience associated with intravenous administration, the oral prodrugs capecitabine and tegafur have been developed. Both fluoropyrimidines are metabolically converted intracellularly to 5-FU, which then needs metabolic activation to exert its damaging activity on RNA and DNA. The low response rates of 10-15% of 5-FU monotherapy can be improved by combination regimens of infusional 5-FU and leucovorin together with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI), thereby increasing response rates to 30-40%. The impact of metabolizing enzymes in the development of fluoropyrimidine toxicity and resistance has been studied in great detail. In addition, membrane drug transporters, which are critical determinants of intracellular drug concentrations, may play a role in occurrence of toxicity and development of resistance against fluoropyrimidine-based therapy as well. This review therefore summarizes current knowledge on the role of drug transporters with particular focus on ATP-binding cassette transporters in fluoropyrimidine-based chemotherapy response.

  7. Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1 and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial Carcinoma (UC Treated with First-Line Gemcitabine Plus Platinum Combination Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Miso Kim

    Full Text Available Preclinical and clinical studies have suggested that expression of ribonucleotide reductase regulatory subunit M1 (RRM1 and excision repair cross-complementation group 1 (ERCC1 is associated with resistance to gemcitabine and cisplatin, respectively. We evaluated the significance of RRM1 and ERCC1 expression to predict tumor response to gemcitabine plus platinum chemotherapy (GP and survival in advanced UC. We retrospectively collected tumor samples and reviewed clinical data of 53 patients with unresectable or metastatic UC, who were treated with first-line GP. RRM1 and ERCC1 expression were measured by immunohistochemistry. Among 53 patients, 12 (22.6% and 26 (49.1% patients had tumors that demonstrated a high expression for RRM1 and ERCC1, respectively. Twenty-nine (70.7% of 41 patients with low RRM1 expression achieved a clinical response (complete + partial responses, but only 3 (25.0% of 12 patients with high RRM1 expression achieved a clinical response after GP (P=0.007. Nineteen (70.4% of 27 patients with low ERCC1 expression achieved a clinical response, while 13 (50.0% of 26 patients with high ERCC1 expression achieved a clinical response (P=0.130. High RRM1 expression was associated with shorter progression free survival and overall survival (PFS P=0.006, OS P=0.006. Multivariate analysis confirmed that patients with high RRM1 expression had a significantly greater risk of progression and death than those with low RRM1 expression. ERCC1 status was not a significant predictor for PFS and OS. RRM1 expression was predictive and prognostic of clinical outcome in advanced UC treated with gemcitabine plus platinum combination chemotherapy.

  8. Platinum metals in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Zereini, Fathi [Frankfurt Univ. (Germany). Dept. of Environmental Analytical Chemistry; Wiseman, Clare L.S. (ed.) [Toronto Univ. (Canada). School of the Environment

    2015-03-01

    Platinum/Aluminum Oxide Model Substance; Solid State Platinum Speciation from X-ray Absorption Spectroscopic Studies of Fresh and Road Aged Three Way and Diesel Vehicle Emission Control Catalysts. 4. ENVIRONMENTAL BIOAVAILABILITY AND BIOMONITORING OF PGE: Bioavailability of Platinum Group Elements to Plants-A Review; Monitoring of Platinum Group Element Deposition by Bryophytes; Field Studies on PGE in Aquatic Ecosystems; Laboratory Studies on the Uptake and Bioaccumulation of PGE by Aquatic Plants and Animals; Biological Effects of PGE on Aquatic Organisms; Mechanisms of Uptake and Interaction of Platinum Based Drugs in Eukaryotic Cells. 5. HUMAN HEALTH EXPOSURES TO PGE AND POSSIBLE RISKS: Biomonitoring of Platinum Group Elements (PGEs) in Occupational Medicine; Platinum Metals in Airborne Particulate Matter and Their Bioaccessibility; Occupational Health Aspects of Platinum.

  9. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life...... (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. METHODS: A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL......: Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function...

  10. Palladium and platinum-palladium bi-layer based counter electrode for dye-sensitized solar cells with modified photoanode

    Science.gov (United States)

    Mokurala, Krishnaiah; Kamble, Anvita; Nemala, Siva Sankar; Bhargava, Parag; Mallick, Sudhanshu

    2015-06-01

    Dye sensitized solar cells (DSSCs) were fabricated with palladium (Pd) and platinum-palladium (Pt-Pd) bi-layer as counter electrodes, respectively. Effects of photoanode thickness and morphology on device performance were studied. DSSCs fabricated with Pd and Pd-Pt as counter electrode (CE) showed photo conversion efficiency of 4.30% and 6.20%, respectively as compared to Platinum (Pt) based CE which showed 6.65% efficiency. Lower device performance was explained with help of cyclic voltammetry and electrochemical impedance spectroscopy (EIS) measurements of the cells.

  11. Understanding platinum-induced ototoxicity.

    Science.gov (United States)

    Langer, Thorsten; am Zehnhoff-Dinnesen, Antoinette; Radtke, Susanne; Meitert, Johannes; Zolk, Oliver

    2013-08-01

    Childhood cancer survival rates are now nearly 80% in more developed European countries because of improved therapies and better supportive care. Platinum chemotherapy drugs, such as cisplatin and carboplatin, are the cornerstone of many effective therapeutic protocols for childhood cancer. However, the antitumor efficacy of cisplatin and carboplatin comes at the cost of ototoxicity, which affects at least 60% of pediatric patients. Although ototoxicity is not life threatening, it can have debilitating effects on patients' quality of life. Recently, many initiatives have been launched with the ultimate goal of reducing cisplatin and high-dose carboplatin ototoxicity without compromising antitumor efficacy. This review addresses the incidence of platinum ototoxicity and its clinical presentation, time course, and early diagnostic evaluation. Genetic and non-genetic risk factors for platinum-associated ototoxicity, and their predictive value, are discussed. Recent developments in the prevention of platinum ototoxicity are also summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    Science.gov (United States)

    Campbell, Jared M; Bateman, Emma; Peters, Micah Dj; Bowen, Joanne M; Keefe, Dorothy M; Stephenson, Matthew D

    2016-03-01

    Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.

  13. Thrombosis of abdominal aorta during cisplatin-based chemotherapy of testicular seminoma - a case report

    Directory of Open Access Journals (Sweden)

    Gehrckens Ralf

    2009-12-01

    Full Text Available Abstract Background Vascular complications occurring during cisplatin-based chemotherapy of germ cell tumours are inadequately recognized to date. Case Presentation A 49 year old man with advanced seminoma underwent two courses of chemotherapy according to the PEB regimen. Upon restaging, two thrombotic deposits were noted in the descending part of the thoracic aorta and in the infrarenal abdominal aorta, respectively. Although thrombotic plaques caused aortic occlusion of about 30%, no clinical signs of malperfusion of limbs were registered. The patient was placed on anticoagulant therapy. Six months after completion of chemotherapy, thrombotic deposits had completely resolved. In the absence of other predisposing factors, it must be assumed that cisplatin-based chemotherapy represented a strong stimulus for arterial thrombosis in the aorta. Conclusions This is the first case of endo-aortic thrombosis during chemotherapy for testicular germ cell cancer. Providers of chemotherapy must be aware of arterial thrombosis even in young patients with testicular cancer.

  14. Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘恩令; 糜若然

    2004-01-01

    Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student's t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.

  15. The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study

    Directory of Open Access Journals (Sweden)

    Fidia Mumtahana

    2014-12-01

    Full Text Available Purpose: The main purpose of this study was to analyze the effects and tolerability of Oxaliplatin-Vinorelbine combination on Platinum-resistant epithelial ovarian carcinoma (EOC patients.Methods: A single centered retrospective study comprising of 34 patients was conducted, and all 34 patients were treated with Vinorelbine 30 mg/m2 on day 1 and 8 along with Oxaliplatin 100 mg/m2 on day 1 of 3 weeks treatment cycle following progressive platinum-resistant EOC. Results: The combination showed an overall response rate (ORR of 18% (95% CI, 4.4 - 31.6 where 2 (6% patients had complete response and 4 (12% patients had partial response. Stable disease was observed in 9 (26% patients and progressive disease in 19 (56% patients. Median diseases free survival, median relapse free survival and median time to progression was 17.05 months, 4.4 months, and 1.25 months, respectively. Hematological toxicities were mild; only 1 (2.9% patient had G3 anemia and major non-hematological toxicities include nausea-vomiting, diarrhea, constipation, hepatotoxicity, fatigueness and alopecia, which are mainly limited to G1-G2 and reversible. Conclusion: The effect of this combination is moderate as a second line treatment of platinum resistant EOC; however, in comparison with other regimens of Vinorelbine and Oxaliplatin, the activity is substandard but the toxicity profile is well tolerable. Further multicenter evaluation is needed for the better understanding of the therapeutic efficacy of the combination.

  16. Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    McClung EC

    2016-03-01

    Full Text Available E Clair McClung, Robert M WenhamDepartment of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin, a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.Keywords: bevacizumab, angiogenesis, ovarian cancer, platinum-resistant ovarian cancer, recurrent ovarian cancer

  17. Inorganic nanocarriers for platinum drug delivery

    Directory of Open Access Journals (Sweden)

    Ping’an Ma

    2015-12-01

    Full Text Available Nowadays platinum drugs take up almost 50% of all the clinically used anticancer drugs. Besides cisplatin, novel platinum agents including sterically hindered platinum (II drugs, chemically reductive platinum (IV drugs, photosensitive platinum (IV drugs, and multinuclear platinum drugs have been developed recently, with a few entering clinic trials. Rapid development of nanobiotechnology makes targeted delivery of anticancer platinum agents to the tumor site possible, while simultaneously minimizing toxicity and maximizing the drug efficacy. Being versatile drug carriers to deliver platinum drugs, inorganic nanovehicles such as gold nanoparticles, iron oxide nanomaterials, carbon nanotubes, mesoporous nanosilica, metal-organic frameworks (MOFs, have been extensively studied over the past decades. In contrast to conventional polymeric and lipid nanoparticles, inorganic nanoparticles based drug carriers are peculiar as they have shown excellent theranostic effects, revealing themselves an indispensable part of future nanomedicine. Here, we will elaborate recent research advances on fabrication of inorganic nanoparticles for platinum drug delivery.

  18. Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based Chemotherapy in Testicular Cancer.

    Science.gov (United States)

    Heidegger, Isabel; Porres, Daniel; Veek, Nica; Heidenreich, Axel; Pfister, David

    2017-01-01

    Malignancies and cisplatin-based chemotherapy are both known to correlate with a high risk of venous thrombotic events (VTT). In testicular cancer, the information regarding the incidence and reason of VTT in patients undergoing cisplatin-based chemotherapy is still discussed controversially. Moreover, no risk factors for developing a VTT during cisplatin-based chemotherapy have been elucidated so far. We retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin-based chemotherapy at our institution for the development of a VTT during or after chemotherapy. Clinical and pathological parameters for identifying possible risk factors for VTT were analyzed. The Khorana risk score was used to calculate the risk of VTT. Student t test was applied for calculating the statistical significance of differences between the treatment groups. Twenty-six out of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the risk factors for developing a VTT, we found that Lugano stage ≥IIc was significantly (p = 0.0006) correlated with the risk of developing a VTT during chemotherapy. On calculating the VTT risk using the Khorana risk score model, we found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group (≥3). Patients with testicular cancer with a high tumor volume have a significant risk of developing a VTT with cisplatin-based chemotherapy. The Khorana risk score is not an accurate tool for predicting VTT in testicular cancer. © 2017 S. Karger AG, Basel.

  19. Association of long-term exposure to circulating platinum with adverse late effects in testicular cancer survivors

    NARCIS (Netherlands)

    Boer, Hink; Proost, Johannes H.; Nuver, Janine; Bunskoek, Sophie; Gietema, Joyce Q.; Geubels, Barbara M.; Altena, Renske; Zwart, Nynke; Oosting, Sjoukje; Uges, Donald R.A.; Meijer, Coby; de Vries, Elisabeth G. E.; Gietema, Jourik A.

    2012-01-01

    Background: Successful platinum(Pt)-based chemotherapy for testicular cancer (TC) comes at the price of late cardiovascular morbidity and neurotoxicity. Damage induced by circulating Pt could be an etiological mechanism. We investigated the relation between circulating Pt and late effects. Methods:

  20. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

  1. Incidence of platinum-induced ototoxicity in pediatric patients in Quebec.

    Science.gov (United States)

    Peleva, Emilia; Emami, Nader; Alzahrani, Mohammad; Bezdjian, Aren; Gurberg, Joshua; Carret, Anne-Sophie; Daniel, Sam J

    2014-11-01

    The antineoplastic agents cisplatin and carboplatin are widely-used and highly-effective against a variety of pediatric cancers. Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy. There is currently no treatment or prevention for platinum-induced ototoxicity and development of hearing loss may lead to devastating consequences on the quality of life of pediatric cancer survivors. The objective of this study is to determine the incidence of platinum-induced ototoxicity in a large series of pediatric patients and to evaluate the incidence of progression of ototoxicity after completion of treatment. A retrospective chart review of pediatric patients treated with cisplatin or carboplatin between 2000 and 2012 was conducted. The incidence of ototoxicity was determined based on the American-Speech-Language-Hearing Association (ASHA) criteria and severity was based on the Chang classification. Four hundred and sixty-six patients received platinum-based chemotherapy. Patients were excluded due to congenital hearing loss (n = 1) and insufficient data for calculating the platinum dose (n = 24) or for assessing ototoxicity (n = 135). Three hundred and six patients were included in the analysis. Post-chemotherapy ototoxicity was detected in 148 (48%) patients, and clinically-significant ototoxicity was present in 91 (30%). In addition, based on the ASHA criteria, 48% of patients (97/204) with long-term follow-up had further deterioration of their hearing after completion of treatment. Ototoxicity following chemotherapy with cisplatin or carboplatin is common and can frequently progress after the completion of treatment. Long-term follow-up is strongly recommended. © 2014 Wiley Periodicals, Inc.

  2. Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

    OpenAIRE

    Royer, B.; Kalbacher, E; Onteniente, S; Jullien, V; Montange, D; Piedoux, S; Thiery-Vuillemin, A; Delroeux, D; Pili-Floury, S.; Guardiola, E; Combe, M.; Muret, P.; Nerich, V; Heyd, B; Chauffert, B

    2011-01-01

    Background: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. Methods: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. Results: Epinephrine halves...

  3. Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

    Science.gov (United States)

    Krukiewicz, Katarzyna; Zak, Jerzy K

    2016-05-01

    Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  5. Mechanisms for enhanced performance of platinum-based electrocatalysts in proton exchange membrane fuel cells.

    Science.gov (United States)

    Su, Liang; Jia, Wenzhao; Li, Chang-Ming; Lei, Yu

    2014-02-01

    As a new generation of power sources, fuel cells have shown great promise for application in transportation. However, the expensive catalyst materials, especially the cathode catalysts for oxygen reduction reaction (ORR), severely limit the widespread commercialization of fuel cells. Therefore, this review article focuses on platinum (Pt)-based electrocatalysts for ORR with better catalytic performance and lower cost. Major breakthroughs in the improvement of activity and durability of electrocatalysts are discussed. Specifically, on one hand, the enhanced activity of Pt has been achieved through crystallographic control, ligand effect, or geometric effect; on the other hand, improved durability of Pt-based cathode catalysts has been realized by means of the incorporation of another noble metal or the morphological control of nanostructures. Furthermore, based on these improvement mechanisms, rationally designed Pt-based nanoparticles are summarized in terms of different synthetic strategies such as wet-chemical synthesis, Pt-skin catalysts, electrochemically dealloyed nanomaterials, and Pt-monolayer deposition. These nanoparticulate electrocatalysts show greatly enhanced catalytic performance towards ORR, aiming not only to outperform the commercial Pt/C, but also to exceed the US Department of Energy 2015 technical target ($30/kW and 5000 h).

  6. Acetaldehyde behavior over platinum based catalyst in hydrogen stream generated by ethanol reforming

    Energy Technology Data Exchange (ETDEWEB)

    de Lima, Adriana F.F. [Laboratorio de Catalise, Instituto Nacional de Tecnologia, Av. Venezuela 82/507, 20081-310 Rio de Janeiro, RJ (Brazil); Instituto de Quimica e INOG (Instituto Nacional de Oleo Gas), UERJ-CNPq, FAPERJ, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier, 524, 20550-900 Rio de Janeiro, RJ (Brazil); Colman, Rita C. [Departamento de Engenharia Quimica e de Petroleo, Universidade Federal Fluminense, Av. Passos da Patria, 156/bl E/240, 24210-240 Niteroi, RJ (Brazil); Zotin, Fatima M.Z. [Instituto de Quimica e INOG (Instituto Nacional de Oleo Gas), UERJ-CNPq, FAPERJ, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier, 524, 20550-900 Rio de Janeiro, RJ (Brazil); CETEM-MCT, Av. Pedro Calmon, 900, Cidade Universitaria, 21941-908 Rio de Janeiro, RJ (Brazil); Appel, Lucia G. [Laboratorio de Catalise, Instituto Nacional de Tecnologia, Av. Venezuela 82/507, 20081-310 Rio de Janeiro, RJ (Brazil)

    2010-12-15

    Due to the greenhouse effect, hydrogen production from bioethanol reforming is a very important subject in heterogeneous catalysis research. Pt based catalysts are employed in H{sub 2} purification processes and also as electrocatalysts of PEM (''Proton Exchange Membrane'') fuel cells. Hydrogen obtained from ethanol reforming may contain, as contaminants, acetaldehyde and small amounts of CO. This aldehyde can be decarbonylated on Pt based catalysts generating carbon monoxide and methane, rendering the hydrogen purification more challenging. Moreover, acetaldehyde might also change the electrocatalyst behavior. Therefore, this contribution aims at studying the acetaldehyde behavior in the presence of platinum based catalysts in hydrogen atmosphere. The Pt/SiO{sub 2}, Pt/USY catalysts and an electrocatalyst were characterized by n-butylamine, H{sub 2} and CO{sub 2} adsorption, ATG/DTG measurements and cyclohexane dehydrogenation reaction. It was observed that the acid-basic properties of the supports promote condensation reactions. When in contact with Pt based catalysts, acetaldehyde undergoes C-C and C=O bond scissions. The former occurs at a wide range of temperatures, whereas the latter only at low temperatures (<200 C). The C-C bond scission (decarbonylation) produces methane and CO. The C=O bond scission generates carbon residues on the catalyst as well as oxygen species, which in turn is able to eliminate CO from the catalytic surface. The data also show that decarbonylation is not a structure-sensitive reaction. (author)

  7. Hydroisomerization of Ethylbenzene on Mordenite-Based Bifunctional Catalysts with Different Platinum Contents

    Directory of Open Access Journals (Sweden)

    Fernandes L.D.

    1998-01-01

    Full Text Available A commercial Na-mordenite sample underwent ion exchange with HCl. The ion-exchanged sample was sequentially submitted to hydrothermal treatments at 823, 873 and 923 K, each followed by acid leaching of the extraframework alumina (EFAL generated. Six mordenite samples, presenting different framework and extraframework compositions, were obtained. These samples were used to prepare bifunctional catalysts by mixing them with Pt/Al2O3 in different proportions. The generated samples presented distinct platinum contents and were tested in the hydroisomerization reaction of ethylbenzene. A maximum xylene selectivity at about 0.45 wt% of platinum was observed. Normally, the total activity increased as the platinum content increased; this effect was more pronounced in the samples which presented lower mesoporosity. The most dealuminated sample, which presented a high mesoporosity, did not show any change in activity with the increase in platinum content.

  8. Intramolecular triplet energy transfer in anthracene-based platinum acetylide oligomers.

    Science.gov (United States)

    Li, Yongjun; Köse, Muhammet E; Schanze, Kirk S

    2013-08-01

    Platinum acetylide oligomers that contain an anthracene moiety have been synthesized and subjected to photophysical characterization. Spectroscopic measurement and DFT calculations reveal that both the singlet and triplet energy levels of the anthracene segment are lower than those of the platinum acetylide segment. Thus, the platinum acetylide segment acts as a sensitizer to populate the triplet state of the anthrancene segment via intramolecular triplet-triplet energy transfer. The objective of this work is to understand the mechanisms of energy-transfer dynamics in these systems. Fluorescence quenching and the dominant triplet absorption that arises from the anthracene segment in the transient absorption spectrum of Pt4An give clear evidence that energy transfer adopts an indirect mechanism, which begins with singlet-triplet energy transfer from the anthracene segment to the platinum acetylide segment followed by triplet-triplet energy transfer to the anthracene segment.

  9. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

    NARCIS (Netherlands)

    Frielink, L.M.; Pijlman, B.M.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2016-01-01

    BACKGROUND: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. METHODS: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The perc

  10. Prevention of chemotherapy-induced peripheral neuropathy by the small-molecule inhibitor pifithrin-mu

    NARCIS (Netherlands)

    Krukowski, Karen; Nijboer, Cora H.; Huo, XiaoJiao; Kavelaars, Annemieke; Heijnen, Gobi J.

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatmen

  11. Nano-structured Platinum-based Catalysts for the Complete Oxidation of Ethylene Glycol and Glycerol

    Science.gov (United States)

    Falase, Akinbayowa

    Direct alcohol fuel cells are a viable alternative to the traditional hydrogen PEM fuel cell. Fuel versatility, integration with existing distribution networks, and increased safety when handling these fuels increases their appeal for portable power applications. In order to maximize their utility, the liquid fuel must be fully oxidized to CO2 so as to harvest the full amount of energy. Methanol and ethanol are widely researched as potential fuels to power these devices, but methanol is a toxic substance, and ethanol has a much lower energy density than other liquids such as gasoline or glucose. Oxidation of complex fuels is difficult to realize, due to difficulty in breaking carbon-carbon bonding and poisoning of the catalysts by oxidative byproducts. In order to achieve the highest efficiency, an anode needs to be engineered in such a way as to maximize activity while minimizing poisoning effects of reaction byproducts. We have engineered an anode that uses platinum-based catalysts that is capable of completely oxidizing ethylene glycol and glycerol in neutral and alkaline media with little evidence of CO poisoning. We have constructed a hybrid anode consisting of a nano-structured PtRu electrocatayst with an NAD-dependent alcohol dehydrogenase for improved oxidation of complex molecules. A nano-structured PtRu catalyst was used to oxidize ethylene glycol and glycerol in neutral media. In situ infrared spectroscopy was used to verify complete oxidation via CO2 generation. There was no evidence of poisoning by CO species. A pH study was performed to determine the effect of pH on oxidative current. The peak currents did not trend at 60 mV/pH unit as would be expected from the Nernst equation, suggesting that adsorption of fuel to the surface of the electrode is not an electron-transfer step. We synthesized nano-structured PtRu, PtSn, and PtRuSn catalysts for oxidation of ethylene glycol and glycerol in alkaline media. The PtRu electrocatalyst the highest oxidative

  12. Synthesis, characterization, and biological evaluation of Schiff base-platinum(II) complexes.

    Science.gov (United States)

    Shiju, C; Arish, D; Bhuvanesh, N; Kumaresan, S

    2015-06-15

    The platinum complexes of Schiff base ligands derived from 4-aminoantipyrine and a few substituted aldehydes were synthesized and characterized by elemental analysis, mass, (1)H NMR, IR, electronic spectra, molar conductance, and powder XRD. The structure of one of the ligands L5 was confirmed by a single crystal XRD analysis. The Schiff base ligand crystallized in the triclinic, space group P-1 with a=7.032(2)Ǻ, b=9.479(3)Ǻ, c=12.425(4)Ǻ, α=101.636(3)°, β=99.633(3)°, γ=94.040(3)°, V=795.0(4)Ǻ(3), Z=2, F(000)=352, Dc=1.405 mg/m(3), μ=0.099 mm(-1), R=0.0378, and wR=0.0967. The spectral results show that the Schiff base ligand acts as a bidentate donor coordinating through the azomethine nitrogen and the carbonyl oxygen atoms. The geometrical structures of these complexes are found to be square planar. Antimicrobial studies indicate that these complexes exhibit better activity than the ligand. The anticancer activities of the complexes have also been studied towards human cervical cancer cell line (HeLa), Colon Cancer Cells (HCT116) and Epidermoid Carcinoma Cells (A431) and it was found that the [Pt(L3)Cl2] complex is more active.

  13. High pathologic complete remission rate from induction docetaxel, platinum and fluorouracil (DCF) combination chemotherapy for locally advanced esophageal and junctional cancer.

    Science.gov (United States)

    Noronha, Vanita; Joshi, Amit; Jandyal, Sunny; Jambhekar, Nirmala; Prabhash, Kumar

    2014-09-01

    Adding docetaxel to the cisplatin/5-fluorouracil induction regimen for locally advanced esophageal and GEJ cancer may increase the pathologic complete remission (pCR) rate, leading to an improved outcome. Institutional ethics committee approved the protocol of retrospective analysis of patients with locally advanced esophageal and GEJ carcinoma, who received 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil (DCF) induction chemotherapy with primary growth factors and prophylactic antibiotics. Following chemotherapy, a restaging scan was performed. If disease was deemed resectable, surgery was performed. Between February 2010 and October 2013, 31 patients received induction DCF. Ninety-four percent patients had squamous histology. Response rate was 81 %: complete remission (CR)-23 % and partial remission-58 %. Eighty-seven percent patients underwent surgery; R0 resection rate was 67 %. pCR occurred in 26 %. Common grade 3/4 toxicities included anemia-23 %, neutropenia-42 %, febrile neutropenia-39 %, diarrhea-39 %, hyponatremia-55 % and hypokalemia-39 %. There were no toxic deaths. At a median follow-up of 34 months (95 % CI 31.3-36.6), estimated median progression-free survival (PFS) was 27 months (95 % CI 11-39) and the overall survival (OS) at 1 year, 2 years and 3 years was 80, 68 and 55 %, respectively. Patients who attained pCR had a significant longer PFS and OS; median PFS and OS were not reached in patients with pCR and were 15 months (95 %CI 8.4-21.5 months), P = 0.012 and 25 months (95 %CI 10.3-39.7), P = 0.023, respectively, in patients who did not attain a pCR. DCF induction chemotherapy leads to pCR of 26 %, which rivals that obtained from chemoradiotherapy. Toxicity is substantial but manageable with adequate supportive care.

  14. Synthesis and Characterization of Phenothiazine-Based Platinum(II)-Acetylide Photosensitizers for Efficient Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Siu, Chi-Ho; Lee, Lawrence Tien Lin; Yiu, Sze-Chun; Ho, Po-Yu; Zhou, Panwang; Ho, Cheuk-Lam; Chen, Tao; Liu, Jianyong; Han, Keli; Wong, Wai-Yeung

    2016-03-07

    Three new unsymmetrical phenothiazine-based platinum(II) bis(acetylide) complexes PT1-PT3 with different electron-donating arylacetylide ligands were synthesized and characterized. Their photophysical, electrochemical, and photovoltaic properties have been fully investigated and the density functional theory (DFT) calculations have been carried out. Under AM 1.5 irradiation (100 mW cm(-2)), the PT1-based dye-sensitized solar cell (DSSC) device exhibited an attractive power conversion efficiency (η) up to 5.78 %, with a short-circuit photocurrent density (J(sc)) of 10.98 mA cm(-2), an open-circuit photovoltage (V(oc)) of 0.738 V, and a fill factor (ff) of 0.713. These findings provide strong evidence that platinum-acetylide complexes have great potential as promising photosensitizers in DSSC applications.

  15. Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

    OpenAIRE

    SHI, MINGHAN; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-01-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by facto...

  16. Electrocatalytic (Bio)Nanostructures Based on Polymer-Grafted Platinum Nanoparticles for Analytical Purpose.

    Science.gov (United States)

    Gal, François; Challier, Lylian; Cousin, Fabrice; Perez, Henri; Noel, Vincent; Carrot, Geraldine

    2016-06-15

    Functionalized platinum nanoparticles (PtNPs) possess electrocatalytic properties toward H2O2 oxidation, which are of great interest for the construction of electrochemical oxidoreductase-based sensors. In this context, we have shown that polymer-grafted PtNPs could efficiently be used as building bricks for electroactive structures. In the present work, we prepared different 2D-nanostructures based on these elementary bricks, followed by the subsequent grafting of enzymes. The aim was to provide well-defined architectures to establish a correlation between their electrocatalytic properties and the arrangement of building bricks. Two different nanostructures have been elaborated via the smart combination of surface initiated-atom transfer radical polymerization (SI-ATRP), functionalized PtNPs (Br-PtNPs) and Langmuir-Blodgett (LB) technique. The first nanostructure (A) has been elaborated from LB films of poly(methacrylic acid)-grafted PtNPs (PMAA-PtNPs). The second nanostructure (B) consisted in the elaboration of polymer brushes (PMAA brushes) from Br-PtNPs LB films. In both systems, grafting of the glucose oxidase (GOx) has been performed directly to nanostructures, via peptide bonding. Structural features of nanostructures have been carefully characterized (compression isotherms, neutron reflectivity, and profilometry) and correlated to their electrocatalytic properties toward H2O2 oxidation or glucose sensing.

  17. Initial management of primary mediastinal seminoma: radiotherapy or cisplatin-based chemotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Le Chevalier, T.; Ruffie, P.; Rixe, O. [Department of Medical Oncology, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex (France); Wibault, P. [Department of Radiotherapy, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex (France); Theodore, C. [Department of Medical Oncology, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex (France); Terrier-Lacombe, M.-J. [Department of Pathology, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex (France); Droz, J.-P.; Culine, S.; Fizazi, K. [Department of Medical Oncology, Institut Gustave-Roussy, 39 rue Camille-Desmoulins, 94805 Villejuif Cedex (France)

    1998-02-01

    Primary mediastinal seminoma is an uncommon neoplasm, the optimal management of which is still debated. Radiotherapy produces a 65% disease-free survival rate. We assess whether these results have been improved with the advent of cisplatin-based chemotherapy. Data from 14 patients treated at the Institut Gustave-Roussy were reviewed. 9 had received cisplatin-based chemotherapy (Group 1): their outcome was compared with that of 5 patients treated with radiotherapy without chemotherapy (Group 2). We also reviewed data from the English literature using strict criteria, and report results concerning patients who received cisplatin-based chemotherapy and those who received radiotherapy. 8 of the 9 patients (89%) in Group 1 are long-term disease-free survivors and only 3 of 5 patients in Group 2. The patient who died in Group 1 was the only one who refused surgical resection of residual masses after chemotherapy. The review of the literature revealed that 59 of 68 (87%) patients initially managed with cisplatin- or carboplatin-based chemotherapy and for whom sufficient data are available, are long-term survivors and free of disease. Some of these patients had also received radiotherapy. Only 64 of 103 (62%) treated with thoracic radiotherapy without chemotherapy were long-term disease-free survivors. The disease-free survival rate of 51 patients who received cisplatin-based chemotherapy (excluding those who received carboplatin) was 86%. The difference in survival between patients administered cisplatin-based chemotherapy and those who underwent radiotherapy is apparently not due to unbalanced prognostic factors, the effect of time or non-specific medical management. We conclude that cisplatin-based chemotherapy allows long-term disease-free survival in approximately 85% of patients. These results seem to be higher than those obtained without cisplatin-based chemotherapy. However, a randomised study is required for definitive conclusions, but it is very unlikely that

  18. Reinforcement learning-based control of drug dosing for cancer chemotherapy treatment.

    Science.gov (United States)

    Padmanabhan, Regina; Meskin, Nader; Haddad, Wassim M

    2017-08-16

    The increasing threat of cancer to human life and the improvement in survival rate of this disease due to effective treatment has promoted research in various related fields. This research has shaped clinical trials and emphasized the necessity to properly schedule cancer chemotherapy to ensure effective and safe treatment. Most of the control methodologies proposed for cancer chemotherapy scheduling treatment are model-based. In this paper, a reinforcement learning (RL)-based, model-free method is proposed for the closed-loop control of cancer chemotherapy drug dosing. Specifically, the Q-learning algorithm is used to develop an optimal controller for cancer chemotherapy drug dosing. Numerical examples are presented using simulated patients to illustrate the performance of the proposed RL-based controller. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Platinum(II)-Based Metallo-Supramolecular Polymer with Controlled Unidirectional Dipoles for Tunable Rectification.

    Science.gov (United States)

    Chakraborty, Chanchal; Pandey, Rakesh K; Hossain, Md Delwar; Futera, Zdenek; Moriyama, Satoshi; Higuchi, Masayoshi

    2015-09-01

    A platinum(II)-based, luminescent, metallo-supramolecular polymer (PolyPtL1) having an inherent dipole moment was synthesized via complexation of Pt(II) ions with an asymmetric ligand L1, containing terpyridyl and pyridyl moieties. The synthesized ligand and polymer were well characterized by various NMR techniques, optical spectroscopy, and cyclic voltammetry studies. The morphological study by atomic force microscopy revealed the individual and assembled polymer chains of 1-4 nm height. The polymer was specifically attached on Au-electrodes to produce two types of film (films 1 and 2) in which the polymer chains were aligned with their dipoles in opposite directions. The Au-surface bounded films were characterized by UV-vis, Raman spectroscopy, cyclic voltammetry, and atomic force microscopy study. The quantum mechanical calculation determined the average dipole moment for each monomer unit in PolyPtL1 to be about 5.8 D. The precise surface derivatization permitted effective tuning of the direction dipole moment, as well as the direction of rectification of the resulting polymer-attached molecular diodes. Film 1 was more conductive in positive bias region with an average rectification ratio (RR = I(+4 V)/I(-4 V)) ≈ 20, whereas film 2 was more conducting in negative bias with an average rectification ratio (RR = I(-4 V)/I(+4 V)) ≈ 18.

  20. Aged nano-structured platinum based catalyst: effect of chemical treatment on adsorption and catalytic activity.

    Science.gov (United States)

    Shim, Wang Geun; Nahm, Seung Won; Park, Hyuk Ryeol; Yun, Hyung Sun; Seo, Seong Gyu; Kim, Sang Chai

    2011-02-01

    To examine the effect of chemical treatment on the adsorption and catalytic activity of nanostructured platinum based catalyst, the aged commercial Pt/AC catalyst was pretreated with sulfuric acid (H2SO4) and a cleaning agent (Hexane). Several reliable methods such as nitrogen adsorption, X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and inductively coupled plasma (ICP) were employed to characterize the aged Pt/AC catalyst and its chemically pretreated Pt/AC catalysts. The catalytic and adsorption activities of nano-structured heterogeneous Pt/AC catalyst were investigated on the basis of toluene oxidation and adsorption isotherm data. In addition, the adsorption isotherms of toluene were used to calculate the adsorption energy distribution functions for the parent catalyst and its pre-treated nano-structured Pt/AC catalysts. It was found that sulfuric acid aqueous treatment can enhance the catalytic performance of aged Pt/AC catalyst toward catalytic oxidation of toluene. It was also shown that a comparative analysis of the energy distribution functions for nano-structured Pt/AC catalysts as well as the pore size distribution provides valuable information about their structural and energetic heterogeneity.

  1. Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types

    Science.gov (United States)

    Al-Adawi, Kawther; Al-Nabhani, Abdurahman; Al-Kindi, Mohamed

    2017-01-01

    Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.

  2. Estimation of an optimal chemotherapy utilisation rate for cancer: setting an evidence-based benchmark for quality cancer care.

    Science.gov (United States)

    Jacob, S A; Ng, W L; Do, V

    2015-02-01

    There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications.

  3. Synthesis, characterization and electrochemical studies of novel platinum-based nanomaterials

    Science.gov (United States)

    Wang, Jingpeng

    2009-12-01

    Platinum (Pt) as well as its alloys represent some of the most efficient catalyst materials among intermetallic compounds and alloys. An important clue throughout this work is the development of a desired synthetic approach of Pt-based nanomaterials---a one-step hydrothermal co-reduction of inorganic metal precursors. Slight modifications in experimental conditions have led to the production of Pt-based nanostructured materials with two distinct morphologies: (i) three-dimensional (3D) nanoporous Pt-M networks (M= Ru, Ir, Pb, Pd) when formaldehyde is used as a reducing agent; and (ii) 3D intermetallic Pt-M nanodendrites (M= Au, Pb, Bi or Pd) when formate ligands are present as multi-functional reagents in the hydrothermal process. Those as-synthesized Pt-based nanoporous catalysts not only possess significantly high surface areas, but also exhibit superb electrocatalytic activities towards the electrochemical oxidation of methanol and formic acid. Among them, the nanoporous PtPb networks were further tested towards the electro-oxidation of glucose. Voltammetric and amperometric results demonstrate that the PtPb electrodes have strong and sensitive current responses to the incremental glucose concentrations, and are capable of sensing glucose with excellent selectivity in neutral media. In the case of synthesizing Pt-based nanodendritic materials, ammonium formate and formic acid were used as multi-functional reagents in the hydrothermal-assisted fabrication of alloyed PtAu and PtPb nanodendrites, respectively. Electrochemical studies reveal that both PtAu and PtPb nanodendrites exhibit exceptionally high electrocatalytic activities in formic acid oxidation owing to their unique alloyed intermetallic crystal structures. The proposed coordination and co-reduction alloying mechanism together with the foreign particle-induced dendritic growth mechanism have been further proved to be universal for fabricating a wide range of intermetallic nanodendrites, including

  4. A Case of Neurotoxicity Following 5-Fluorouracil-based Chemotherapy

    Science.gov (United States)

    Ki, Seung Seog; Jeong, Jin Mo; Kim, Seong Ho; Jeong, Sook Hyang; Lee, Jin Hyuk; Han, Chul Ju; Kim, You Cheol; Lee, Jhin Oh; Hong, Young Joon

    2002-01-01

    5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent. However, its neurotoxicity is rare and not well recognized. We report a case of 5-FU neurotoxicity with organic brain syndrome and progression to multifocal leukoencephalopathy in a 44-year-old male patient having malignant gastrointestinal stromal tumor. 5-FU-induced neurotoxicity should, therefore, be considered as an important differential diagnosis in cancer patients with neurological abnormality and history of chemotherapy. PMID:12014219

  5. Starvation Based Differential Chemotherapy: A Novel Approach for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Sidra Naveed

    2014-11-01

    Full Text Available Cancer patients undergoing chemotherapy treatment are advised to increase food intake to overcome the therapy-induced side effects, and weight loss. Dietary restriction is known to slow down the aging process and hence reduce age-related diseases such as cancer. Fasting or short-term starvation is more effective than dietary restriction to prevent cancer growth since starved cells switch off signals for growth and reproduction and enter a protective mode, while cancer cells, being mutated, are not sensitized by any external growth signals and are not protected against any stress. This phenomenon is known as differential stress resistance (DSR. Nutrient signaling pathways involving growth hormone/insulin-like growth factor-1 axis and its downstream effectors, play a key role in DSR in response to starvation controlling the other cell maintenance systems, such as autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells lacking these effectors are better protected against oxidative stress compared to normal cells. In the same way, starvation protects many cell lines and mice against high-dose chemotherapeutic drugs. According to a series of studies, fasting results in overall reduction in chemotherapy side effects in cancer patients. Data shows that starvation-dependent differential chemotherapy is safe, feasible and effective in cancer treatment, but the possible side effects of starvation limit its efficacy. However, further studies and clinical trials may result in its implementation in cancer treatment.

  6. Tumour chemotherapy strategy based on impulse control theory.

    Science.gov (United States)

    Ren, Hai-Peng; Yang, Yan; Baptista, Murilo S; Grebogi, Celso

    2017-03-06

    Chemotherapy is a widely accepted method for tumour treatment. A medical doctor usually treats patients periodically with an amount of drug according to empirical medicine guides. From the point of view of cybernetics, this procedure is an impulse control system, where the amount and frequency of drug used can be determined analytically using the impulse control theory. In this paper, the stability of a chemotherapy treatment of a tumour is analysed applying the impulse control theory. The globally stable condition for prescription of a periodic oscillatory chemotherapeutic agent is derived. The permanence of the solution of the treatment process is verified using the Lyapunov function and the comparison theorem. Finally, we provide the values for the strength and the time interval that the chemotherapeutic agent needs to be applied such that the proposed impulse chemotherapy can eliminate the tumour cells and preserve the immune cells. The results given in the paper provide an analytical formula to guide medical doctors to choose the theoretical minimum amount of drug to treat the cancer and prevent harming the patients because of over-treating.This article is part of the themed issue 'Horizons of cybernetical physics'.

  7. Nanoengineering of Ruthenium and Platinum-based Nanocatalysts by Continuous-Flow Chemistry for Renewable Energy Applications

    KAUST Repository

    AlYami, Noktan Mohammed

    2017-04-15

    This thesis presents an integrated study of nanocatalysts for heterogenous catalytic and electrochemical processes using pure ruthenium (Ru) with mixed-phase and platinum-based nanomaterials synthesized by continuous-flow chemistry. There are three major challenges to the application of nanomaterials in heterogenous catalytic reactions and electrocatalytic processes in acidic solution. These challenges are the following: (i) controlling the size, shape and crystallography of nanoparticles to give the best catalytic properties, (ii) scaling these nanoparticles up to a commercial quantity (kg per day) and (iii) making stable nanoparticles that can be used catalytically without degrading in acidic electrolytes. Some crucial limitations of these nanostructured materials in energy conversion and storage applications were overcome by continuous-flow chemistry. By using a continuous-flow reactor, the creation of scalable nanoparticle systems was achieved and their functionality was modified to control the nanoparticles’ physical and chemical characteristics. The nanoparticles were also tested for long-term stability, to make sure these nanoparticles were feasible under realistic working conditions. These nanoparticles are (1) shape- and crystallography-controlled ruthenium (Ru) nanoparticles, (2) size-controlled platinum-metal (Pt-M= nickel (Ni) & copper (Cu)) nanooctahedra (while maintaining morphology) and (3) core-shell platinum@ruthenium (Pt@Ru) nanoparticles where an ultrathin ruthenium shell was templated onto the platinum core. Thus, a complete experimental validation of the formation of a scalable amount of these nanoparticles and their catalytic activity and stability towards the oxygen evolution reaction (OER) in acid medium, hydrolysis of ammonia borane (AB) along with plausible explanations were provided.

  8. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

    OpenAIRE

    Arrieta, Ó.; Medina, L A; Estrada-Lobato, E; Hernández-Pedro, N; Villanueva-Rodríguez, G; Martínez-Barrera, L.; Macedo, E O; López-Rodríguez, V; Motola-Kuba, D; Corona-Cruz, J F

    2012-01-01

    Background: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration. Methods: A total of 38 patients w...

  9. Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Lund, Bente

    and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human...... of first or second line platinum-based chemotherapy. Only patients with maximum 2 prior lines of chemotherapy, measurable disease by CA125 criteria and with KRAS wild type are eligible. Patients are treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2 day 1, every 4 weeks. Tumor...... to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue...

  10. The association of Raynaud's syndrome with cisplatin-based chemotherapy - a meta-analysis.

    Science.gov (United States)

    Mohokum, Melvin; Hartmann, Peter; Schlattmann, Peter

    2012-10-01

    Vasospastic disorders of the digital circulation such as the Raynaud's syndrome (RS) are known side-effects of treatment of cisplatin-based chemotherapy. The prevalence of RS in patients during treatment with cisplatin-based chemotherapy is not well-defined. The objective of this paper was to assess the prevalence of RS in patients receiving cisplatin-based chemotherapy - a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and patients receiving cisplatin-based chemotherapy. The studies provided sufficient data to estimate the prevalence of RS in patients receiving cisplatin-based chemotherapy. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication and latitude. 24 eligible studies, contributing data on 2749 subjects, were included in this meta-analysis. For RS in patients receiving cisplatin-based chemotherapy a pooled prevalence of 24% and 95% CI (0.175, 0.313) was obtained. A mixture model analysis found four latent classes. Statistically, publication bias was not present (p-value 0.74). The meta-regression indicated that the odds ratio increased when the latitude increased, too (p-value 0.011). Despite some heterogeneity there is a possible indication of an association between RS and patients receiving cisplatin-based chemotherapy. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  11. Graphene-Supported Platinum Catalyst-Based Membrane Electrode Assembly for PEM Fuel Cell

    Science.gov (United States)

    Devrim, Yilser; Albostan, Ayhan

    2016-08-01

    The aim of this study is the preparation and characterization of a graphene-supported platinum (Pt) catalyst for proton exchange membrane fuel cell (PEMFC) applications. The graphene-supported Pt catalysts were prepared by chemical reduction of graphene and chloroplatinic acid (H2PtCl6) in ethylene glycol. X-ray powder diffraction, thermogravimetric analysis (TGA) and scanning electron microscopy have been used to analyze structure and surface morphology of the graphene-supported catalyst. The TGA results showed that the Pt loading of the graphene-supported catalyst was 31%. The proof of the Pt particles on the support surfaces was also verified by energy-dispersive x-ray spectroscopy analysis. The commercial carbon-supported catalyst and prepared Pt/graphene catalysts were used as both anode and cathode electrodes for PEMFC at ambient pressure and 70°C. The maximum power density was obtained for the Pt/graphene-based membrane electrode assembly (MEA) with H2/O2 reactant gases as 0.925 W cm2. The maximum current density of the Pt/graphene-based MEA can reach 1.267 and 0.43 A/cm2 at 0.6 V with H2/O2 and H2/air, respectively. The MEA prepared by the Pt/graphene catalyst shows good stability in long-term PEMFC durability tests. The PEMFC cell voltage was maintained at 0.6 V without apparent voltage drop when operated at 0.43 A/cm2 constant current density and 70°C for 400 h. As a result, PEMFC performance was found to be superlative for the graphene-supported Pt catalyst compared with the Pt/C commercial catalyst. The results indicate the graphene-supported Pt catalyst could be utilized as the electrocatalyst for PEMFC applications.

  12. Surface structured platinum electrodes for the electrochemical reduction of carbon dioxide in imidazolium based ionic liquids.

    Science.gov (United States)

    Hanc-Scherer, Florin A; Montiel, Miguel A; Montiel, Vicente; Herrero, Enrique; Sánchez-Sánchez, Carlos M

    2015-10-01

    The direct CO2 electrochemical reduction on model platinum single crystal electrodes Pt(hkl) is studied in [C2mim(+)][NTf2(-)], a suitable room temperature ionic liquid (RTIL) medium due to its moderate viscosity, high CO2 solubility and conductivity. Single crystal electrodes represent the most convenient type of surface structured electrodes for studying the impact of RTIL ion adsorption on relevant electrocatalytic reactions, such as surface sensitive electrochemical CO2 reduction. We propose here based on cyclic voltammetry and in situ electrolysis measurements, for the first time, the formation of a stable adduct [C2mimH-CO2(-)] by a radical-radical coupling after the simultaneous reduction of CO2 and [C2mim(+)]. It means between the CO2 radical anion and the radical formed from the reduction of the cation [C2mim(+)] before forming the corresponding electrogenerated carbene. This is confirmed by the voltammetric study of a model imidazolium-2-carboxylate compound formed following the carbene pathway. The formation of that stable adduct [C2mimH-CO2(-)] blocks CO2 reduction after a single electron transfer and inhibits CO2 and imidazolium dimerization reactions. However, the electrochemical reduction of CO2 under those conditions provokes the electrochemical cathodic degradation of the imidazolium based RTIL. This important limitation in CO2 recycling by direct electrochemical reduction is overcome by adding a strong acid, [H(+)][NTf2(-)], into solution. Then, protons become preferentially adsorbed on the electrode surface by displacing the imidazolium cations and inhibiting their electrochemical reduction. This fact allows the surface sensitive electro-synthesis of HCOOH from CO2 reduction in [C2mim(+)][NTf2(-)], with Pt(110) being the most active electrode studied.

  13. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

  14. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kayo OSAWA

    2009-08-01

    Full Text Available The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR

  15. Mechanistic basis for overcoming platinum resistance using copper chelating agents.

    Science.gov (United States)

    Liang, Zheng D; Long, Yan; Tsai, Wen-Bin; Fu, Siqing; Kurzrock, Razelle; Gagea-Iurascu, Mihai; Zhang, Fan; Chen, Helen H W; Hennessy, Bryan T; Mills, Gordon B; Savaraj, Niramol; Kuo, Macus Tien

    2012-11-01

    Platinum-based antitumor agents are widely used in cancer chemotherapy. Drug resistance is a major obstacle to the successful use of these agents because once drug resistance develops, other effective treatment options are limited. Recently, we conducted a clinical trial using a copper-lowering agent to overcome platinum drug resistance in ovarian cancer patients and the preliminary results are encouraging. In supporting this clinical study, using three pairs of cisplatin (cDDP)-resistant cell lines and two ovarian cancer cell lines derived from patients who had failed in platinum-based chemotherapy, we showed that cDDP resistance associated with reduced expression of the high-affinity copper transporter (hCtr1), which is also a cDDP transporter, can be preferentially resensitized by copper-lowering agents because of enhanced hCtr1 expression, as compared with their drug-sensitive counterparts. Such a preferential induction of hCtr1 expression in cDDP-resistant variants by copper chelation can be explained by the mammalian copper homeostasis regulatory mechanism. Enhanced cell-killing efficacy by a copper-lowering agent was also observed in animal xenografts bearing cDDP-resistant cells. Finally, by analyzing a public gene expression dataset, we found that ovarian cancer patients with elevated levels of hCtr1 in their tumors, but not ATP7A and ATP7B, had more favorable outcomes after platinum drug treatment than those expressing low hCtr1 levels. This study reveals the mechanistic basis for using copper chelation to overcome cDDP resistance in clinical investigations.

  16. Merensky pillar strength formulae based on back-analysis of pillar failures at Impala Platinum

    CSIR Research Space (South Africa)

    Watson, BP

    2008-08-01

    Full Text Available The Bushveld platinum group metal deposits are two distinct, shallow-dipping stratiform tabular orebodies and strike for many hundreds of kilometres. Mining is extensive, with depths ranging from close-to-surface to 2 000 m. The mining method is a...

  17. Application of liposomal technologies for delivery of platinum analogs in oncology

    OpenAIRE

    Liu D; He C; Wang AZ; Lin W

    2013-01-01

    Demin Liu1, Chunbai He1, Andrew Z Wang2, Wenbin Lin1 1Department of Chemistry, University of Chicago, Chicago, IL, USA; 2Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, ...

  18. Kinetic study and growth behavior of template-based electrodeposited platinum nanotubes controlled by overpotential

    Energy Technology Data Exchange (ETDEWEB)

    Yousefi, E. [Department of Materials Science and Engineering, Sharif University of Technology, Azadi Ave., P.O.Box 11155-9466, Tehran (Iran, Islamic Republic of); Dolati, A., E-mail: dolati@sharif.edu [Department of Materials Science and Engineering, Sharif University of Technology, Azadi Ave., P.O.Box 11155-9466, Tehran (Iran, Islamic Republic of); Imanieh, I. [Department of Materials Science and Engineering, Sharif University of Technology, Azadi Ave., P.O.Box 11155-9466, Tehran (Iran, Islamic Republic of); Yashiro, H.; Kure-Chu, S.-Z. [Department of Chemistry and Bioengineering, Faculty of Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate, 020-8551 (Japan)

    2017-02-01

    Platinum nanotubes (PtNTs) are fabricated by potentiostatic electrodeposition at various overpotentials (−200 up to −400 mV versus SCE) in polycarbonate templates (PCTs) with pore diameter of 200 nm in a solution containing 5 mM H{sub 2}PtCl{sub 6} and 0.1 M H{sub 2}SO{sub 4}. The synthesized PtNTs are characterized by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The electrochemical growth mechanism within nanoscopic pores and the relationship between morphological variations and kinetic parameters are investigated for the first time. It is shown that more porous structure of nanotubes forms at high overpotentials possibly due to preferably nucleation. The kinetics of electrodeposition process is studied by electrochemical techniques such as voltammetry and chronoamperometry. The linear diffusion coefficient at the early stage of the deposition and the radial diffusion coefficients at steady state regime are calculated as D = 8.39 × 10{sup −5} and 2.33–13.26 × 10{sup −8} cm{sup 2}/s, respectively. The synthesized PtNT electrode is tested as electrocatalyst for hydrogen peroxide oxidation in phosphate buffer solution (PBS) and shows a sensitivity as high as 2.89 mA per 1 μM that is an indication to its enlarged electrochemical surface area. - Highlights: • PtNT is electrodeposited in a 3-aminopropyltrimethoxysilane-modified PCT. • The electrochemical growth mechanism within nanoscopic pores is discussed. • The kinetics of PtNT electrodeposition is studied based on models for UME arrays. • Relationship between morphological variations vs. kinetic parameters is studied.

  19. Energy basis of recognition of base pair for platinum-based antitumour drug ZD0473 and cisplatin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the mixed method of molecular mechanics and quantum chemistry, HF/lanl2dz// MM/uff and B3LYP/lanl2dz//6-31G*, are used to investigate the differences between four types of GG, 3′AG5′, 3′GA5′, and AA complexes, which are formed from four discrete DNA fragments recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments and high antitumour activity of ZD0473. The main reason for easier forming of 3′GA5′ complex than the 3′AG5′ one is that the drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the con- figuration transformation from such monoligand compound to the bi-ligand one is limited.

  20. Enersy basis of recognition of base pair for platinum-based antitumour drug ZD0473 and cisplatin

    Institute of Scientific and Technical Information of China (English)

    HAO Lan; LI XiChen; TAN HongWei; CHEN GuangJu; JIA MuXin

    2008-01-01

    Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the mixed method of molecular mechanics and quantum chemistry, HF/lan12dz//MM/uff and B3LYP/lan12dz//6-31G*, are used to investigate the differences between four types of GG, 3'AG5', 3'GA5', and AA complexes, which are formed from four discrete DNA fragments recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments and high antitumour activity of ZD0473. The main reason for easier forming of 3'GA5' complex than the 3'AG5' one is that the drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the con-figuration transformation from such monoligand compound to the bi-ligand one is limited.

  1. Platinum impact assessment

    OpenAIRE

    Yip, Joyce Pui Yan

    2007-01-01

    This paper presents a comprehensive strategic analysis of Company X's strategies to mitigate its risks from volatile platinum prices, since Platinum is a critical component of fuel cells. It is recommended that Company X consider leasing platinum to lower cash flow requirements to meet its platinum demand over the next 5 years. A shorter platinum leasing period will reduce Company X's platinum market risk. OEMs can set up metal accounts with catalyst suppliers to eliminate Company X from plat...

  2. Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer

    Science.gov (United States)

    Wang, Li-Yang; Xie, Hua; Zhou, Hang; Yao, Wen-Xiu; Zhao, Xin; Wang, Yi

    2017-01-01

    Objectives: To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC). Methods: PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies. Results: A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p<0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95% CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting. Conclusion: The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients. PMID:28042625

  3. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  4. Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum, and survival.

    Science.gov (United States)

    Mukhopadhyay, Asima; Plummer, Elizabeth R; Elattar, Ahmed; Soohoo, San; Uzir, Bisha; Quinn, Jennifer E; McCluggage, W Glenn; Maxwell, Perry; Aneke, Harriet; Curtin, Nicola J; Edmondson, Richard J

    2012-11-15

    Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naïve patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome. ©2012 AACR.

  5. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    OpenAIRE

    Vyas, N; Turner, A; Sewell, G.

    2014-01-01

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an est...

  6. Membrane fuel cell cathode catalysts based on titanium oxide supported platinum nanoparticles.

    Science.gov (United States)

    Gebauer, Christian; Jusys, Zenonas; Wassner, Maximilian; Hüsing, Nicola; Behm, R Jürgen

    2014-07-21

    The potential of platinum catalysts supported on pure, nitrogen-, or carbon-doped titania for application in the oxygen reduction reaction (ORR), as a cathode catalyst in polymer electrolyte membrane fuel cells, is investigated. The oxide supports are synthesized by using a sol-gel route. Modification with nitrogen and carbon doping is achieved by thermal decomposition of urea and the structure-directing agent P123. Platinum nanoparticles are prepared by reduction of a Pt(IV) salt in ethylene glycol and subsequently immobilized on different support materials. Structural and electronic properties of the support materials and the resulting catalysts are characterized by various methods, including X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. These results and electrochemical characterization of the support materials and platinum nanoparticle catalysts indicate distinct support effects in the catalysts. The electrocatalytic performance of these catalysts in the ORR, as determined in rotating ring disc electrode measurements, is promising. Also here, distinct support effects can be identified. Correlations with the structural/electronic and the electrochemical properties are discussed, as well as the role of metal-support interactions.

  7. A multicenter study of recombinant human erythropoietin (epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy.

    Science.gov (United States)

    Pawlicki, M; Jassem, J; Bösze, P; Lotan, C; Kurteva, G P; Siddiqui, M; Kosmidis, P A; Rigatos, G A; Kansu, E; Durkovic, P; Aziz, Z; Al Idrissi, H; Roth, A; Cozma, G

    1997-11-01

    Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

  8. A risk-adapted strategy of radiotherapy or cisplatin-based chemotherapy in stage II seminoma.

    Science.gov (United States)

    Domont, Julien; Massard, Christophe; Patrikidou, Anna; Bossi, Alberto; de Crevoisier, Renaud; Rose, Mathieu; Wibault, Pierre; Fizazi, Karim

    2013-07-01

    Indications for radiotherapy and chemotherapy in stage II seminoma are currently debated. Since 1980, the policy at Institut Gustave Roussy was to treat patients with stage IIA-B disease with external radiotherapy and patients with stage IIB-C with cisplatin-based chemotherapy. In stage IIB disease, 3 cm was the usual tumor size threshold above which individual patients were considered for chemotherapy. During the period 1980-2001, 67 patients with stage II seminoma were treated: stage IIA (n = 5), stage IIB (n = 31), and stage IIC (n = 31). The median age was 40 years (range: 23-64). Among 37 patients who received radiotherapy, 5, 28, and 4 had a stage IIA, IIB, and IIC, respectively. Among 30 patients who received chemotherapy, 27 had a stage IIC. With a median follow-up of 9.4 years, 19 relapses (28%) occurred, including 11 and 8 cases treated with radiotherapy (30%) and chemotherapy (27%), respectively. The 5-year relapse-free survival was 71% (95% CI: 59-80). All but three relapses were salvaged with chemotherapy followed in selected cases by surgical resection of residual masses. Only 3 patients died of seminoma. The 5-year overall survival rate is 97% (95% CI: 89-99). Five patients subsequently developed a non-germ-cell second cancer, which occurred within the radiation field in 3 cases. With an overall survival rate of 97%, the overall outcome of patients with stage II seminoma managed according to this risk-adapted strategy is good. The possibility of extending the indications for chemotherapy to selected stage IIB seminoma patients needs to be further evaluated as potentially beneficial in terms of relapse risk. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Stability of Porous Platinum Nanoparticles: Combined In Situ TEM and Theoretical Study

    DEFF Research Database (Denmark)

    Chang, Shery L. Y.; Barnard, Amanda S.; Dwyer, Christian

    2012-01-01

    Porous platinum nanoparticles provide a route for the development of catalysts that use less platinum without sacrificing catalytic performance. Here, we examine porous platinum nanoparticles using a combination of in situ transmission electron microscopy and calculations based on a first...

  10. Efficacy and safety of ifosfamide-based chemotherapy for osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fan XL

    2015-11-01

    Full Text Available Xiao-Liang Fan,1,* Guo-Ping Cai,2,* Liu-Long Zhu,1 Guo-Ming Ding1 1Department of Orthopaedics, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, 2Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The efficacy of ifosfamide-based chemotherapy in the treatment of osteosarcoma has been investigated; however, results are inconsistent. Therefore, we reviewed the relevant studies and conducted a meta-analysis to assess the efficacy of ifosfamide-based chemotherapy in patients with osteosarcoma.Methods: A systematic literature search on PubMed, Embase, and Web of Science databases was performed. Eligible studies were clinical trials of patients with osteosarcoma who received ifosfamide-based chemotherapy. Hazard ratios (HRs were pooled to compare event-free survival (EFS and overall survival (OS. Risk ratios (RRs were pooled to compare good histologic response rates and adverse event incidence. Meta-analysis was performed using a fixed-effects model or a random-effects model according to heterogeneity.Results: A total of seven randomized controlled trials were included in this meta-analysis. Pooled results showed that ifosfamide-based chemotherapy significantly improved EFS (HR=0.72, 95% confidence interval [CI]: 0.63, 0.82; P=0.000 and OS (HR=0.83, 95% CI: 0.70, 0.99; P=0.034; furthermore, this form of chemotherapy increased good histologic response rate (RR=1.27, 95% CI: 1.10, 1.46; P=0.001. In addition, patients in the ifosfamide group exhibited a significantly higher incidence of fever (RR=2.23, 95% CI: 1.42, 3.50; P=0.000 and required more frequent platelet transfusion (RR=1.92, 95% CI: 1.23, 3.01; P=0.004.Conclusion: This meta-analysis confirmed that ifosfamide-based chemotherapy can significantly improve EFS and OS; this chemotherapy can also increase good histologic response rate in patients with osteosarcoma

  11. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2017-04-05

    Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Endometrial Undifferentiated Carcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Study of the catalytic layer in polybenzimidazole-based high temperature PEMFC: effect of platinum content on the carbon support

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, J.; Canizares, P.; Rodrigo, M.A.; Linares, J.J.; Ubeda, D.; Pinar, F.J. [Chemical Engineering Department, University of Castilla-La Mancha, Ciudad Real (Spain)

    2010-04-15

    In this work, the effect of platinum percentage on the carbon support of commercial catalyst for electrodes to be used in a Polybenzimidazole (PBI)-based PEMFC has been studied. Three percentages were studied (20, 40 and 60%). In all cases, the same quantity of PBI in the catalyst layer was added, which is required as a 'binder'. From Hg porosimetry analyses, pore size distribution, porosity, mean pore size and tortuosity of all electrodes were obtained. The amount of mesopores gets larger as the platinum percentage in the catalytic layer decreases, which reduces the overall porosity and the mean pore size and increases the tortuosity. The electrochemical characterisation was performed by voltamperometric studies, assessing the effective electrochemical surface area (ESA) of the electrodes, by impedance spectroscopy (IS), determining the polarisation resistance, and by the corresponding fuel cell measurements. The best results were obtained for the electrodes with a content of 40% Pt on carbon, as a result of an adequate combination of catalytic activity and mass transfer characteristics of the electrode. It has been demonstrated that the temperature favours the fuel cell performance, and the humidification does not have remarkable effects on the performance of a PBI-based polymer electrolyte membrane fuel cell (PEMFC). (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  13. A versatile quantitation platform based on platinum nanoparticles incorporated volumetric bar-chart chip for highly sensitive assays.

    Science.gov (United States)

    Wang, Yuzhen; Zhu, Guixian; Qi, Wenjin; Li, Ying; Song, Yujun

    2016-11-15

    Platinum nanoparticles incorporated volumetric bar-chart chip (PtNPs-V-Chip) is able to be used for point-of-care tests by providing quantitative and visualized readout without any assistance from instruments, data processing, or graphic plotting. To improve the sensitivity of PtNPs-V-Chip, hybridization chain reaction was employed in this quantitation platform for highly sensitive assays that can detect as low as 16 pM Ebola Virus DNA, 0.01ng/mL carcinoembryonic antigen (CEA), and the 10 HER2-expressing cancer cells. Based on this amplified strategy, a 100-fold decrease of detection limit was achieved for DNA by improving the number of platinum nanoparticle catalyst for the captured analyte. This quantitation platform can also distinguish single base mismatch of DNA hybridization and observe the concentration threshold of CEA. The new strategy lays the foundation for this quantitation platform to be applied in forensic analysis, biothreat detection, clinical diagnostics and drug screening.

  14. Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

    Directory of Open Access Journals (Sweden)

    Walsh Tom

    2009-07-01

    Full Text Available Abstract Background DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure. Results Of 115 primary sporadic ovarian carcinomas, 39 (34% had low BRCA1 protein and 49 (42% had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly concordant (p Conclusion Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.

  15. Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

    NARCIS (Netherlands)

    Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander|info:eu-repo/dai/nl/340300108; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

    2017-01-01

    Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

  16. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    Science.gov (United States)

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  17. Cisplatin-based chemotherapy changes the incidence of bilateral testicular cancer

    NARCIS (Netherlands)

    vanBasten, JPA; Hoekstra, HJ; vanDriel, MF; Sleijfer, DT; Droste, JHJ; Schraffordt Koops, H.

    1997-01-01

    Background: The introduction of cisplatin-based chemotherapy has remarkably increased the survival of testicular cancer patients. With this success, the concern for a contraIateral testicular tumor has increased. The aim of this study was to investigate whether the risk for contralateral testicular

  18. Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Summers, Yvonne; Daugaard, Gedske

    2017-01-01

    Purpose: The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy. Methods: This dose-finding, non-comparative study investigated the antiemetic effect and safety of ...

  19. Cisplatin-based chemotherapy changes the incidence of bilateral testicular cancer

    NARCIS (Netherlands)

    vanBasten, JPA; Hoekstra, HJ; vanDriel, MF; Sleijfer, DT; Droste, JHJ; Schraffordt Koops, H.

    1997-01-01

    Background: The introduction of cisplatin-based chemotherapy has remarkably increased the survival of testicular cancer patients. With this success, the concern for a contraIateral testicular tumor has increased. The aim of this study was to investigate whether the risk for contralateral testicular

  20. Panitumumab and pegylated liposomal doxorubicin to platinum-resistant epithelial ovarian cancer with KRAS wild-type: An ongoing, nonrandomized, multicenter, phase II trial

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Lund, B

    2010-01-01

    and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human...... of first or second line platinum-based chemotherapy. Only patients with maximum 2 prior lines of chemotherapy, measurable disease by CA125 criteria and with KRAS wild type are eligible. Patients are treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2 day 1, every 4 weeks. Tumor...... to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue...

  1. Relationship of methylation of MGMT gene regulated by platinum-contained regimens in plasma and efficacy of chemotherapy in diffuse large B cell lymphoma patients%含铂方案调节弥漫大B细胞淋巴瘤患者血浆MGMT基因甲基化及与化疗疗效关系

    Institute of Scientific and Technical Information of China (English)

    康马飞; 廖漓漓; 刘瑛; 骆梅青; 陈莹

    2012-01-01

    Objective:To detect the methylation of the 06 - methylguanine DNA methyltransferase( MGMT )gene in peripheral plasma in diffuse large B cell lymphoma( DLBCL )patients who treated with platinum - contained regimen and to evaluate whether platinum - contained regimen regulate methylation of MGMT gene and to evaluate the relationship of methylation of MGMT gene and efficacy of chemotherapy in diffuse large B cell lymphoma. Methods: Before and after chemotherapy, a nested methylation - specific PCR( nMSP )was performed for the detection of methylation of MGMT gene in plasma from DLBCL patients who treated with platinum - contained regimens. Results: Thirty plasma samples, before treatment with DHAP regimen, MGMT gene methylation was found in 10. 0% ( 3/30 )of patients with DLBCL which resisted to CHOP regimen. The ratios of methylation, after 2 and 4 cycls of chemotherapy, were respectively 63. 3%( 19/30 )and 73. 3%( 22/30 ) and there was a significant different between pre - therapy group and post - therapy group( P = 0. 000 ). The response rates were respectively 100% ( 3/3 )and 92. 6% ( 25/ 27 )in patients with methylation and non - methylation of MGMT gene after 2 cycles of platinum - contained regimens and were respectively 86. 4%( 19/22 )and 75.0%( 6/8 )after 4 cycles and there was no significant difference between methylation group and non - methylation group. Conclusion: Platinum - contained regimens might regulate methylation of MGMT gene. Efficacy of chemotherapy with platinum - contained regimens was not related with methylation of MGMT gene.%目的 检测弥漫大B细胞淋巴瘤(DLBCL)患者用含铂方案化疗后外周血血浆中O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)基因的甲基化状态,探讨含铂方案能否调节MGMT基因甲基化状态,并观察MGMT基因甲基化与含铂方案化疗疗效的关系.方法 利用巢式甲基化特异性聚合酶链反应法检测DLBCL患者含铂方案治疗前后

  2. The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast cancer patients receiving epirubicin and taxane based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Wenbin Zhou

    Full Text Available BACKGROUND: Chemotherapy-induced amenorrhea (CIA is common in young breast cancer patients. The incidence of CIA associated with regimens involving epirubicin and taxane was not well known. Furthermore, previous studies suggested leucopenia and amenorrhea may reflect inter-individual variations in pharmacokinetics. The purpose of this study was to investigate the association between leucopenia after first cycle of chemotherapy and CIA in young breast cancer patients receiving epirubicin and taxane based chemotherapy. Furthermore, the incidence of CIA was also assessed. METHODOLOGY AND PRINCIPAL FINDINGS: Between October 2008 and March 2010, 186 consecutive premenopausal patients, treated with epirubicin and taxane based chemotherapy, were recruited. Information about CIA was collected by telephone and out-patient clinic. Of these 186 patients, data from 165 patients were included and analyzed. Of all 165 patients, CIA occurred in 72 patients (43.64%. In multivariate analysis, age older than 40 y (OR: 16.10, 95% CI: 6.34-40.88, P0.05. The rate of CIA in leucopenia group (52.56% was significantly higher than that in normal leukocyte group (34.62% (P = 0.024. In patients treated with a FEC regimen (cyclophosphamide, epirubicin and 5-fluorouracil, the rate of CIA in leucopenia group (59.57% was significantly higher than that in normal leukocyte group (36.84% (P = 0.037. CONCLUSIONS: Age at diagnosis and previous childbearing were both found to significantly increase the risk of CIA, whereas additional taxane was not associated with increased rate of CIA. Importantly, leucopenia after first cycle of chemotherapy was associated with increased risk of CIA, which suggested that leucopenia may be an early predictor of chemotherapy-induced infertility.

  3. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  4. Catalytic wet-air oxidation of a chemical plant wastewater over platinum-based catalysts.

    Science.gov (United States)

    Cybulski, Andrzej; Trawczyński, Janusz

    2006-01-01

    Catalytic wet-air oxidation (CWAO) of wastewater (chemical oxygen demand [COD] = 1800 mg O2/dm3) from a fine chemicals plant was investigated in a fixed-bed reactor at T = 393-473 K under total pressure of 5.0 or 8.0 MPa. Catalysts containing 0.3% wt. of platinum deposited on two supports, mixed silica-titania (SM1) and carbon black composites (CBC) were used. The CBC-supported catalyst appeared to be more active than the SM1-supported one. A slow decrease of activity of the platinum on SM1 (Pt-SM1) during the long-term operation is attributed to recrystallization of titania and leaching of a support component, while the Pt-CBC catalyst is deteriorated, owing to combustion of the support component. The power-law-kinetic equations were used to describe the rate of COD removal at CWAO over the catalysts. The kinetic parameters of COD reduction for the wastewater were determined and compared with the kinetic parameters describing phenol oxidation over the same catalysts. Rates of COD removal for the wastewater were found higher than those for phenol oxidation over the same catalysts and under identical operating conditions.

  5. Nanoparticulate platinum films on gold using dendrimer-based wet chemical method

    Indian Academy of Sciences (India)

    S Raghu; Sheela Berchmans; K L N Phani; V Yegnaraman

    2005-11-01

    There is a growing interest in devising wet chemical alternatives for physical deposition methods for applications involving thin films, e.g., catalysis. Deposition of platinum on thin gold films is often a problem leading to incomplete coverage and improper adhesion to solid surfaces. Gold substrates often need pre-activation for achieving complete coverage. We demonstrate here that dendrimers with proper functionalities and size work as well-defined nucleating agents and adhesion promoters. This feature is demonstrated using an amine-terminated dendrimer of generation 4.0. This approach allows one to obtain adherent nanoparticulate films of platinum on gold. Unlike other nucleating agents and adhesion promoting compounds, dendrimers have a well-defined ordered structure in terms of their space filling ability. The stability of the films obtained with adsorbed dendrimers is emonstrated using the electrocatalytic reactions of fuels like methanol. The films formed without dendrimers cannot sustain the electro-oxidation currents due to the instability of the films while the films formed with dendrimers can sustain currents for longer duration and for several cycles. The dendrimer-derived Pt films exhibit higher catalytic activity compared to other methods.

  6. Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer.

    NARCIS (Netherlands)

    Timmer-Bonte, J.N.H.; Punt, C.J.A.; Heijden, H.F.M. van der; Die, C.E. van; Bussink, J.; Beijnen, J.H.; Huitema, A.D.; Tjan-Heijnen, V.C.

    2008-01-01

    In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a

  7. Cisplatin-based chemotherapy: Add high-frequency audiometry in the regimen

    Directory of Open Access Journals (Sweden)

    R Arora

    2009-01-01

    Full Text Available Background : Cisplatin-induced ototoxicity shows high interindividual variability and is often accompanied by transient or permanent tinnitus. It is not possible to identify the susceptible individuals before commencement of the treatment. We conducted a prospective, randomized and observational study in a tertiary care centre and evaluated the effects of different doses of cisplatin on hearing. Materials and Methods : Fifty-seven patients scheduled for cisplatin-based chemotherapy were included in the study. All patients were divided into three groups depending on the dose of cisplatin infused in 3 weeks. Results : The subjective hearing loss was found in seven patients, while six patients had tinnitus during the chemotherapy. The hearing loss was sensorineural, dose dependent, symmetrical, bilateral and irreversible. Higher frequencies were first to be affected in cisplatin chemotherapy. Conclusion : As use of high-frequency audiometry is still limited in research work only, we need a strict protocol of adding high-frequency audiometry in the cisplatin-based chemotherapy regimen.

  8. Comparison of different sample preparation methods for platinum determination in cultured cells by graphite furnace atomic absorption spectrometry

    Directory of Open Access Journals (Sweden)

    Man Xiao

    2017-01-01

    Full Text Available Background Platinum-based agents are widely used in chemotherapy against solid tumors and insufficient intracellular drug accumulation is one of the leading causes of platinum resistance which is associated with poor survival of tumor patients. Thus, the detection of intracellular platinum is pivotal for studies aiming to overcome platinum resistance. In the present study, we aimed to establish a reliable graphite furnace atomic absorption spectrometry (GFAAS-based assay to quantify the intracellular platinum content for cultured cells. Methods Several most commonly applied cell preparation methods, including 0.2% HNO3, 0.2% Triton X-100, concentrated nitric acid, RIPA combined with concentrated nitric acid and hydroxide, followed by GFAAS for platinum detection were compared in ovarian, cervical and liver cancer cell lines to obtain the optimal one, and parameters regarding linearity, accuracy, precision and sensitivity were evaluated. Influence of other metals on platinum detection and the storage conditions of samples were also determined. Results The treatment of cells with 0.2% HNO3 was superior to other approaches with fewer platinum loss and better repeatability. The recovery rate and precision of this method were 97.3%–103.0% and 1.4%–3.8%, respectively. The average recoveries in the presence of other metals were 95.1%–103.1%. The detection limit was 13.23 ug/L. The recovery rate of platinum remained acceptable even in cell samples stored in −20 °C or −80 °C for two months. Discussion After comparison, we found that 0.2% HNO3 was optimal for intracellular platinum quantification based on GFAAS, which presented values compatible with that of inductively-coupled plasma mass-spectrometry (ICP-MS, and this is partially attributed to the simplicity of this method. Moreover, the assay was proved to be accurate, sensitive, cost-effective and suitable for the research of platinum-based antitumor therapy.

  9. Long-term survivors of ovarian malignancies after cisplatin-based chemotherapy : cardiovascular risk factors and signs of vascular damage

    NARCIS (Netherlands)

    de Vos, FYFL; Nuver, J; Willemse, PHB; van der Zee, AGJ; Messerschraidt, J; Burgerhof, JGM; de Vries, EGE; Gietema, JA

    dMale germ cell tumour patients treated with cisplatin-based chemotherapy frequently develop cardiovascular risk factors and disease, but sparse information is available about long-term complications of this type of chemotherapy in women. We investigated the prevalence of cardiovascular risk factors

  10. Paclitaxel-Based Chemotherapy for Advanced Pancreatic Cancer after Gemcitabine-Based Therapy Failure: A Case Series of 5 Patients

    Directory of Open Access Journals (Sweden)

    Hisato Igarashi

    2011-11-01

    Full Text Available Background/Objectives: Gemcitabine (GEM is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. Results: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. Conclusion: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.

  11. Efficacy of Ginger in Control of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients Receiving Doxorubicin-Based Chemotherapy.

    Science.gov (United States)

    Ansari, Mansour; Porouhan, Pezhman; Mohammadianpanah, Mohammad; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar; Nasrollahi, Hamid; Hamedi, Seyed Hasan

    2016-01-01

    Nausea and vomiting are among the most serious side effects of chemotherapy, in some cases leading to treatment interruption or chemotherapy dose reduction. Ginger has long been known as an antiemetic drug, used for conditions such as motion sickness, nausea-vomiting in pregnancy, and post-operation side effects. One hundred and fifty female patients with breast cancer entered this prospective study and were randomized to receive ginger (500 mg ginger powder, twice a day for 3 days) or placebo. One hundred and nineteen patients completed the study: 57 of them received ginger and 62 received ginger for the frst 3 chemotherapy cycles. Mean age in all patients was 48.6 (25-79) years. After 1st chemotherapy, mean nausea in the ginger and control arms were 1.36 (±1.31) and 1.46 (±1.28) with no statistically significant difference. After the 2nd chemotherapy session, nausea score was slightly more in the ginger group (1.36 versus 1.32). After 3rd chemotherapy, mean nausea severity in control group was less than ginger group [1.37 (±1.14), versus 1.42 (±1.30)]. Considering all patients, nausea was slightly more severe in ginger arm. In ginger arm mean nausea score was 1.42 (±0.96) and in control arm it was 1.40 (±0.92). Mean vomiting scores after chemotherapy in ginger arm were 0.719 (±1.03), 0.68 (±1.00) and 0.77 (±1.18). In control arm, mean vomiting was 0.983 (±1.23), 1.03 (±1.22) and 1.15 (±1.27). In all sessions, ginger decreased vomiting severity from 1.4 (±1.04) to 0.71 (±0.86). None of the differences were significant. In those patients who received the AC regimen, vomiting was less severe (0.64±0.87) compared to those who received placebo (1.13±1.12), which was statistically significant (p-value <0.05). Further and larger studies are needed to draw conclusions.

  12. Platinum-induced ototoxicity: a review of prevailing ototoxicity criteria.

    Science.gov (United States)

    Waissbluth, Sofia; Peleva, Emilia; Daniel, Sam J

    2017-03-01

    The antineoplastic agent's cisplatin and carboplatin are widely used as they are highly effective. Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy. Clinically, patients generally develop a progressive, bilateral, and irreversible sensorineural hearing loss. With rising cancer survival rates, a greater proportion of patients are living with the side effects of their chemotherapy treatments. Consequently, the quality of life of cancer survivors has now become a major concern for clinicians. Various classification systems are currently available to grade side effects and provide a guideline for subsequent treatments. An extensive review of the literature revealed that a variety of criteria are used worldwide for grading platinum-induced hearing loss in children and adults, including the National Cancer Institute criteria, Brock's grading system, the American Speech-Hearing-Language Association criteria, the World Health Organization criteria, the Pediatric Oncology Group criteria, and the Muenster classification. Less commonly used criteria include the Chang classification, the Functional Hearing Loss scale, the HIT system (German Hirntumor study grading system), and most recently, the International Society of Pediatric Oncology Boston ototoxicity grading scale. The objective of this review is to evaluate the commonly used ototoxicity criteria and discuss their benefits and limitations.

  13. Optimising the treatment of the partially platinum-sensitive relapsed ovarian cancer patient

    Directory of Open Access Journals (Sweden)

    Nicoletta Colombo

    2014-12-01

    Full Text Available The choice of second-line chemotherapy in patients with recurrent ovarian cancer (ROC is complex, with several factors to be considered, the most important of which is the length of the platinum-free treatment interval (PFI. Recently ROC patients have been further stratified into platinum sensitive (PS, partially platinum sensitive (PPS and platinum resistant (PR subgroups depending on the length of the PFI. Response to second-line therapy, progression-free survival (PFS and overall survival (OS are linked to the PFI, all of them improving as the PFI increases. Consequently, there is increasing interest in PFI extension strategies with platinum-free therapeutic options. Such strategies are currently being studied in patients with partially platinum-sensitive disease (PFI 6-12 months, as the treatment of these patients remains clinically challenging. A non-platinum option, trabectedin + pegylated liposomal doxorubicin (PLD combination, has been evaluated in ROC patients in the pivotal phase III OVA-301 study. The OVA-301 study differed from previous trials in the same setting as it included only patients who were not expected to benefit from or who were ineligible for or who were unwilling to receive re-treatment with platinum-based chemotherapy, including those with PPS and PR disease. Subset analysis of patients with PPS disease in OVA-301 showed that the trabectedin + PLD combination significantly improved PFS compared with PLD alone; median PFS 7.4 versus 5.5 months, p=0.0152. Final survival data from the same subset of patients, showed that trabectedin + PLD also achieved a significant 36% decrease in the risk of death compared with PLD alone (HR=0.64; 95% CI, 0.47–0.88; p=0.0027. Median overall survival (OS was 22.4 months in the trabectedin + PLD arm versus 16.4 months in the PLD arm. This represents a statistically significant 6-month improvement in median OS in patients treated with trabectedin + PLD compared to those treated with PLD

  14. Three-dimensional ordered macroporous platinum-based electrode for methanol oxidation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In this paper, three-dimensional ordered macroporous platinum catalysts with high real surface area were synthesized using the inverted colloidal crystals template technique and have been employed for the electrooxidation of methanol. The morphology and electrocatalytic behavior of the porous Pt electrodes were investigated with atomic force microscopy and electrochemical techniques. For the same amount of Pt deposited, the real surface areas of the electrodes are 9.16 and 8.00 cm2 for the porous electrodes with pore size of 320 and 500 nm respectively, which are more than 5 times larger than the directly deposited Pt electrode (1.4 cm2). The pore size effect on the methanol electrooxidation was investigated by testing low concentration solution of methanol and porous materials with different pore sizes. The synthesized macroporous Pt electrode shows high stability toward the electrooxidation of methanol and is promising for the direct methanol fuel cell.

  15. Voltammetric Determination of Salbutamol Based on Electrochemical Oxidation at Platinum and Glassy Carbon Electrodes

    OpenAIRE

    YILMAZ, Niyazi; Sibel A. Özkan; USLU, Bengi

    1998-01-01

    The oxidative behavior of salbutamol was studied as a function of pH at platinum and activated glassy carbon electrodes. Between pH 1.9 and 12.0, the drug was characterized by a single oxidation step at both electrodes. The process was found to be dependent on the nature and the pH of the supporting elctrolyte. The procedure yielded a linear concentration range of 1 \\times 10-4 to 1 \\times 10-3 M and 2 \\times 10-5 to 1 \\times 10-3 M in 0.2 M sulphuric acid and a phosphate buffer of pH 6, at p...

  16. Amperometric Determination of Indole-3-acetic Acid Based on Platinum Nanowires and Carbon Nanotubes

    Institute of Scientific and Technical Information of China (English)

    Ruo Zhong WANG; Lang Tao XIAO; Ming Hui YANG; Jun Hui DING; Feng Li QU; Guo Li SHEN

    2006-01-01

    Platinum nanowire (PtNW) can be grown by electrodeposition in polycarbonate membrane, with the average diameter of the nanowires about 250 nm. The PtNW and multiwalled carbon nanotubes (CNT) are then dispersed into chitosan (CHIT) solution. The resulting PtNW-CNT-CHIT material brings new capabilities for electrochemical devices by using the synergistic action of the electrocatalytic activity of PtNW and CNT. By dropping the PtNW-CNT-CHIT film onto the glassy carbon (GC) electrode surface, and after evaporationan amperometric sensor for the determination of indole-3-acetic acid (IAA) was developed. The oxidation current of IAA increased significantly at the PtNW-CNT-CHIT film coated GC electrode,in contrast to that at the CNT-CHIT modified GC. The linear response of the sensor is from 50ng/ml to 50 μg/ml with a detection limit of 25 ng/mL.

  17. EXAFS structural study of platinum-based anticancer drugs degradation in presence of sulfur nucleophilic species.

    Science.gov (United States)

    Provost, Karine; Bouvet-Muller, Diane; Crauste-Manciet, Sylvie; Moscovici, Jacques; Olivi, Luca; Vlaic, Gilberto; Michalowicz, Alain

    2009-10-01

    Three platinum complexes, cisplatin, carboplatin and oxaliplatin are currently used worldwide. Investigation of their main structural modifications in presence of sulfur nucleophiles is of particular interest because of the implication of thiol and thioether groups in biochemical mechanism of action, resistance mechanism and in vivo or in vitro detoxification. We present the main structural results we have obtained concerning the reaction of these drugs with diverse sulfur nucleophiles (cysteine, glutathione, methionine, thiosulfate and thiocyanate), monitored in solution or as precipitates by EXAFS spectroscopy. The reactivities of the carboxylate and amine ligands of both carboplatin and oxaliplatin are compared, on the basis of first-coordination sphere modeling. Among the new results of this EXAFS study, we present the first observation of oxaliplatin diaminocyclohexane ligand displacement by sulfur nucleophiles.

  18. Platinum-based nanocomposite electrodes for low-temperature solid oxide fuel cells with extended lifetime

    Science.gov (United States)

    Lee, Yoon Ho; Cho, Gu Young; Chang, Ikwhang; Ji, Sanghoon; Kim, Young Beom; Cha, Suk Won

    2016-03-01

    Due to its high catalytic activity and convenient fabrication procedure that uses physical vapor deposition (PVD), nanofabricated platinum (Pt) is widely used for low temperature operating solid oxide fuel cells (LT-SOFC). However, the poor thermal stability of nanofabricated Pt accelerates cell performance degradation. To solve this problem, we apply a thermal barrier coating and use the dispersion hardening process for the nanofabrication of Pt by sputter device. Through morphological and electrochemical data, GDC modified nano-porous Pt electrodes shows improved performance and thermal stability at the operating temperature of 500 °C. While the peak power density of pure Pt sample is 6.16 mW cm-2 with a performance degradation of 43% in an hour, the peak power density of the GDC modified Pt electrodes are in range of 7.42-7.91 mW cm-2 with a 7-16% of performance degradation.

  19. SEM method for direct visual tracking of nanoscale morphological changes of platinum based electrocatalysts on fixed locations upon electrochemical or thermal treatments.

    Science.gov (United States)

    Zorko, Milena; Jozinović, Barbara; Bele, Marjan; Hodnik, Nejc; Gaberšček, Miran

    2014-05-01

    A general method for tracking morphological surface changes on a nanometer scale with scanning electron microscopy (SEM) is introduced. We exemplify the usefulness of the method by showing consecutive SEM images of an identical location before and after the electrochemical and thermal treatments of platinum-based nanoparticles deposited on a high surface area carbon. Observations reveal an insight into platinum based catalyst degradation occurring during potential cycling treatment. The presence of chloride clearly increases the rate of degradation. At these conditions the dominant degradation mechanism seems to be the platinum dissolution with some subsequent redeposition on the top of the catalyst film. By contrast, at the temperature of 60°C, under potentiostatic conditions some carbon corrosion and particle aggregation was observed. Temperature treatment simulating the annealing step of the synthesis reveals sintering of small platinum based composite aggregates into uniform spherical particles. The method provides a direct proof of induced surface phenomena occurring on a chosen location without the usual statistical uncertainty in usual, random SEM observations across relatively large surface areas.

  20. A first principles study of pristine and Al-doped boron nitride nanotubes interacting with platinum-based anticancer drugs

    Science.gov (United States)

    Shakerzadeh, Ehsan; Noorizadeh, Siamak

    2014-03-01

    Interaction of cis-platin and neda-platin, two conventional platinum-based anticancer drugs, with pristine [8,8] and Al-doped [8,0] boron nitride nanotubes (BNNTs) are investigated using the density functional theory (DFT) method. The obtained results indicate that cis-platin and neda-platin weakly interact with pristine zig zag or armchair BNNTs with a little dependency on the adsorbing positions; while both cis-platin and neda-platin are preferentially adsorbed onto the Al atom of the Al-doped BNNT with considerable adsorption energies. Therefore the Al-doped-BNNT might be an efficient carrier for delivery of these drugs in nanomedicine domain. The electronic structures of the stable configurations are also investigated through both DOS and PDOS spectra. The obtained results introduce the Al-doped-BNNT as an efficient carrier for delivery of cis-platin and neda-platin in nanomedicine domain.

  1. Preparation and Biological Evaluation of Two Novel Platinum(II Complexes Based on the Ligands of Dipicolyamine Bisphosphonate Esters

    Directory of Open Access Journals (Sweden)

    Ling Qiu

    2016-02-01

    Full Text Available Two new platinum(II-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA, which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2 were evaluated and compared with cisplatin (CDDP. Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP.

  2. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    Science.gov (United States)

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-05-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  3. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors.

    Science.gov (United States)

    Wei, Yuming; Poon, Daniel C; Fei, Rong; Lam, Amy S M; Au-Yeung, Steve C F; To, Kenneth K W

    2016-05-06

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  4. Port central venous catheters-associated bloodstream infection during outpatient-based chemotherapy.

    Science.gov (United States)

    Mauri, Davide; Roumbkou, Sofia; Michalopoulou, Stella; Tsali, Lamprini; Spiliopoulou, Anastasia; Panou, Charalampos; Valachis, Antonis; Panagopoulos, Angelos; Polyzos, Nikolaos P

    2010-12-01

    Central venous catheters (CVCs) are commonly used for the administration of intravenous chemotherapy in outpatient setting. Nevertheless, outbreaks of catheter-associated bloodstream infections had been reported from oncology centers. We describe a large outbreak of CVCs-associated Klebsiella oxytoca bloodstream infection, occurring in an oncology chemotherapy outpatient unit of northern Greece between October 2006 and May 2007. The outbreak involved approximately 10% of the patients with CVCs who were receiving home-based chemotherapy, and it represents the second larger outbreak of CVCs-associated BSIs due to Klebsiella oxytoca in oncology outpatient centers. We retrospectively analyzed the chain of investigations and prophylactic/diagnostic measures taken to eradicate the infection: (1) patients' chart audit, (2) estimation of the infection among asymptomatic patients, (3) implementation of the level of awareness of medical and paramedical personnel, (4) collection of samples from environment, medications and infusion materials, (5) critical appraisal of chemotherapeutical schemes and (6) cooperation with peripheral institutions. The isolation of Klebsiella oxytoca in a chemotherapy solution (infusional 5-FU in dextrose 5% solution within a 48 h pump) from a peripheral General Hospital and the prompt transmission of the data to the chemotherapy center played a key role for the management of the infection cluster. This is the first report that evidenced the detection of Klebsiella oxytoca within a chemotherapeutical preparation. Data transmission from peripheral hospitals to the central institution resulted in an important feedback that allowed a better estimation of the infection cluster and more tailored actions for the eradication of the infection.

  5. Trabectedin therapy as an emerging treatment strategy for recurrent platinum-sensitive ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Jos Antonio Lpez-Guerrero; Ignacio Romero; Andrs Poveda

    2015-01-01

    Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking folowed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients wil develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the celular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.

  6. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Suk [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Guo, Chunlu; Thompson, Eric L. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Jiang, Yanlin [Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Lee, Suk-Hee, E-mail: slee@iu.edu [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States)

    2015-09-15

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.

  7. Radiotherapy alone or combined with chemotherapy for base of tongue squamous cell carcinoma.

    Science.gov (United States)

    Christopherson, Kaitlin; Morris, Christopher G; Kirwan, Jessica M; Amdur, Robert J; Dziegielewski, Peter T; Boyce, Brian J; Mendenhall, William M

    2017-07-01

    To evaluate the long-term disease control, survival, and complications after definitive radiotherapy (RT) alone or combined with adjuvant chemotherapy with or without planned neck dissection for base of tongue squamous cell carcinoma (SCC). We retrospectively reviewed the medical records of 467 patients treated at the University of Florida with definitive RT alone or combined with adjuvant chemotherapy between 1964 and 2011 for base of tongue SCC. Median follow-up was 5.6 years. Median total dose to the primary site was 74.4 Gy. Eighty-seven patients (19%) were treated with once-daily fractionation, and 380 (81%) received altered fractionation schedules. Intensity-modulated RT was used in 128 patients (27%). Chemotherapy was administered to 173 (37%) patients. Planned neck dissection after RT was performed in 226 patients (48%). Data regarding p16 pathway activation were available for 25 patients. At 5 years, the local, local-regional, and regional control rates were 85.5%, 80.0%, and 90.0%, respectively. The 5-year overall, cause-specific, and distant metastasis-free survival rates were 59.1%, 71.5%, and 84.1%, respectively. Sixty-four patients (14%) developed one or more severe late complications. Fifty patients (11%) required late gastrostomy tube placement. This study supports the continued use of RT alone or combined with adjuvant chemotherapy for patients with base of tongue SCC, as this treatment yields high rates of cause-specific survival and disease control, with a relatively low rate of late complications. 4. Laryngoscope, 127:1589-1594, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome.

    Science.gov (United States)

    Jastaniah, Wasil

    2017-07-01

    This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment. © 2016 Wiley Periodicals, Inc.

  9. Impact of Diabetes Mellitus on the Treatment Outcomes of Chemotherapy in Women with Breast Cancer-A Population-Based Prospective Cohort Study

    Institute of Scientific and Technical Information of China (English)

    Yu-Ching Chen; Cheng-Wei Chang; Jorng-Tzong Horng; Yan-Jun Chen; Jin-Tsung Yang

    2015-01-01

    Abstract¾There are few population-based data in investigating the impact of diabetes on chemotherapy adverse effects and treatment outcomes of non-metastatic breast cancer. The purpose of this study is to evaluate whether diabetes affects the patterns of use in chemotherapy, toxic effects of chemotherapy, and treatment outcomes for non-metastatic breast cancer in Taiwan. The study results can provide physicians for making a decision whether or not to use chemotherapy based on the individual patients’ condition.

  10. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  11. Platinum plasmonic nanostructure arrays for massively parallel single-molecule detection based on enhanced fluorescence measurements.

    Science.gov (United States)

    Saito, Toshiro; Takahashi, Satoshi; Obara, Takayuki; Itabashi, Naoshi; Imai, Kazumichi

    2011-11-04

    We fabricated platinum bowtie nanostructure arrays producing fluorescence enhancement and evaluated their performance using two-photon photoluminescence and single-molecule fluorescence measurements. A comprehensive selection of suitable materials was explored by electromagnetic simulation and Pt was chosen as the plasmonic material for visible light excitation near 500 nm, which is preferable for multicolor dye-labeling applications like DNA sequencing. The observation of bright photoluminescence (λ = 500-600 nm) from each Pt nanostructure, induced by irradiation at 800 nm with a femtosecond laser pulse, clearly indicates that a highly enhanced local field is created near the Pt nanostructure. The attachment of a single dye molecule was attempted between the Pt triangles of each nanostructure by using selective immobilization chemistry. The fluorescence intensities of the single dye molecule localized on the nanostructures were measured. A highly enhanced fluorescence, which was increased by a factor of 30, was observed. The two-photon photoluminescence intensity and fluorescence intensity showed qualitatively consistent gap size dependence. However, the average fluorescence enhancement factor was rather repressed even in the nanostructure with the smallest gap size compared to the large growth of photoluminescence. The variation of the position of the dye molecule attached to the nanostructure may influence the wide distribution of the fluorescence enhancement factor and cause the rather small average value of the fluorescence enhancement factor.

  12. The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo

    Directory of Open Access Journals (Sweden)

    Bouchal Pavel

    2011-10-01

    Full Text Available Abstract Background The initial pharmacokinetic study of a new anticancer agent (OC-6-43-bis(acetato(1-adamantylamineamminedichloroplatinum (IV (LA-12 was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring. Methods Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. Results We identified Retinol-binding protein 4 (RBP4 whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials. Conclusions RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.

  13. Ovarian cancer stem cell like side populations are enriched following chemotherapy and overexpress EZH2

    Science.gov (United States)

    Rizzo, Siân; Hersey, Jenny M.; Mellor, Paul; Dai, Wei; Santos-Silva, Alessandra; Liber, Daniel; Luk, Louisa; Titley, Ian; Carden, Craig P; Box, Garry; Hudson, David L.; Kaye, Stanley B.; Brown, Robert

    2010-01-01

    Platinum-based chemotherapy, with cytoreductive surgery, is the cornerstone of treatment of advanced ovarian cancer, however acquired drug resistance is a major clinical obstacle. It has been proposed that subpopulations of tumour cells with stem-cell like properties, such as so-called side populations (SP) which over-express ABC drug-transporters, can sustain the growth of drug resistant tumour cells, leading to tumour recurrence following chemotherapy. The histone methyltransferase EZH2 is a key component of the Polycomb Repressive Complex 2 (PRC2) required for maintenance of a stem cell state and overexpression has been implicated in drug resistance and shorter survival of ovarian cancer patients. We observe higher percentage SP in ascites from patients that have relapsed following chemotherapy compared to chemonaive patients, consistent with selection for this subpopulation during platinum-based chemotherapy. Furthermore, ABCB1 (P-glycoprotein) and EZH2 are consistently over-expressed in SP compared to non-SP from patients’ tumour cells. SiRNA knockdown of EZH2 leads to loss of SP in ovarian tumour models, reduced anchorage-independent growth and reduced tumour growth in vivo. Together these data support a key role for EZH2 in the maintenance of a drug-resistant tumour-sustaining subpopulation of cells in ovarian cancers undergoing chemotherapy. As such, EZH2 is an important target for anticancer drug development. PMID:21216927

  14. PLATINUM AND FUEL CELLS

    Science.gov (United States)

    Platinum requirements for fuel cell vehicles (FCVS) have been identified as a concern and possible problem with FCV market penetration. Platinum is a necessary component of the electrodes of fuel cell engines that power the vehicles. The platinum is deposited on porous electrodes...

  15. Understanding Chemotherapy

    Science.gov (United States)

    N ational C ancer I nstitute Understanding Chemotherapy What is chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It is also called “chemo.” Today, there are ...

  16. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

    Directory of Open Access Journals (Sweden)

    Alletti Desiderio

    2008-09-01

    Full Text Available Abstract Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056 and less advanced FIGO stage (p = 0.025. At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024. About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03. Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026, with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04. Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023. Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

  17. [Platinum compounds: metabolism, toxicity and supportive strategies].

    Science.gov (United States)

    Lipp, H P; Hartmann, J T

    2005-02-09

    Although the leading platinum compounds, cisplatin, carboplatin, and oxaliplatin, share some structural similarities, there are marked differences between them in therapeutic uses, pharmacokinetics, and adverse effects profiles. Compared with cisplatin, carboplatin has inferior efficacy in germ-cell tumors, head and neck cancers, and bladder and esophageal carcinomas, whereas the two drugs appear to have comparable efficacy in ovarian cancer, extensive small-cell lung cancers (SCLC), and advanced non-small-cell lung cancers (NSCLC). Oxaliplatin belongs to the group of diaminocyclohexane (DACH) platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid. Nedaplatin has been registered in Japan, whereas other derivatives, like JM216 (which is the only orally available platinum derivative), ZD0473, BBR3464, and SPI-77 (a liposomal formulation of cisplatin), are still under investigation. The adverse effects of platinum compounds are reviewed together with possible prevention strategies.

  18. Design and Electrochemical Study of Platinum-Based Nanomaterials for Sensitive Detection of Nitric Oxide in Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Maduraiveeran Govindhan

    2016-11-01

    Full Text Available The extensive physiological and regulatory roles of nitric oxide (NO have spurred the development of NO sensors, which are of critical importance in neuroscience and various medical applications. The development of electrochemical NO sensors is of significant importance, and has garnered a tremendous amount of attention due to their high sensitivity and selectivity, rapid response, low cost, miniaturization, and the possibility of real-time monitoring. Nanostructured platinum (Pt-based materials have attracted considerable interest regarding their use in the design of electrochemical sensors for the detection of NO, due to their unique properties and the potential for new and innovative applications. This review focuses primarily on advances and insights into the utilization of nanostructured Pt-based electrode materials, such as nanoporous Pt, Pt and PtAu nanoparticles, PtAu nanoparticle/reduced graphene oxide (rGO, and PtW nanoparticle/rGO-ionic liquid (IL nanocomposites, for the detection of NO. The design, fabrication, characterization, and integration of electrochemical NO sensing performance, selectivity, and durability are addressed. The attractive electrochemical properties of Pt-based nanomaterials have great potential for increasing the competitiveness of these new sensors and open up new opportunities in the creation of novel NO-sensing technologies for biological and medical applications.

  19. Elaboration, physical and electrochemical characterizations of CO tolerant PEMFC anode materials. Study of platinum-molybdenum and platinum-tungsten alloys and composites; Elaborations et caracterisations electrochimiques et physiques de materiaux d'anode de PEMFC peu sensibles a l'empoisonnement par CO: etude d'alliages et de composites a base de platine-molybdene et de platine-tungstene

    Energy Technology Data Exchange (ETDEWEB)

    Peyrelade, E.

    2005-06-15

    PEMFC development is hindered by the CO poisoning ability of the anode platinum catalyst. It has been previously shown that the oxidation potential of carbon monoxide adsorbed on the platinum atoms can be lowered using specific Pt based catalysts, either metallic alloys or composites. The objective is then to realize a catalyst for which the CO oxidation is compatible with the working potential of a PEMFC anode. In our approach, to enhance the CO tolerance of platinum based catalyst supported on carbon, we studied platinum-tungsten and platinum-molybdenum alloys and platinum-metal oxide materials (Pt-WO{sub x} and Pt-MoO{sub x}). The platinum based alloys demonstrate a small effect of the second metal towards the oxidation of carbon monoxide. The platinum composites show a better tolerance to carbon monoxide. Electrochemical studies on both Pt-MoO{sub x} and Pt-WO{sub x} demonstrate the ability of the metal-oxides to promote the ability of Pt to oxidize CO at low potentials. However, chrono-amperometric tests reveal a bigger influence of the tungsten oxide. Complex chemistry reactions on the molybdenum oxide surface make it more difficult to observe. (author)

  20. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy

    OpenAIRE

    Huang, Xuan-zhang; Gao, Peng; Song, Yong-xi; Sun, Jing-xu; Chen, Xiao-wan; Zhao, Jun-hua; Ma, Bin; Wang, Jun; Wang, Zhen-ning

    2016-01-01

    Background Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992–2009. We enrolled patients with yp sta...

  1. The Role of Evidence Based Nursing in Prevention of Gastrointestinal Side Effects of Chemotherapy in Children with Cancer

    Directory of Open Access Journals (Sweden)

    Z Pouresmail

    2014-04-01

    Full Text Available Introduction: Today, due to the broad spectrum of pediatric cancers are treated by the chemotherapy drugs, but these drugs have side effects and gastrointestinal toxicity is the most prevalent. One of the main roles of nurses is to better health through patient education and care for him. Evidence-based nursing is a process during which the nurse can use the available research evidence, their clinical expertise and the patient has to take appropriate decisions. This study reviews the role of evidence-based nursing in the prevention of gastrointestinal side effects of chemotherapy in children with cancer was conducted.   Materials and Methods: Seeking information was performing through databases PubMed, SID, Since Direct, magiran, Ovid and etc. Within the years 2014-2002, the key issues in terms of evidence-based nursing, gastrointestinal side effect, chemotherapy was performed and 20 were studied English equivalents.   Results: The most common gastrointestinal side effects in children undergoing chemotherapy are oral ulcers, vomiting, diarrhea, and dysphagia. Different strategies for prevention studies suggest that these effects need to perform their roles in teaching and nursing care. Nurses can use the results of studies such as music, ginger, semi sitting positions during chemotherapy, use of ice and etc. To prevent vomiting, the use of  Persica for oral wound healing, hygiene perform especially hand washing for preventing diarrhea. The most important roles of nursing are recommended, Education on prevention of chemotherapy complications, adverse effects of proper nutrition and etc.   Conclusion: Nurses can play an effective role in the education and care to relieve symptoms and prevent progression of gastrointestinal side effects of chemotherapy.   Key words: Evidence-based nursing, Gastrointestinal side effects, Chemotherapy, Cancer  

  2. Decreased dose density of standard chemotherapy does not compromise survival for ovarian cancer patients.

    Science.gov (United States)

    Molckovsky, A; Vijay, S M; Hopman, W M; Bryson, P; Jeffrey, J F; Biagi, J J

    2008-01-01

    For women diagnosed with ovarian cancer, the standard practice of surgery followed by adjuvant platinum-taxane combination chemotherapy, with cycles administered every 3 weeks, is based on randomized control trials. However, a substantial number of patients require delays or reductions on this schedule. The Cancer Centre of Southeastern Ontario (CCSEO) has historically administered chemotherapy every 4 weeks. We analyzed survival outcomes of our cohort. All ovarian cancer patients treated with chemotherapy at the CCSEO from 1995 to end-2002 were included in this study. Overall survival and progression-free survival were calculated from initiation of chemotherapy using the Kaplan-Meier technique and log-rank tests. Cox regression analysis was used to adjust for age and disease stage. A total of 171 patients were treated with chemotherapy (cisplatin-paclitaxel or carboplatin-paclitaxel), of which 144 received chemotherapy every 4 weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for the group treated every 4 weeks vs 13.2 months for the 3-weekly group. Median overall survival was 36.5 months compared to 27.1 months, respectively. Trends favored treatment every 4 weeks. In early-stage disease, 5-year overall survival was 74% and 5-year progression-free survival was 68%. Administration of platinum-paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer patients. Importantly, median survival is favorable compared to results from landmark trials where patients were treated every 3 weeks. These results suggest that decreasing the frequency of chemotherapy cycles does not decrease survival. Prospective trials would be required to compare quality of life and cost-effectiveness.

  3. Electrochemical Analysis of the Electrodeposition of Platinum Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-Min; Cho, Sung-Woon; Kim, Jun-Hyun; Kim, Chang-Koo [Ajou University, Suwon (Korea, Republic of)

    2015-10-15

    A bath for electrodeposition of platinum nanoparticles on low-cost graphite substrates was developed to attach nanoparticles directly onto a substrate, and electrochemical characteristics of the electrodeposition of platinum nanoparticles were investigated. The reaction mechanism was examined by the analysis of polarization behavior. Cyclic voltammetry measurements revealed that the electrodeposition of platinum nanoparticles was limited by mass transfer. The chronoamperometric study showed an instantaneous nucleation mechanism during the electrodeposition of platinum nanoparticles on graphite. Because graphite is much cheaper than other carbon-based substrates, the electrodeposition of platinum nanoparticles on the graphite is expected to have useful applications.

  4. SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

    Science.gov (United States)

    Shi, Mingguang; He, Jianmin

    2016-04-01

    Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

  5. Phase II studies of dianhydrogalactitol-based combination chemotherapy for recurrent brain tumors.

    Science.gov (United States)

    Eagan, R T; Creagan, E T; Bisel, H F; Layton, D D; Groover, R V; Herman, R C

    1981-01-01

    The drug combinations of dianhydrogalactitol and VP-16 and dianhydrogalactitol, VP-16, and triazinate were used in patients with primary brain tumors, principally astrocytoma, recurrent following cranial irradiation. Tumor regressions were noted in 40% of patients treated with the 2-drug regimen and in 33% of patients treated with the 3-drug regimens. Regression were noted in all grades of tumor. Poor performance score on the patients' part did not seem to effect regression rates. Myelosuppression was the principal toxicity encountered. Dianhydrogalactitol-based combination chemotherapy seems as active as nitrosourea therapy and presents an alternative to nitrosourea therapy.

  6. DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex.

    Science.gov (United States)

    McGinely, Nicola L; Plumb, Jane A; Wheate, Nial J

    2013-11-01

    The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10(4) M(-1). Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.

  7. Direct ethanol fuel cell (DEFC): Electrical performances and reaction products distribution under operating conditions with different platinum-based anodes

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, S.; Coutanceau, C.; Lamy, C.; Leger, J.-M. [Laboratoire de Catalyse en Chimie Organique, -Equipe Electrocatalyse- UMR-CNRS 6503, Universite de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex (France)

    2006-07-14

    Ethanol electro-oxidation at different Pt-based electrodes was investigated in a single direct ethanol fuel cell (DEFC) in terms of reaction product distribution depending on the anode catalyst. In DEFC experiments, only three reaction products were detected using HPLC: acetaldehyde (AAL), acetic acid (AA) and CO{sub 2}. The addition of tin to platinum increases the activity of the catalyst by several order of magnitude and the electrical performance of the DEFC are greatly enhanced from a few mWcm{sup -2} to 30mWcm{sup -2} at 80{sup o}C, with Pt/C and Pt-Sn/C catalysts, respectively. Moreover, at Pt-Sn/C and Pt-Sn-Ru/C the formation of CO{sub 2} and AAL is lowered whereas the formation of AA is increased in comparison to what happens at a Pt/C catalyst. The addition of Ru to Pt-Sn only leads to enhance the electrical performance of the DEFC, i.e. the activity of the catalyst, but does not modify the product distribution. Very good stability in the open circuit voltage of the DEFC (close to 0.75V) was observed over a period of 2 weeks at 90{sup o}C, the cell undergoing start-run-stop cycles each day. Good stability under operating conditions at a given current density was also observed over 6h. (author)

  8. Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo

    Directory of Open Access Journals (Sweden)

    Nigel T. Maidment

    2008-08-01

    Full Text Available Using Micro-Electro-Mechanical-Systems (MEMS technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs modified with glutamate oxidase (GluOx for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1μM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

  9. Helium-based cold atmospheric plasma-induced reactive oxygen species-mediated apoptotic pathway attenuated by platinum nanoparticles.

    Science.gov (United States)

    Jawaid, Paras; Rehman, Mati Ur; Zhao, Qing Li; Takeda, Keigo; Ishikawa, Kenji; Hori, Masaru; Shimizu, Tadamichi; Kondo, Takashi

    2016-09-01

    Plasma is generated by ionizing gas molecules. Helium (He)-based cold atmospheric plasma (CAP) was generated using a high-voltage power supply with low-frequency excitation (60 Hz at 7 kV) and He flow at 2 l/min. Platinum nanoparticles (Pt-NPs) are potent antioxidants due to their unique ability to scavenge superoxides and peroxides. These features make them useful for the protection against oxidative stress-associated pathologies. Here, the effects of Pt-NPs on He-CAP-induced apoptosis and the underlying mechanism were examined in human lymphoma U937 cells. Apoptosis was measured after cells were exposed to He-CAP in the presence or absence of Pt-NPs. The effects of combined treatment were determined by observing the changes in intracellular reactive oxygen species (ROS) and both mitochondrial and Fas dependent pathway. The results indicate that Pt-NPs substantially scavenge He-CAP-induced superoxides and peroxides and inhibit all the pathways involved in apoptosis execution. This might be because of the SOD/catalase mimetic effects of Pt-NPs. These results showed that the Pt-NPs can induce He-CAP desensitization in human lymphoma U937 cells.

  10. Chromosome 17 centromere duplication and responsiveness to anthracycline-based neoadjuvant chemotherapy in breast cancer.

    Science.gov (United States)

    Tibau, Ariadna; López-Vilaró, Laura; Pérez-Olabarria, Maitane; Vázquez, Tania; Pons, Cristina; Gich, Ignasi; Alonso, Carmen; Ojeda, Belén; Ramón y Cajal, Teresa; Lerma, Enrique; Barnadas, Agustí; Escuin, Daniel

    2014-10-01

    Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.

  11. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  12. Anticancer platinum (IV) prodrugs with novel modes of activity.

    Science.gov (United States)

    Chin, Chee Fei; Wong, Daniel Yuan Qiang; Jothibasu, Ramasamy; Ang, Wee Han

    2011-01-01

    Over the past four decades, the search for improved platinum drugs based on the classical platinum (II)-diam(m)ine pharmacophore has yielded only a handful of successful candidates. New methodologies centred on platinum (IV) complexes, with better stability and expanded coordination spheres, offer the possibility of overcoming limitations inherent to platinum (II) drugs. In this review, novel strategies of targeting and killing cancer cells using platinum (IV) constructs are discussed. These approaches exploit the unique electrochemical characteristics and structural attributes of platinum (IV) complexes as a means of developing anticancer prodrugs that can target and selectively destroy cancer cells. Anticancer platinum (IV) prodrugs represent promising new strategies as targeted chemotherapeutic agents in the ongoing battle against cancer.

  13. The Dynamics of Platinum Precipitation in an Ion Exchange Membrane

    CERN Document Server

    Burlatsky, S F; Atrazhev, V V; Dmitriev, D V; Kuzminyh, N Y; Erikhman, N S

    2013-01-01

    Microscopy of polymer electrolyte membranes that have undergone operation under fuel cell conditions, have revealed a well defined band of platinum in the membrane. Here, we propose a physics based model that captures the mechanism of platinum precipitation in the polymer electrolyte membrane. While platinum is observed throughout the membrane, the preferential growth of platinum at the band of platinum is dependent on the electrochemical potential distribution in the membrane. In this paper, the location of the platinum band is calculated as a function of the gas concentration at the cathode and anode, gas diffusion coefficients and solubility constants of the gases in the membrane, which are functions of relative humidity. Under H2/N2 conditions the platinum band is located near the cathode-membrane interface, as the oxygen concentration in the cathode gas stream increases and/or the hydrogen concentration in the anode gas stream decreases, the band moves towards the anode. The model developed in this paper...

  14. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

    Science.gov (United States)

    Petrylak, Daniel P; de Wit, Ronald; Chi, Kim N; Drakaki, Alexandra; Sternberg, Cora N; Nishiyama, Hiroyuki; Castellano, Daniel; Hussain, Syed; Fléchon, Aude; Bamias, Aristotelis; Yu, Evan Y; van der Heijden, Michiel S; Matsubara, Nobuaki; Alekseev, Boris; Necchi, Andrea; Géczi, Lajos; Ou, Yen-Chuan; Coskun, Hasan Senol; Su, Wen-Pin; Hegemann, Miriam; Percent, Ivor J; Lee, Jae-Lyun; Tucci, Marcello; Semenov, Andrey; Laestadius, Fredrik; Peer, Avivit; Tortora, Giampaolo; Safina, Sufia; Del Muro, Xavier Garcia; Rodriguez-Vida, Alejo; Cicin, Irfan; Harputluoglu, Hakan; Widau, Ryan C; Liepa, Astra M; Walgren, Richard A; Hamid, Oday; Zimmermann, Annamaria H; Bell-McGuinn, Katherine M; Powles, Thomas

    2017-09-12

    Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m(2) plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96-4·47] vs 2·76 months [2·60-2·96]; hazard ratio [HR] 0·757, 95% CI 0·607-0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8-30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4-18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1

  15. Comparative studies of oxaliplatin-based platinum(iv) complexes in different in vitro and in vivo tumor models.

    Science.gov (United States)

    Göschl, Simone; Schreiber-Brynzak, Ekaterina; Pichler, Verena; Cseh, Klaudia; Heffeter, Petra; Jungwirth, Ute; Jakupec, Michael A; Berger, Walter; Keppler, Bernhard K

    2017-03-22

    Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines. Effects on the cell cycle were investigated by flow cytometry, and the capacity of inducing apoptosis was confirmed by flow cytometry and Western blotting. The anti-cancer activity of one complex was studied in vivo in immunodeficient and immunocompetent mice, and the platinum levels in various organs and the tumor after treatment were quantified. The results demonstrate that modification of the axial ligands can improve the cytotoxic potency. The complexes are able to interfere with plasmid DNA, which is enhanced by co-incubation with a reducing agent, and cause cell cycle perturbations. At higher concentrations, they induce apoptosis, but generate only low levels of reactive oxygen species. Two of the complexes increase the life span of leukemia (L1210) bearing mice, and one showed effects similar to oxaliplatin in a CT26 solid tumor model, despite the low platinum levels in the tumor. As in the case of oxaliplatin, activity in the latter model depends on an intact immune system. These findings show new perspectives for the development of platinum(iv) prodrugs of the anticancer agent oxaliplatin, combining bioreductive properties and immunogenic aspects.

  16. Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in locally advanced breast cancer: a Prospective Phase I trial

    Directory of Open Access Journals (Sweden)

    El-Sayed Mohamed I

    2010-08-01

    Full Text Available Abstract Background Neoadjuvant chemotherapy is the standard care for locally advanced breast cancer. Our study aimed at evaluating the feasibility of breast conversation surgery (BCS after neoadjuvant chemotherapy. Patients and methods Forty five patients had stage IIB (except those with T2N1 disease and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤5 cm underwent a tentative BCS while patients who had tumour size >5 cm underwent radical surgery. Negative margin is essential for BCS. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. Results Thirty four patients had BCS. Response to chemotherapy was the only statistically significant factor which influences the BCS. Incidence of local recurrence was 5.9% for patients who had BCS at a median follow up 24 months. Conclusion Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤4 cm after chemotherapy are the best candidates for BCS.

  17. Induction of immunogenic cell death by chemotherapeutic platinum complexes.

    Science.gov (United States)

    Wong, Daniel Yuan Qiang; Ong, Wendy Wei Fang; Ang, Wee Han

    2015-05-26

    There is compelling evidence suggesting that the immune-modulating effects of many conventional chemotherapeutics, including platinum-based agents, play a crucial role in achieving clinical response. One way in which chemotherapeutics can engage a tumor-specific immune response is by triggering an immunogenic mode of tumor cell death (ICD), which then acts as an "anticancer vaccine". In spite of being a mainstay of chemotherapy, there has not been a systematic attempt to screen both existing and upcoming Pt agents for their ICD ability. A library of chemotherapeutically active Pt agents was evaluated in an in vitro phagocytosis assay, and no correlation between cytotoxicity and phagocytosis was observed. A Pt(II) N-heterocyclic carbene complex was found to display the characteristic hallmarks of a type II ICD inducer, namely focused oxidative endoplasmic reticulum (ER) stress, calreticulin exposure, and both HMGB1 and ATP release, and thus identified as the first small-molecule immuno-chemotherapeutic agent.

  18. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    Science.gov (United States)

    Vyas, Nitin; Turner, Andrew; Sewell, Graham

    2014-09-15

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an estimate of the quantity of Pt discharged through the drains suggests that about 22% of total Pt is emitted to the environment from the hospital with the remainder being discharged by treated patients in the wider community. Administration figures for the three Pt-based drugs used in the hospital (cisplatin, carboplatin and oxaliplatin) coupled with published measurements on the removal of the drugs by conventional sewage treatment allowed the concentrations of Pt arising from each drug to be predicted in recipient surface waters as a function of water flow rate. For conditions representative of the region under study, concentrations of total Pt between a few tens and in excess of 100 pg L(-1) are predicted, with the principal form of the metal occurring as carboplatin and its metabolites. Although predicted concentrations are below EMEA guidelines warranting further risk assessment, the presence of substances in surface waters that are potentially carcinogenic, mutagenic and teratogenic and yet whose environmental effects are not understood is cause for concern. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer.

    Science.gov (United States)

    Lee, Maria; Kim, Sang Wun; Nam, Eun Ji; Yim, Ga Won; Kim, Sunghoon; Kim, Young Tae

    2011-08-01

    To evaluate the impact of both pretreatment thrombocytosis, and platelet count reduction post-adjuvant chemotherapy, on survival in patients with advanced epithelial ovarian cancer. Records of 179 women who underwent cytoreductive surgery for FIGO stage III or IV epithelial ovarian cancer and received six cycles of platinum/paclitaxel-based chemotherapy between July 1998 and March 2009 were retrospectively reviewed. Platelet ratio was defined as the preoperative platelet count divided by the platelet count after chemotherapy. The prognostic significance of thrombocytosis and platelet ratio, together with various clinicopathological factors, were evaluated by multivariate analysis. Sixty-two of 179 (34.6%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis had greater elevations of CA-125 (pthrombocytosis and CA-125 elevation retained significance as indicators of poor prognosis in patients with stage III or IV disease. In patients with normal CA-125 after chemotherapy, a high platelet ratio was an independent risk factor for reduced survival (p=0.05). Preoperative thrombocytosis and a high platelet ratio appear to be poor prognostic factors of survival in patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery and adjuvant platinum/paclitaxel-based chemotherapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Multi-drug delivery system based on alginate/calcium carbonate hybrid nanoparticles for combination chemotherapy.

    Science.gov (United States)

    Wu, Jin-Long; Wang, Chao-Qun; Zhuo, Ren-Xi; Cheng, Si-Xue

    2014-11-01

    A facile strategy to prepare nano-sized drug carriers for co-delivery of multiple types of drugs in combination chemotherapy was developed. Inorganic/organic hybrid alginate/CaCO3 nanoparticles were prepared by co-precipitation in an aqueous solution under very mild conditions. A hydrophilic drug (doxorubicin hydrochloride, DOX) and a hydrophobic drug (paclitaxel, PTX) were co-encapsulated in the hybrid nanoparticles. For comparison, PTX loaded nanoparticles and DOX loaded nanoparticles were also prepared. The measurement based on dynamic light scattering indicated all nanoparticles had a mean size less than 200 nm with a relatively narrow size distribution. The morphology of the nanoparticles was observed by TEM. The in vitro drug release study showed that the release of DOX and PTX from the dual drug loaded nanoparticles could be effectively sustained. The tumor cell inhibitory effect of the drug loaded nanoparticles was evaluated in HeLa cells and MCF-7/ADR cells. The dual drug loaded nanoparticles exhibited significantly enhanced cell uptake and nuclear localization as compared with the single drug loaded nanoparticles. As a result, the dual drug loaded nanoparticles had a significantly enhanced cell inhibitory effect, especially for drug resistant tumor cells. These results indicated that alginate/CaCO3 hybrid nanoparticles have promising applications for the co-delivery of drugs with different physicochemical properties in combination chemotherapy to overcome multidrug resistance.

  1. Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors

    Science.gov (United States)

    González, Iria; Del Castillo, Silvia; Muñiz, Javier; Morales, Luis J.; Moreno, Fernando; Jiménez, Rosa; Cristóbal, Carmen; Graupner, Catherine; Talavera, Pedro; Curcio, Alejandro; Martínez, Paula; Guerra, Juan A.; Alonso, Joaquín J.

    2015-01-01

    Introduction. Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. Methods. This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. Results. At the end of follow-up (median: 12 months, interquartile range: 11.1–12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04–1.36), and age: 1.12 (95% CI: 1.03–1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. Conclusion. Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. BMI

  2. Platinum-Catalyzed Selective Hydration of Hindered Nitriles and Nitriles with Acid- or Base-Sensitive Groups

    NARCIS (Netherlands)

    Jiang, Xiao-bin; Minnaard, Adriaan J.; Vries, Johannes G. de; Feringa, Bernard

    2004-01-01

    Hindered tertiary nitriles can be hydrolyzed under neutral and mild conditions to the corresponding amides using platinum(II) catalysts with dimethylphosphine oxide or other secondary phosphine oxides (SPOs, phosphinous acids) as ligands. We have found that this procedure also works well for

  3. A comparative study on the influence of the platinum catalyst in poly(dimethylsiloxane) based networks synthesis

    DEFF Research Database (Denmark)

    Bejenariu, Anca Gabriela; Poulsen, Julie Øblom; Skov, Anne Ladegaard

    2009-01-01

    The aim of the project is to find the best of three Pt catalysts and their appropriate quantity in order to obtain soft networks in one hour at room temperature. How the choice of catalyst influences the final elastomeric properties is also evaluated. The differences between the catalysts are the...... are the solvent and the platinum concentration....

  4. Novel 3-(aminomethyl)naphthoquinone mannich base-platinum(IV) complexes: synthesis, characterization, electrochemical and cytotoxic studies

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Gustavo B. da; Neves, Amanda P.; Vargas, Maria D., E-mail: mdvargas@vm.uff.br [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Instituto de Quimica; Alves, Wagner A. [Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropedica, RJ (Brazil). Departamento de Quimica; Marinho-Filho, Jose D.B.; Pessoa, Claudia; Moraes, Manoel O.; Costa-Lotufo, Leticia V. [Universidade Federal do Ceara (UFCE), Fortaleza, CE (Brazil). Centro de Ciencias da Saude. Departamento de Fisiologia e Farmacologia

    2013-04-15

    Three novel platinum(IV) complexes cis,cis,trans-[Pt(HL1-3)Cl{sub 2}(OH){sub 2}] 1b-3b(HL = 2-hydroxy-3-[(R{sup 1} -amino)(pyridin-2-yl)methyl]-1,4-naphthoquinone, R{sup 1} = n-butyl, HL1; n-heptyl, HL2 and n-decyl, HL3) have been obtained from the oxidation of the respective precursors cis-[Pt(HL1-3)Cl{sub 2}] 1a-3a. Cyclic voltammetry studies of 1b-3b in MeCN showed the quasi reversible naphthoquinonate (NQO{sup -}, i.e., L{sup -}) redox process and irreversible process attributed to the reduction of the Pt{sup 4+}/Pt{sup 2+} pair, at potentials about 400 mV less negative than for the cisplatin precursor cis,cis,trans-[Pt(NH{sub 3}){sub 2}Cl{sub 2}(OH){sub 2}]. Hydrogen bond interaction between the naphthoquinone 2-hydroxyl group and an axially coordinated hydroxide ligand in 1b-3b has been proposed to favor the Pt{sup 4+}/Pt{sup 2+} reduction. The cytotoxicity studies against four human cancer cell lines have shown that in general the platinum(IV) and platinum(II)derivatives exhibit the same cytotoxic profile and are all more active than cisplatin. The lowest in vitro IC{sub 50} values have been observed for 2b-3b, which bear ligands with the largest R{sup 1} groups (HL2-HL3) being the most lipophilic. Furthermore similar IC{sub 50} values for platinum(II) and platinum(IV) complexes of the same ligands have been associated with rapid in vitro reduction of the latter complexes to afford 1a-3a. (author)

  5. Behind platinum's sparkle.

    Science.gov (United States)

    Yam, Vivian W W

    2010-09-01

    As a rare and precious metal that is also resistant to wear and tarnish, platinum is known to be particularly well-suited to jewellery. Vivian Yam reflects on how, beyond its prestigious image, platinum has also found its way into a variety of fields ranging from the petrochemical to the pharmaceutical industry.

  6. Cancer Chemotherapy

    Science.gov (United States)

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  7. Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

    Science.gov (United States)

    Nadin, Silvina B; Sottile, Mayra L; Montt-Guevara, Maria M; Gauna, Gisel V; Daguerre, Pedro; Leuzzi, Marcela; Gago, Francisco E; Ibarra, Jorge; Cuello-Carrión, F Darío; Ciocca, Daniel R; Vargas-Roig, Laura M

    2014-07-01

    Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated, by immunohistochemistry, the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n = 60) treated with doxorubicin (DOX)- or epirubicin (EPI)-based monochemotherapy. Serial biopsies were taken at days 1, 3, 7, and 21, and compared with prechemotherapy and surgical biopsies. After surgery, the patients received additional chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P 31 % of the cells) and cytoplasmic HSPA expressions (>11 % of the tumor cells) were associated with better DFS (P = 0.0348 and P = 0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy indicating the need to change the administered drugs after surgery for overcoming drug resistance.

  8. The efficacy and safety of panitumumab plus irrinotecan-based chemotherapy in the treatment of metastatic colorectal cancer

    Science.gov (United States)

    Chen, Qiang; Cheng, Minjing; Wang, Zhuo; Zhao, Shipeng

    2016-01-01

    Abstract Background: Panitumumab, a fully human monoclonal antibody targeting epidermal growth factor receptor, is used in combination with chemotherapy for patients with metastatic colorectal cancer (mCRC). However, the effects of panitumumab in combination with irrinotecan-based chemotherapy remain uncertain. Therefore, we conducted this meta-analysis to assess the efficacy and safety of combination treatment of panitumumab plus chemotherapy in the treatment of mCRC. Methods: By searching electronic databases (PubMed, Embase, and Web of Science), all clinical trials which assessed the effects of panitumumab plus irrinotecan-based chemotherapy in mCRC would be included. Main outcome measures included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and adverse events. Pooled estimates were calculated by a fixed-effects model or random-effects model, according to the heterogeneity among the included studies. Results: Eleven trials with a total number of 1338 patients met the inclusion criteria and were included in this meta-analysis. The combination treatment of panitumumab and irrinotecan-based chemotherapy was associated with a median PFS of 5.83 months, OS of 11.15 months, and ORR of 33%. Subgroup analysis showed that, in the first-line and second-line treatment, the combination therapy for PFS was 9.27 and 5.01 months, for OS was 8.87 and 11.68 months, and for ORR was 61% and 26%, respectively. In the wild-type and mutant KRAS populations, the combination therapy for PFS was 5.76 and 5.27 months, for OS was 11.15 and 10.64 months, and for ORR was 37% and 18%, respectively. Moreover, combination therapy also induced an incidence of 56% treatment-related adverse events. Conclusion: Panitumumab plus irrinotecan-based chemotherapy is effective and well-tolerated in the treatment of patients with mCRC, especially in those with wild-type KRAS tumors. PMID:27977573

  9. Successful treatment with pemetrexed, Carboplatin, and bevacizumab for platinum-resistant adenocarcinoma of the lung.

    Science.gov (United States)

    Wada, Sae; Fujimoto, Nobukazu; Gemba, Kenichi; Asano, Michiko; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kishimoto, Takumi

    2012-01-01

    WE PRESENT TWO CASES OF RELAPSED ADENOCARCINOMA OF THE LUNG: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  10. Successful Treatment with Pemetrexed, Carboplatin, and Bevacizumab for Platinum-Resistant Adenocarcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Sae Wada

    2012-01-01

    Full Text Available We present two cases of relapsed adenocarcinoma of the lung: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  11. Palladium and platinum-based nanoparticle functional sensor layers for selective H2 sensing

    Energy Technology Data Exchange (ETDEWEB)

    Ohodnicki, Jr., Paul R.; Baltrus, John P.; Brown, Thomas D.

    2017-07-04

    The disclosure relates to a plasmon resonance-based method for H.sub.2 sensing in a gas stream utilizing a hydrogen sensing material. The hydrogen sensing material is comprises Pd-based or Pt-based nanoparticles having an average nanoparticle diameter of less than about 100 nanometers dispersed in an inert matrix having a bandgap greater than or equal to 5 eV, and an oxygen ion conductivity less than approximately 10.sup.-7 S/cm at a temperature of 700.degree. C. Exemplary inert matrix materials include SiO.sub.2, Al.sub.2O.sub.3, and Si.sub.3N.sub.4 as well as modifications to modify the effective refractive indices through combinations and/or doping of such materials. The hydrogen sensing material utilized in the method of this disclosure may be prepared using means known in the art for the production of nanoparticles dispersed within a supporting matrix including sol-gel based wet chemistry techniques, impregnation techniques, implantation techniques, sputtering techniques, and others.

  12. Characterization of the surfaces of platinum/tin oxide based catalysts by Fourier transform spectroscopy (FTIR)

    Science.gov (United States)

    Keiser, Joseph T.

    1989-01-01

    The Laser Atmospheric Wind Sounder (LAWS) Program has as one of its goals the development of a satellite based carbon dioxide laser for making wind velocity measurements. The specifications for this laser include the requirement that the laser operate at a repetition rate of 10 Hertz continuously for three years. Earth-based carbon dioxide lasers can operate for only a short time on a single charge of gas because the lasing action causes the CO2 to break down into CO and O2. Therefore, earth-based CO2 lasers are generally operated in a flow through mode in which the spent gas is continually exhausted and fresh gas is continually added. For a satellite based system, however, a recirculation system is desired because it is not practical to send up extra tanks of CO2. A catalyst which could enable a recirculating CO2 laser to function continuously for three years needs to be developed. In the development of a catalyst system there are many variables. Obviously, not all possible formulations can be tested for three years, therefore, an accurate model which is based on the reaction mechanism is needed. The construction of a multistep reaction mechanism is similar to the construction of a jigsaw puzzle. Different techniques each supply a piece of the puzzle and the researcher must put the pieces together. Transmission infrared spectroscopy was shown to be very useful in supplying some of the information needed to elucidate reaction mechanisms. The purpose was to see what kind of information might be obtained about the NASA catalyst using infrared absorption spectroscopy. Approximately 200 infrared spectra of the prototype Pt/tin oxide catalyst and its precursor components are observed under a variety of different conditions. The most significant observations are summarized.

  13. [The effect of the histoculture drug response assay (HDRA) based perioperative chemotherapy for non-small cell lung cancer].

    Science.gov (United States)

    Tanahashi, Masayuki; Yamada, T; Moriyama, S; Suzuki, E; Niwa, H

    2008-01-01

    In this study we analyze the usefulness of the histoculture drug response assay (HDRA) based perioperative chemotherapy for non-small cell lung cancer. From 2001 to 2006, we examined the chemosensitivity of 70 lung cancer tissues to cisplatin (CDDP), carboplatin (CBDCA), paclitaxel, docetaxel, gemcitabine and irinotecan. In 16 patients with stage III lung cancer who treated induction therapy, the response rate was 100% of 5 patients treated chemotherapy using 2 HDRA-positive drugs, 50% of 8 patient treeated using 1 positive drugs and 0% of 3 patients treated using negative drugs, respectively. The 3-year survival rate of the 5 patients treated using 2 positive drugs was better than that of 11 patient treated using 1 or non positive drugs (p = 0.07). In 39 patients with stage III lung cancer who treated adjuvant chemotherapy, the survival rate of the 14 patients treated chemotherapy using 2 positive drugs was significantly better than that of 25 patients treated using 1 or non positive drugs (p = 0.03). Therefore, HDRA may useful to the improvement of the response to chemotherapy and survival.

  14. Label-free DNA biosensor based on resistance change of platinum nanoparticles assemblies.

    Science.gov (United States)

    Skotadis, Evangelos; Voutyras, Konstantinos; Chatzipetrou, Marianneza; Tsekenis, Georgios; Patsiouras, Lampros; Madianos, Leonidas; Chatzandroulis, Stavros; Zergioti, Ioanna; Tsoukalas, Dimitris

    2016-07-15

    A novel nanoparticle based biosensor for the fast and simple detection of DNA hybridization events is presented. The sensor utilizes hybridized DNA's charge transport properties, combining them with metallic nanoparticle networks that act as nano-gapped electrodes. The DNA hybridization events can be detected by a significant reduction in the sensor's resistance due to the conductive bridging offered by hybridized DNA. By modifying the nanoparticle surface coverage, which can be controlled experimentally being a function of deposition time, and the structural properties of the electrodes, an optimized biosensor for the in situ detection of DNA hybridization events is ultimately fabricated. The fabricated biosensor exhibits a wide response range, covering four orders of magnitude, a limit of detection of 1nM and can detect a single base pair mismatch between probe and complementary DNA.

  15. Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy

    Directory of Open Access Journals (Sweden)

    Shao IH

    2014-10-01

    Full Text Available I-Hung Shao,1,2,* Yu-Hsiang Lin,1,* Chen-Pang Hou,1 Horng-Heng Juang,3,4 Chien-Lun Chen,1 Phei-Lang Chang,1,4 Ke-Hung Tsui, 1,41Department of Urology, Chang Gung Memorial Hospital at Linkou, Chang Gung University, 2Department of Urology, Lotung Poh-Ai Hospital, 3Department of Anatomy, Chang Gung University, 4Bioinformation Center, Chang Gung Memory Hospital, Kwei-Shan, Tao-Yuan, Taiwan, Republic of China*These authors contributed equally to this workPurpose: Radical nephroureterectomy (RNU is a standard treatment for upper urinary tract urothelial carcinoma. However, RNU can result in decreased renal function and cannot be treated with adjuvant chemotherapy. We performed a risk group stratification analysis to determine the preoperative factors that are predictive of diminished renal function after RNU.Materials and methods: We retrospectively evaluated the medical records of all patients who underwent nephroureterectomy for upper urinary tract urothelial carcinoma at the Chang Gung Memorial Hospital from 2001 to 2008. We analyzed the association between perioperative glomerular filtration rate and preoperative parameters including cancer characteristics, serum creatinine level, and kidney size measured on computed tomographic images.Results: A total of 242 patients fulfilled the inclusion criteria. The average decrease in renal function 1 month after RNU was 19.7%. Using 60 mL/min/1.73 m2 as the eligibility cutoff for cisplatin-based chemotherapy, 42.1% of the population was eligible prior to nephroureterectomy, whereas following surgery only 15.2% remained eligible. Using a cutoff of 45 mL/min/1.73 m2, 59.9% of the cohort was eligible for fractionated cisplatin dosing preoperatively, whereas only 32.6% remained above the cutoff postoperatively. The most significant predictors of poor postoperative renal function were body mass index >25 kg/m2, age >65 years, contralateral kidney length less than 10 cm, and absence of ipsilateral hydronephrosis

  16. Gamma Prime Morphology and Creep Properties of Nickel Based Superalloys With Platinum Group Metal Additions (Preprint)

    Science.gov (United States)

    2008-04-01

    creep resistance. Polycrystalline superalloy MAR - M247 can sustain a creep rate of 10-8 s-1 at 982°C at a stress of 172 MPa [44], while the alloys...Nathal, R.D. Maier, and L.J. Ebert, “The Influence of Cobalt on the Tensile and Stress Rupture Properties of the Nickel-Base Superalloy MAR - M247 ,” Metallurgical Transactions A, 13 (A) (1982), 1767-1774.           10

  17. 参附注射液联合含铂一线化疗方案治疗非小细胞肺癌的Meta分析%Meta-analysis on Treatment of Non-small Cell Lung Cancer with Shenfu Injection in Combination with Platinum-contained First-fine Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    何海浪; 王谦; 赵阳; 刘会平; 曹振东; 周贤梅

    2013-01-01

    Objective:To study the efficacy and safety of Shenfu injection (SFI) in combination with platinum-contained first-line chemotherapy in treating non-small cell lung cancer (NSCLC).Method:Cochrane library,PubMed,CBM,CNKI,VIP,WANFANG DATA and Traditional Chinese Medicine Database System were searched through computers.The search was finished in September,2012.Randomized controlled trials (RCTs) of SFI in combination with platinum-contained first-line chemotherapy (versus chemotherapy alone) in any language were included.Two researchers extracted data and assess literature quality separately,and made a metaanalyses by RevMan 5.1 software.Result:A Total of 19 RCTs was included.The Meta-analysis showed thatcompared with the pure application of platinum-contained first-line chemotherapy,the combination of SFI and chemotherapy can not enhance the near-term curative effect [OR =1.41,95% CI (0.98,2.02),P =0.06],but may improve the quality of life [OR =2.72,95% CI (1.48,5.00),P =0.001],enhance CD3 + [SMD =0.41,95% CI (0.10,0.71),P =0.008],CD4 + [SMD =7.58,95% CI (4.32,10.84),P <0.00001] and CD4+/CD8+ [SMD =9.89,95% CI (4.76,15.02),P =0.000 2] and reduced WBC toxicity[RR=0.35,95% CI (0.23,0.54),P <0.000 01],Hemoglobin toxicity (RR =0.41,95% CI:0.20~ 0.83,P =0.01),Platelet toxicity [RR =0.34,95% CI (0.18,0.65),P =0.001],the gastrointestinal reactions [RR =0.24,95% CI (0.13,0.45),P < 0.000 01)].Conclusion:The current evidence indicates that SFI can not enhance the chemotherapeutic effect on NSCLC patients,but may improve the quality of life and reduce adverse effect of contained therapy of platinum and chemotherapeutics.These results require confirmation with rigorously controlled trials.%目的:系统评价参附注射液联合含铂一线化疗方案治疗非小细胞肺癌(Non-small cell lung carcinoma,NSCLC)的有效性及安全性.方法:计算机检索Cochrane Library,PubMed,CBM,CNKI,VIP,万方数据库,中国中医药数据库等数据库,检索

  18. Chemotherapy-induced nausea and vomiting in daily clinical practice: a community hospital-based study

    NARCIS (Netherlands)

    Hilarius, D.L; Kloeg, P.H.; van der Wall, E.; van den Heuvel, J.J.G.; Gundy, C.M.; Aaronson, N.K.

    2012-01-01

    Background Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. This study investigated: (1) the impact of CINV on patients' health-related quality of life (HRQL) in daily clinical practice; (2) the association between patient characteristics and type of

  19. Optical measurements of platinum based electrocatalysts for the electrooxidation of methanol

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, K. [Institute for Analytical and Chemical Technologies, Department of Electrochemistry, Vienna University of Technology, A-1060 Vienna (Austria); Kronberger, H.; Fafilek, G. [ECHEM Centre of Competence in Applied Electrochemistry, Wiener Neustadt (Austria); Institute for Analytical and Chemical Technologies, Department of Electrochemistry, Vienna University of Technology, A-1060 Vienna (Austria); Nauer, G. [ECHEM Centre of Competence in Applied Electrochemistry, Wiener Neustadt (Austria); Institute of Physical Chemistry, University of Vienna, Vienna (Austria); Besenhard, J.O. [ECHEM Centre of Competence in Applied Electrochemistry, Wiener Neustadt (Austria); Institute of Chemical Technology of Inorganic Materials, Graz University of Technology, Graz (Austria)

    2003-08-01

    In a combinatorial electrochemistry experiment quinine was used as a pH sensitive fluorescing indicator to detect the catalytic activity of methanol oxidation catalysts. During electrochemical experiments the surface of the electrode array was monitored with a CCD camera. The dependence of the intensity of the fluorescence on the applied potential was used as an analytical tool; to investigate the electrochemical performance of Pt based electrocatalysts, for the electrooxidation of methanol, in both short and long term tests. (Abstract Copyright [2003], Wiley Periodicals, Inc.)

  20. Exploiting developments in nanotechnology for the preferential delivery of platinum-based anti-cancer agents to tumours: targeting some of the hallmarks of cancer.

    Science.gov (United States)

    Parker, James P; Ude, Ziga; Marmion, Celine J

    2016-01-01

    Platinum drugs as anti-cancer therapeutics are held in extremely high regard. Despite their success, there are drawbacks associated with their use; their dose-limiting toxicity, their limited activity against an array of common cancers and patient resistance to Pt-based therapeutic regimes. Current investigations in medicinal inorganic chemistry strive to offset these shortcomings through selective targeting of Pt drugs and/or the development of Pt drugs with new or multiple modes of action. A comprehensive overview showcasing how liposomes, nanocapsules, polymers, dendrimers, nanoparticles and nanotubes may be employed as vehicles to selectively deliver cytotoxic Pt payloads to tumour cells is provided.

  1. Theoretical investigations and density functional theory based quantitative structure-activity relationships model for novel cytotoxic platinum(IV) complexes.

    Science.gov (United States)

    Varbanov, Hristo P; Jakupec, Michael A; Roller, Alexander; Jensen, Frank; Galanski, Markus; Keppler, Bernhard K

    2013-01-10

    Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure-activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors.

  2. Theoretical Investigations and Density Functional Theory Based Quantitative Structure–Activity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes

    Science.gov (United States)

    2012-01-01

    Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure–activity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors. PMID:23214999

  3. Fabrication of platinum-decorated single-walled carbon nanotube based hydrogen sensors by aerosol jet printing.

    Science.gov (United States)

    Liu, Rui; Ding, Haiyan; Lin, Jian; Shen, Fangping; Cui, Zheng; Zhang, Ting

    2012-12-21

    The coffee ring effect is reduced effectively and a hydrogen sensor with platinum-decorated single-walled carbon nanotubes (SWCNTs) is prepared by aerosol jet printing (AJP) technology. The stable aqueous solution of platinum functional SWCNTs is prepared by a series of chemical and physical processes and the electrode array is formed by micro-fabrication technology. The AJP process is also researched in detail including the number of printing passes and the printing distance between electrodes. Then, the functional SWCNT aqueous solution is printed on the electrode array and the response of this sensor to the hydrogen is measured carefully. The results show that a functional SWCNT sensor has excellent sensing properties toward hydrogen.

  4. Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders of induction chemotherapy-based larynx preservation protocols.

    Science.gov (United States)

    Vourexakis, Zacharias; Le Ridant, Anne-Marie; Dulguerov, Pavel; Janot, François

    2015-07-01

    Induction chemotherapy-based larynx preservation protocols use chemotherapy to select exclusively patients with 'chemosensitive' tumors for a nonsurgical treatment with radiation therapy. This study on pyriform sinus squamous cell carcinoma (SCC) is interested in the oncological outcome of treatment based on radiation therapy when offered to patients with tumors responding to induction chemotherapy. This was a retrospective cohort study. The cohort included good responders to induction chemotherapy, subsequently treated with definite radiation therapy (with or without concomitant chemotherapy) for pyriform sinus SCC, in a tertiary referral cancer center. The primary endpoints were overall, laryngectomy-free and disease-free survival and the secondary endpoints were analysis of treatment failures and possibilities of salvage treatment. Forty-two patients fulfilled the inclusion criteria and were retained for analysis; 7% were stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5 years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ≈ 0.08), respectively. For the same intervals, the laryngectomy-free survival was 90% (38/42), 69% (29/42) and 50% (SE ≈ 0.08), respectively. The estimated 5-year disease-free survival was also 50%. Disease-free survival was significantly better for N0 patients. There was a 28% recurrence rate, mainly in the primary tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly, more than one-third of all oncologic failures occurred beyond the first 3 years of follow-up. Salvage treatment was not possible or definitely inefficient in at least 2/3 of all recurrences. In candidates for larynx preservation for a pyriform sinus SCC, good response to induction chemotherapy followed by definite radiation therapy seems to be associated with a more favorable prognosis. Nevertheless, in case of locoregional recurrence the possibilities for efficient salvage treatment are limited.

  5. Influences of Platinum Precursors and Solution Acidities on REO-Based Catalysts Performances

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Important effects exist between precious metals and rare earths oxides in three-way catalyst, especially the coordinated effects. These effects were studied by using H2PtCl6, Pt(NH3)2(NO2)2 and Pt(OH)2(C2H5ONH2)2 as Pt precursors, and the mixed oxide of (Ce-Zr-La-Pr)O as base material to prepare a series of catalysts, and their performances of the catalysts were studied by TPR and CO pulse titration technologies. The results shown that Pt precursors and their solutions pH values influenced the oxygen storage capabilities, the active metal distribution degrees of the catalysts obviously, and every catalyst prepared by different precursors had an optimal pH values. It indicates that the active metals precursors and their solutions acidities have outstanding influences on the catalysts performances for the mutual effects existing between the active metals and the Rare Earth metal oxides, which results from the mate groups of the precursors and the solution acidity.

  6. Optimizing treatment of the partially platinum-sensitive ovarian cancer patient.

    Science.gov (United States)

    Colombo, Nicoletta

    2013-12-01

    Ovarian cancer is the leading cause of gynecological cancer deaths worldwide. Despite primary treatment with platinum-containing regimens, the majority of women will experience recurrent disease and subsequent death. Recurrent ovarian cancer remains a challenge for successful management, and the choice of second-line chemotherapy is complex due to the range of different factors that need to be considered. One of the main considerations is the platinum-free interval and, specifically, the optimal treatment for patients who are partially platinum-sensitive (platinum-free interval: 6-12 months). Data from the large, multicenter, randomized OVA-301 study have shown that combined trabectedin-pegylated liposomal doxorubicin (PLD) significantly prolonged median overall survival compared with PLD alone (p = 0.0027) in 214 patients with partially platinum-sensitive advanced relapsed ovarian cancer. Furthermore, in OVA-301 patients with partially platinum-sensitive disease who received platinum therapy immediately after disease progression (n = 94), final median overall survival was improved by 9 months (p = 0.0153) in trabectedin-PLD patients compared with PLD alone. In addition to demonstrating a survival advantage, trabectedin-PLD may also allow the treatment of patients having not yet recovered from previous platinum toxicity. In summary, the data suggest the use of combined trabectedin-PLD as a second-line treatment option in patients with partially platinum-sensitive recurrent ovarian cancer, followed by a third-line platinum-containing regimen.

  7. Parametric study of the partial oxidation of propane over nickel and platinum based catalysts

    Science.gov (United States)

    Mukka, Mayuri

    supported by both the catalysts are completely different. For the Pt-based catalysts, hydrogen is formed directly by the exothermic partial-oxidation route at lower contact times. This is consistent with earlier work in our laboratory. On the other hand, for Ni-based catalysts, hydrogen is formed by the endothermic steam-reforming reaction which occurs after total oxidation. The 1%Pt/CeO2 catalyst favors higher hydrogen production at lower contact times, whereas the 1%Ni/CeO 2 catalyst favors higher hydrogen production at higher contact times. These results suggest that the 1%Pt/CeO2 catalysts could be used in micro-reactors, at low contact times. On the other hand, since the 1%Ni/CeO 2 catalyst favors the indirect partial oxidation pathway through the endothermic steam reforming process (which is in-turn driven by the heat and products from the total oxidation reaction) and supports higher hydrogen production at higher contact times, large scale reactors or industrial reactors providing larger contact times would be more effective for the 1%Ni/CeO2 catalyst.

  8. Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiaoping; Bai Zhibin; Chen Baoan; Feng Jifeng; Yan Feng; Jiang Zhi; Zhong Yuejiao

    2014-01-01

    Background The importance of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear.The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy.DNA samples were isolated from peripheral blood collected before treatment.The three single nucleotide polymorphisms (SNPs) (rs1801131,rs1801133,rs2274976) genotypes of the MTHFR gene were determined by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Results The average response rate for chemotherapy was 46.7%.Homozygous genotypes rs2274976G/G (x2=22.7,P <0.01) and rs1801131A/A (x2=14.3,P=0.008) were over-represented in responsive patients.Carriers of the rs2274976A allele genotypes (G/A and A/A) and of the rs1801131C allele genotypes (A/C and C/C) were prevalent in nonresponsive patients.In the haplotype association analysis,there was a significant difference in global haplotype distribution between the groups (x2=20.69,P=0.000 124).Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population.Well-designed,comprehensive,and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.

  9. The status of platinum anticancer drugs in the clinic and in clinical trials.

    Science.gov (United States)

    Wheate, Nial J; Walker, Shonagh; Craig, Gemma E; Oun, Rabbab

    2010-09-21

    Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, Lipoplatin and ProLindac). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade.

  10. Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

    Directory of Open Access Journals (Sweden)

    Pavel Štarha

    2015-01-01

    Full Text Available The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH32Cl2], CDDP, are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid and functionalized by activated cisplatin in the form of cis-[Pt(NH32(H2O2]2+ (CDDP*. The relevant techniques (XPS, EDS, ICP-MS proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by 57Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe3+ centers of maghemite, as compared to maghemite nanoparticles (mag, were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0, phosphate (pH 7.0 and carbonate (pH 9.0 buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem.

  11. Fighting Cancer Together: Development and Implementation of Shared Medical Appointments to Standardize and Improve Chemotherapy Education

    Science.gov (United States)

    Prescott, Lauren S.; Dickens, Andrea S.; Guerra, Sandra L.; Tanha, Jila M.; Phillips, Desiree G.; Patel, Katherine T.; Umberson, Katie M.; Lozano, Miguel A.; Lowe, Kathryn B.; Brown, Alaina J.; Taylor, Jolyn S.; Soliman, Pamela T.; Garcia, Elizabeth A.; Levenback, Charles F.; Bodurka, Diane C.

    2015-01-01

    Objective Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. Methods We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. Results From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. Conclusions This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted. PMID:26549108

  12. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide.

    Science.gov (United States)

    Serpe, Loredana; Gallicchio, Margherita; Canaparo, Roberto; Dosio, Franco

    2014-01-01

    Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.

  13. Platinum hypersensitivity and desensitization.

    Science.gov (United States)

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

    Science.gov (United States)

    Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

    2014-01-01

    The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.

  15. Detection of mercury ions based on mercury-induced switching of enzyme-like activity of platinum/gold nanoparticles

    Science.gov (United States)

    Tseng, Chao-Wei; Chang, Hsiang-Yu; Chang, Jia-Yaw; Huang, Chih-Ching

    2012-10-01

    In this study, bimetallic platinum/gold nanoparticles (Pt/Au NPs) were found to exhibit peroxidase-like activity, and the deposition of mercury was found to switch the enzymatic activity to a catalase-like activity. Based on this phenomenon, we developed a new method for detecting mercury ions through their deposition on bimetallic Pt/Au NPs to switch the catalytic activity of Pt/Au NPs. Pt/Au NPs could be easily prepared through reduction of Au3+ and Pt4+ by sodium citrate in a one-pot synthesis. The peroxidase catalytic activity of the Pt/Au NPs was controlled by varying the ratios of Pt to Au. The Pt0.1/Au NPs (prepared with a [Au3+]/[Pt4+] molar ratio of 9.0/1.0) showed excellent oxidation catalysis for H2O2-mediated oxidation of Amplex® Red (AR) to resorufin. The oxidized product of AR, resorufin, fluoresces more strongly (excitation/emission wavelength maxima ca. 570/585 nm) than AR alone. The peroxidase catalytic activity of Pt0.1/Au NPs was switched to catalase-like activity in the presence of mercury ions in a 5.0 mM tris(hydroxymethyl)aminomethane (Tris)-borate solution (pH 7.0) through the deposition of Hg on the particle surfaces owing to the strong Hg-Au metallic bond. The catalytic activity of Hg-Pt0.1/Au NPs is superior (by at least 5-fold) to that of natural catalase (from bovine liver). Under optimal solution conditions [5.0 mM Tris-borate (pH 7.0), H2O2 (50 mM), and AR (10 μM)] and in the presence of the masking agents polyacrylic acid and tellurium nanowires, the Pt0.1/Au NPs allowed the selective detection of inorganic mercury (Hg2+) and methylmercury ions (MeHg+) at concentrations as low as several nanomolar. This simple, fast, and cost-effective system enabled selective determination of the spiked concentrations of Hg2+ and MeHg+ in tap, pond, and stream waters.In this study, bimetallic platinum/gold nanoparticles (Pt/Au NPs) were found to exhibit peroxidase-like activity, and the deposition of mercury was found to switch the enzymatic

  16. Heterogeneous platinum-catalyzed hydrogenation of dialkyl(diolefin)platinum(II) complexes: A new route to platinum surface alkyls

    OpenAIRE

    McCarthy, Thomas J.; Shih, Yen-Shiang; Whitesides, George M.

    1981-01-01

    Platinum metal catalyzes the reduction of dialkyl(diolefin)platinum(II) complexes by dihydrogen to alkanes and platinum(0). The reaction involves adsorption of the platinum(II) complex on the platinum(0) catalyst surface with conversion of the alkyl moieties to platinum surface alkyls; these appear as alkane products. The platinum atom originally present in the soluble organoplatinum species becomes part of the platinum(0) surface.

  17. The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

    Science.gov (United States)

    Woolston, Caroline M; Zhang, Lei; Storr, Sarah J; Al-Attar, Ahmad; Shehata, Mohamed; Ellis, Ian O; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments. PMID:22481283

  18. Symptom cluster analyses based on symptom occurrence and severity ratings among pediatric oncology patients during myelosuppressive chemotherapy.

    Science.gov (United States)

    Baggott, Christina; Cooper, Bruce A; Marina, Neyssa; Matthay, Katherine K; Miaskowski, Christine

    2012-01-01

    Symptom cluster research is an emerging field in symptom management. The ability to identify symptom clusters that are specific to pediatric oncology patients may lead to improved understanding of symptoms' underlying mechanisms among patients of all ages. The purpose of this study, in a sample of children and adolescents with cancer who underwent a cycle of myelosuppressive chemotherapy, was to compare the number and types of symptom clusters identified using patients' ratings of symptom occurrence and symptom severity. Children and adolescents with cancer (10-18 years of age; N = 131) completed the Memorial Symptom Assessment Scale 10-18 on the day they started a cycle of myelosuppressive chemotherapy, using a 1-week recall of experiences. Symptom data based on occurrence and severity ratings were examined using exploratory factor analysis. The defined measurement model suggested by the best exploratory factor analysis model was then examined with a latent variable analysis. Three clusters were identified when symptom occurrence ratings were evaluated, which were classified as a chemotherapy sequela cluster, mood disturbance cluster, and a neuropsychological discomfort cluster. Analysis of symptom severity ratings yielded similar cluster configurations. Cluster configurations remained relatively stable between symptom occurrence and severity ratings. The evaluation of patients at a common point in the chemotherapy cycle may have contributed to these findings. Additional uniformity in symptom clusters investigations is needed to allow appropriate comparisons among studies. The dissemination of symptom cluster research methodology through publication and presentation may promote uniformity in this field.

  19. The effect of trastuzumab-based chemotherapy in small node-negative HER2-positive breast cancer.

    Science.gov (United States)

    van Ramshorst, Mette S; van der Heiden-van der Loo, Margriet; Dackus, Gwen M H E; Linn, Sabine C; Sonke, Gabe S

    2016-07-01

    The prognosis of patients with stage II-III Human Epidermal growth factor Receptor 2 (HER2)-positive breast cancer has significantly improved since the addition of trastuzumab to (neo-)adjuvant chemotherapy. Several reports have shown that small (≤2 cm), node-negative, HER2-positive tumors have a relatively poor prognosis and these patients increasingly receive trastuzumab-based chemotherapy. We aimed to provide evidence for this approach in a population-based cohort. All T1N0M0 HER2-positive breast cancer patients diagnosed between 2006 and 2012 were identified from the Netherlands Cancer Registry. Patient, tumor, and treatment characteristics were recorded. Kaplan-Meier statistics were used for overall survival (OS) and breast cancer-specific survival (BCSS) estimations overall and in T1a, T1b, and T1c tumors separately. Cox regression analyses were performed to account for imbalances in baseline characteristics between treated and untreated patients. A total of 3512 patients were identified: 385 with T1a, 800 with T1b, and 2327 with T1c tumors. Forty-five percent of patients received chemotherapy and/or trastuzumab: 92 % received both. Chemotherapy and/or trastuzumab significantly improved 8-year OS (95 vs. 84 %; hazard ratio [HR] 0.29; 95 % confidence interval [CI] 0.21-0.41, P effect remained significant in multivariable analyses (HR 0.35; 95 % CI 0.23-0.52, P effect on OS and BCSS was similar in T1a, T1b, and T1c tumors. Chemotherapy and/or trastuzumab improves OS and BCSS and can be considered in all patients with small node-negative HER2-positive breast cancer.

  20. The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC)

    Science.gov (United States)

    Yang, Jiaying; He, Jieyu; Yu, Miao; Li, Taishun; Luo, Li; Liu, Pei

    2016-01-01

    Abstract Background: Trials investigating the efficacy and safety of combining molecular targeted agent (MTA) with platinum–gemcitabine (PG) in first-line treatment of advanced non-small cell lung cancer (NSCLC) have shown inconsistent findings. This meta-analysis aimed to explore whether the addition of MTAs to PG in NSCLC could provide a survival benefit with a tolerable toxicity. Methods: Web of knowledge, PubMed, Ovid, Embase, and Cochrane Library were searched to identify relevant studies and extract data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and common grade 3 or 4 adverse events. Subgroup analyses were conducted on the basis of race and the type of MTA. Results: Twelve trials with a total of 6143 patients were included in this meta-analysis. Compared with PG chemotherapy, combination therapy of MTA with PG did not improve OS (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.90–1.01) but improved PFS (HR = 0.77, 95% CI = 0.66–0.89) and ORR (risk ratio [RR] = 1.33, 95% CI = 1.11–1.60). Subanalysis indicated that there was more incidence of grade 3 or 4 rash (RR = 11.20, 95% CI = 6.07–20.68), anemia (RR = 1.21, 95% CI = 1.01–1.46), diarrhea (RR = 2.62, 95% CI = 1.21–5.65), and anorexia (RR = 2.08, 95% CI = 1.12–3.88) in combining epidermal growth factor receptor targeted therapy group compared to PG group. An increased risk of grade 3 or 4 rash (RR = 5.08, 95% CI = 1.53–16.79), thrombocytopenia (RR = 1.50, 95% CI = 1.03–2.18), and hypertension (RR = 2.36, 95% CI = 1.05–5.32) was observed in sorafenib combination group. Conclusion: The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy. PMID:27977596

  1. Investigation of ternary and quaternary high-temperature fixed-point cells, based on platinum-carbon-X, as blind comparison artefacts

    Science.gov (United States)

    Dong, W.; Machin, G.; Bloembergen, P.; Lowe, D.; Wang, T.

    2016-11-01

    Extensive studies of platinum-carbon eutectic alloy based high temperature fixed point cells have shown that this alloy has extremely good metrological potential as a temperature reference. However, it’s possible adoption as an accepted reference standard means that its eutectic temperature value will soon be agreed with an uncertainty less than most radiation thermometry scales at that temperature. Thus it will lack credibility if used as a future scale comparison artefact. To avoid this, the fixed-point cell can be deliberately doped with an impurity to change its transition temperature by an amount sufficient to test the accuracy of the scales of the institutes, involved in the comparison. In this study dopants of palladium and iridium were added to platinum-carbon to produce ternary alloy and quaternary alloy fixed-point cells. The stability of these artefacts was demonstrated and the fixed-point cells were used to compare the ITS-90 scales of NIM and NPL. It was found that the fixed point temperatures could be changed by an appreciable amount while retaining the stability and repeatability required for comparison artefacts.

  2. Restricted rotation of σ-bonds through a rigidified donor structure to increase the ICT ability of platinum-acetylide-based DSSCs.

    Science.gov (United States)

    Li, Zhong-Yu; Wu, Wenjun; Zhang, Qiong; Jin, Bin; Hua, Jianli; Yang, Hai-Bo; Tian, He

    2013-11-01

    A series of new triarylamine-based platinum-acetylide complexes (WYs) have been designed and synthesized as new sensitizers for applications in dye-sensitized solar cells (DSSCs). With the aim of investigating the effect of a rigidifying donor structure on the photoelectrical parameters of the corresponding DSSCs, two new sensitizers, WY1 and WY2, with rigid and coplanar fluorene units as an electron donor, were prepared. Moreover, two sensitizers that contained triphenylamine units as an electron donor, WY3 and WY4, were also synthesized for comparison. The photo- and electrochemical properties of all of these new complexes have been extensively explored. We found that the dimethyl-fluorene unit exhibited a stronger electron-donating ability and better photovoltaic performance compared to the triphenylamine unit, owing to its rigidifying structure, which restricted the rotation of σ bonds, thus increasing the conjugation efficiency. Furthermore, WY2, which contained a dimethyl-fluorene unit as an electron donor and bithiophene as a π bridge, showed a relatively high open-circuit voltage (V(oc)) of 640 mV and a PCE of 4.09%. This work has not only expanded the choice of platinum-acetylide sensitizers, but also demonstrates the advantages of restricted rotation of donor σ bonds for improved behavior of the corresponding DSSCs.

  3. Synthesis and evaluation of folate-based chlorambucil delivery systems for tumor-targeted chemotherapy.

    Science.gov (United States)

    Guaragna, Annalisa; Chiaviello, Angela; Paolella, Concetta; D'Alonzo, Daniele; Palumbo, Giuseppe; Palumbo, Giovanni

    2012-01-18

    The development of tumor-targeting drug delivery systems, able to selectively transport cytotoxic agents into the tumor site by exploiting subtle morphological and physiological differences between healthy and malignant cells, currently stands as one of the most attractive anticancer strategies used to overcome the selectivity problems of conventional chemotherapy. Owing to frequent overexpression of folate receptors (FRs) on the surface of malignant cells, conjugation of cytotoxic agents to folic acid (FA) via suitable linkers have demonstrated to enhance selective drug delivery to the tumor site. Herein, the chemical synthesis and biological evaluation of two novel folate-conjugates bearing the anticancer agent chlorambucil (CLB) tethered to either an aminoether (4,7,10-trioxa-1,13-tridecanediamine) or a pseudo-β-dipeptide (β-Ala-ED-β-Ala) linker is reported. The two drug delivery systems have been prepared in high overall yields (54% and 34%) through straightforward and versatile synthetic routes. Evaluation of cell specificity was examined using three leukemic cell lines, undifferentiated U937 (not overexpressing FRs, FR(-)), TPA-differentiated U937 (overexpressing FRs, FR(+)), and TK6 (FR(+)) cells. Both conjugates exhibited high specificity only to FR(+) cells (particularly TK6), demonstrating comparable antitumor activity to CLB in its free form. These data confirm the reliability of folate-based drug delivery systems for targeted antitumor therapy; likewise, they lay the foundations for the development of other folate-conjugates with antitumor potential.

  4. The concept of platinum sensitivity could be applied to recurrent cervical cancer: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

    Science.gov (United States)

    Takekuma, Munetaka; Mori, Keita; Iida, Tetsuji; Kurihara, Kazuko; Saitou, Motoaki; Tokunaga, Hideki; Kawana, Kei; Ikeda, Masae; Satoh, Toyomi; Saito, Toshiaki; Miyagi, Etsuko; Nagai, Yutaka; Furusawa, Akiko; Kawano, Yoshiaki; Kawano, Kouichiro; Tabata, Tsutomu; Ota, Yukinobu; Hayase, Ryoji; Mikami, Mikio; Sugiyama, Toru

    2017-08-07

    This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer. The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed. A total of 677 patients from 71 medical centers were analyzed. The median overall survival (OS) for patients with platinum-free interval (PFI) of <6, 6-11, 12-17, and ≥18 months was 12.1 (95% CI 11.0-14.1) months, 17.4 (15.5-20.4) months, 20.2 (17.9-27.6) months, and 29.9 (26.7-36.0) months, respectively (P < 0.0001, log-rank). The best cut-off value of PFI that affected OS was 7 months, analyzed by the minimum P value method. The median progression-free survival (PFS) for patients with less than and more than PFI of 7 months was 6.2 months (95% CI 4.8-9.3) and 21.0 months (18.9-24.8) (P < 0.0001, log-rank), respectively, and the median OS for patients with less than and more than PFI of 7 months was 12.3 months (11.2-14.1) and 24.2 months (20.8-25.8) (P < 0.0001, log-rank). Multivariate analysis revealed that PFI (P < 0.0001, HR 0.449, 95% CI 0.369-0.548) alone had a statistically significant association with OS. This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

  5. Dual-drug delivery of curcumin and platinum drugs in polymeric micelles enhances the synergistic effects: a double act for the treatment of multidrug-resistant cancer.

    Science.gov (United States)

    Scarano, Wei; de Souza, Paul; Stenzel, Martina H

    2015-01-01

    Combinational chemotherapy is often used to prevent drug induced resistance in cancer. The aim of this work is to test whether the co-delivery of drugs within one nanoparticle can result in increased synergistic effects of both drugs. Therefore, a micelle system with two different compartments, one for the drug curcumin and one for the conjugation of platinum drugs was designed. A triblock copolymer, based on the biodegradable polycaprolactone PCL, a PEG based shell and an amine bearing polymer as the interphase for the conjugation of platinum drugs was prepared by combination of ring-opening polymerization and RAFT polymerization. Curcumin was incorporated into the self-assembled onion-type micelle by physical encapsulation into the PCL core with an entrapment capacity of 6 wt%. The platinum(iv) drug oxoplatin was reacted with succinic anhydride to yield Pt(NH3)2Cl2[(COOH)2], which acted as the drug and as a crosslinker for the stabilisation of micelles. The size of the dual drug micelles was measured to be 38 nm by DLS, which was confirmed by TEM. The toxicity of the dual drug delivery system was tested against the A2780 human ovarian cancer cell line and compared with the IC50 value of micelles that deliver either curcumin or the platinum drug alone. The results were analysed using the CalcuSyn software. While curcumin and the platinum drug together without a carrier already showed synergy with a combination index ranging from 0.4 to 0.8, the combined delivery in one nanoparticle did enhance the synergistic effects resulting in a combination index of approximately 0.2-0.35. For comparison, a mixture of two nanoparticles, one with curcumin and the other with the platinum drug, was tested revealing a less noticeable synergistic effect compared to the co-delivery of both drugs in one drug carrier.

  6. Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.

    Science.gov (United States)

    Pietrantonio, Filippo; Mazzaferro, Vincenzo; Miceli, Rosalba; Cotsoglou, Christian; Melotti, Flavia; Fanetti, Giuseppe; Perrone, Federica; Biondani, Pamela; Muscarà, Cecilia; Di Bartolomeo, Maria; Coppa, Jorgelina; Maggi, Claudia; Milione, Massimo; Tamborini, Elena; de Braud, Filippo

    2015-07-01

    Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.

  7. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  8. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  9. Preparation and Characterization of Atactic Poly(vinyl alcohol)/Platinum Nanocomposites by Electrospinning

    Science.gov (United States)

    Seok Lyoo, Won; Jae Lee, Young; Wook Cha, Jin; Jae Kim, Min; Woo Joo, Sang; Soon Gal, Yeong; Hwan Oh, Tae; Soo Han, Sung

    2010-06-01

    Poly(vinyl alcohol) (PVA)/platinum composite nanofibers were successfully prepared by the electrospinning method. Water-based colloidal platinum in a PVA solution was directly mixed without any chemical or structural modifications into PVA polymer fibers to form organic-inorganic composite nanofibers. The PVA/platinum composite nanofibers were characterized by field emission scanning electron microscopy (SEM).

  10. SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    Full Text Available AIM: The role of Sirtuin 1 (SIRT 1 in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC. METHODS: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS and progression free survival (PFS. In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA. The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice. RESULTS: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice. CONCLUSION: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

  11. DNA修复率与晚期消化道肿瘤含铂化疗方案疗效相关性的研究%Correlation between DNA repair rates and platinum-containing chemotherapy efficacy for patients with ad-vanced gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    王丹丹; 顾康生

    2015-01-01

    Objective To investigate the relationship between the DNA repair rate( DRR) of peripheral blood lymphocytes ( PBLC) and platinum⁃containing chemotherapy efficacy in advanced gastrointestinal malignancies. Methods The DRR of PBLC from 112 patients with advanced gastrointestinal cancer patients( cancer group) were detected by single cell gel electrophoresis( SCGE) , and other 60 patients with healthy subjects were selected as controls( control group) . Cancer patients were treated in parallel platinum⁃con⁃taining chemotherapy regimens to evaluate the short⁃term effect. In cancer group, the DRR of the two platinum groups before and after exposure to platinum were analyzed. Then, the correlation between the DRR of cancer group and clinical pathological features and effi⁃cacy of chemotherapy regimens containing platinum was also investigated. Results Tail length( TL) and tail moment( TM) were uti⁃lized to detect the DRR of esophageal cancer(Z=-4�687, P=0�000; Z=-4�939, P=0�000), gastric cancer(Z=-5�473, P=0�000;Z=-3�789, P=0�000) and colorectal cancer( Z=-5�796, P=0�000;Z=-5�206, P=0�000) . The PBLC DRRs of cancer group were lower than that of control group counterpart. The PBLC DRR of cancer group exhibit no correlation to sex, age, ECOG score, alcohol habits and tissue differentiation of the tumor( P>0�05) . Among 112 patients, 110 cases were evaluable for efficacy. For esophageal cancer, there were 3 cases of PR, 6 cases of SD and 12 cases of PD with response rate( RR) of 14�3% and disease control rate( DCR) of 42�9%. For gastric cancer, there were 1 case of CR, 5 cases of PR, 10 cases of SD and 20 cases of PD with RR of 16�7% and DCR of 44�4%. For colorectal cancer, there were 2 cases of CR, 8 cases of PR, 13 cases of SD and 30 cases of PD with RR of 18�9% and DCR of 43�4%.When TL was utilized as an evaluation index of DRR, the DRR of esophageal cancer(r=-0�500, P=0�021), gastric cancer(r=-0�546, P=0�001

  12. Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

    2015-12-01

    The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10-17) and 31 (28-36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13-22) and an OS of 38 (33-41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20-0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95-9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may

  13. Chemotherapy-related thrombocytosis: does it increase the risk of thromboembolism?.

    Science.gov (United States)

    Ahmed, S; Shahid, R K; Bhatt, H; Lee-Ying, R; Lim, J

    2012-01-01

    Chemotherapy increases the risk of thromboembolism in patients with cancer. Although thrombocytopenia is a known side effect of chemotherapy, reactive thrombocytosis related to chemotherapy is uncommonly reported. The present study aimed to determine the incidence of gemcitabine-related thrombocytosis and the associated risk of thromboembolism. Medical records of 250 consecutive patients with a malignant disease who received gemcitabine-based therapy were reviewed. A multivariate analysis was done to determine factors associated with thromboembolism. A total of 220 eligible patients with a median age of 63 years (range 26-83) were identified. Of these 220 patients, 95% had advanced malignancy and 59% had received prior chemotherapy. A total of 69% of patients received a platinum combination. In all, 46% patients experienced thrombocytosis following chemotherapy, with a median platelet count of 632 × 10(9)/l (range 457-1,385). Twenty-three of the 220 patients experienced a vascular event within 6 weeks of treatment. Eleven patients with thrombocytosis experienced a vascular event compared with 10 patients without thrombocytosis (not significant). On multivariate analysis, leukocytosis (odds ratio 5.8, 95% confidence interval 2.1-15.8) and comorbid illnesses (odds ratio 4.1, 95% confidence interval 1.4-12.6) were correlated with thromboembolism. Although gemcitabine-based therapy has been associated with an increased incidence of thrombocytosis, it does not increase the risk of thromboembolism in cancer patients. Leukocytosis and comorbid illnesses do increase the risk of thromboembolism. Copyright © 2012 S. Karger AG, Basel.

  14. Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

    Science.gov (United States)

    Hervault, Aziliz; Thanh, Nguyen Th Kim

    2014-10-21

    Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

  15. Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Hsueh-Ju Lu

    2015-01-01

    Full Text Available Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC. We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0 months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%. Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%. No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC.

  16. A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases.

    Science.gov (United States)

    Kasparkova, Jana; Kostrhunova, Hana; Novakova, Olga; Křikavová, Radka; Vančo, Ján; Trávníček, Zdeněk; Brabec, Viktor

    2015-11-23

    We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl-bis-hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a Pt(IV) pro-drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy.

  17. Feasibility, toxicity, and efficacy of short induction chemotherapy of docetaxel plus cisplatin or carboplatin (TP) followed by concurrent chemoradiotherapy for organ preservation in advanced cancer of the hypopharynx, larynx, and base of tongue. Early results

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Sabine; Klautke, Gunther; Fietkau, Rainer [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Waldfahrer, Frank; Iro, Heinrich [Erlangen-Nuernberg Univ., Erlangen (Germany). Hals-Nasen-Ohrenklinik, Kopf- und Halschirurgie; Lell, Michael; Uder, Michael [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Radiologie; Linke, Rainer; Kuwert, Torsten [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. und Poliklinik fuer Nuklearmedizin

    2011-01-15

    Concurrent chemoradiotherapy (CRT) is standard treatment for advanced head and neck cancer. Whether short induction chemotherapy (ICT) provides additional benefit or, in particular, predictive benefit for the response to chemoradiotherapy is an open question. The present study aimed to assess the feasibility, toxicity, and efficacy of induction with docetaxel and platinum salt (TP) and subsequent CRT. A total of 25 patients with functionally inoperable cancer of the base of the tongue, hypopharynx, or larynx received 1 cycle of docetaxel (75 mg/m{sup 2}, day 1) combined with either cisplatin (30 mg/m{sup 2}, days 1-3; n = 23) or carboplatin (AUC 1.5 days 1-3; n = 2). Responders (n = 22, > 30% tumor reduction, graded by endoscopy) and 1 non-responder received CRT (target dose: 69-72 Gy) with cisplatin/paclitaxel, carboplatin/paclitaxel, or cisplatin/docetaxel. All patients completed ICT with acceptable toxicity (leukocytopenia grade 4: 8%). The remission rate of the primary tumor was 88% (22/25 patients). There was no need to delay CRT due to toxicity in any case. Each patient received the full radiation dose. Of the patients, 56% received > 80% of the chemotherapy. The acute toxicity of CRT was moderate, no grade 4 toxicities occurred, while grade 3 toxicities included the following: infection (39%), dermatitis (13%), leukocytopenia (30%), and thrombocytopenia (4%). The local control rate was 84.6% {+-} 8.5% and the survival rate was 89.6% {+-} 7.2% at 12 months. Organ preservation was possible in 22/23 (95%) cases. Short induction with a TP regimen and subsequent CRT with a taxan is feasible and associated with an encouraging local control rate. (orig.)

  18. A Comparison of Contemporary Gold Versus Platinum Thermocouples with NIST SRM 1749-Based Thermocouples and Reference Function

    Science.gov (United States)

    Coleman, M. J.; Wiandt, T. J.; Harper, T.

    2015-12-01

    Fluke Calibration (formerly Hart Scientific) in American Fork, Utah, USA is a manufacturer of temperature calibration instruments. The company manufactured reference standard gold versus platinum (Au-Pt) thermocouples from 1992 to about 2002. Manufacturing was halted in 2002 because a trend of poor curve-fit results was observed in new batches of wire. After reviewing the possible sources of the problem, it was decided to sample wire from multiple manufacturers and investigate ways to make the curve-fit work better. This paper presents the results from the study of the wire and a characterization technique to help improve characterization of thermocouples made with lower purity wire. Calibration results from NIST SRM material and older Fluke thermocouples are included as well to provide a means of comparison of contemporary wire to NIST SRM era wire.

  19. Oxygen Reduction on Platinum

    DEFF Research Database (Denmark)

    Nesselberger, Markus

    This thesis investigates the electro reduction of oxygen on platinum nanoparticles, which serve as catalyst in low temperature fuel cells. Kinetic studies on model catalysts as well as commercially used systems are presented in order to investigate the particle size effect, the particle proximity...... carbon (HSAC) supported Pt nanoparticle (Pt/C) catalysts (of various size between 1 and 5 nm). The difference in SA between the individual Pt/C catalysts (1 to 5 nm) is very small and within the error of the measurements. The factor four of loss in SA when comparing platinum bulk and Pt/C can largely...

  20. Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations.

    Science.gov (United States)

    Britto, Constança Carvalho

    2009-07-01

    One major goal of research on Chagas disease is the development of effective chemotherapy to eliminate the infection from individuals who have not yet developed cardiac and/or digestive disease manifestations. Cure evaluation is the more complex aspect of its treatment, often leading to diverse and controversial results. The absence of reliable methods or a diagnostic gold standard to assess etiologic treatment efficacy still constitutes a major challenge. In an effort to develop more sensitive tools, polymerase chain reaction (PCR)-based assays were introduced to detect low amounts of Trypanosoma cruzi DNA in blood samples from chagasic patients, thus improving the diagnosis and follow-up evaluation after chemotherapy. In this article, I review the main problems concerning drug efficacy and criteria used for cure estimation in treated chagasic patients, and the work conducted by different groups on developing PCR methodologies to monitor treatment outcome of congenital infections as well as recent and late chronic T. cruzi infections.

  1. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

    Directory of Open Access Journals (Sweden)

    Serpe L

    2014-01-01

    Full Text Available Loredana Serpe, Margherita Gallicchio, Roberto Canaparo, Franco DosioDepartment of Drug Science and Technology, University of Turin, ItalyAbstract: Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.Keywords: vintafolide, etarfolatide, platinum-resistant ovarian cancer, targeted therapy, biomarkers, folate receptor

  2. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Willemse, Peter-Paul M; van der Meer, Rutger W; Burggraaf, Jacobus; van Elderen, Saskia G C; de Kam, Marieke L; de Roos, Albert; Lamb, Hildo J; Osanto, Susanne

    2014-03-01

    Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m(2) (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development

  3. Psychoneuroimmunology-Based Stress Management during Adjuvant Chemotherapy for Early Breast Cancer.

    Science.gov (United States)

    Robins, Jo Lynne W; McCain, Nancy L; Elswick, R K; Walter, Jeanne M; Gray, D Patricia; Tuck, Inez

    2013-01-01

    Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL), and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27-75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL and psychosocial functioning, normalize levels of stress-related neuroendocrine mediators, and attenuate immunosuppression. Results. While interesting patterns were seen across the sample and over time, the interventions had no appreciable effects when delivered during the period of chemotherapy. Conclusions. Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes. Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period. It may be that interventions requiring less activity and/or group attendance would have enhanced therapeutic effects, and more active interventions need to be tested prior to and following recovery from chemotherapy.

  4. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer

    OpenAIRE

    Rubbia-Brandt, Laura; Audard, V; Sartoretti, Pascal Daniel; Roth, Arnaud; Brezault, C; Le Charpentier, M; Dousset, B.; Morel, Philippe; O. Soubrane; Chaussade, S; Mentha, Gilles; Terris, B

    2004-01-01

    In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver.

  5. Psychoneuroimmunology-Based Stress Management during Adjuvant Chemotherapy for Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jo Lynne W. Robins

    2013-01-01

    Full Text Available Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL, and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27–75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL and psychosocial functioning, normalize levels of stress-related neuroendocrine mediators, and attenuate immunosuppression. Results. While interesting patterns were seen across the sample and over time, the interventions had no appreciable effects when delivered during the period of chemotherapy. Conclusions. Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes. Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period. It may be that interventions requiring less activity and/or group attendance would have enhanced therapeutic effects, and more active interventions need to be tested prior to and following recovery from chemotherapy.

  6. Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics.

    Science.gov (United States)

    Ahmad, Javed; Amin, Saima; Rahman, Mahfoozur; Rub, Rehan Abdur; Singhal, Madhur; Ahmad, Mohammad Zaki; Rahman, Ziyaur; Addo, Richard T; Ahmad, Farhan Jalees; Mushtaq, Gohar; Kamal, Mohammad Amjad; Akhter, Sohail

    2015-01-01

    Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed.

  7. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

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    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  8. 紫杉醇和铂剂联合治疗NSCLC的临床研究%A randomized phase Ⅱ trial of paclitaxel in combination chemotherapy with platinum in the treatment of non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    严德钧; 王国忠; 张高兆; 胡驰雄

    2001-01-01

    目的 比较紫杉醇-卡铂(TAX-CBP)方案和紫杉醇-顺铂(TAX-DDP)方案治疗非小细胞肺癌(NSCLC)的疗效。方法 126例NSCLC病例被随机分入TAX-CBP组和TAX-DDP组。TAX-CBP方案:TAX 175*!mg/m2静脉滴注第1天,CBP 350*!mg/m2静脉滴注第1天。TAX-DDP方案:TAX 175*!mg/m2静脉滴注第1天,DDP 100*!mg/m2静脉滴注第1天(需水化)。28天为一周期,对连续使用三个周期者进行疗效评估。结果 TAX-CBP组化疗有效率为36%(22/61),1年生存率为34.1%,TAX-DDP组化疗有效率为33.9%(21/62),1年生存率为33.1%,二组疗效无显著性差异(P>0.05),但中位生存期TAX-CBP组(11.2个月)优于TAX-DDP组(9个月)(P<0.05)。副作用依次为脱发、骨髓抑制、胃肠道反应和肌肉(关节)疼痛。TAX-CBP组血小板减少发生率显著高于TAX-DDP组(P<0.05),而TAX-DDP组消化道反应、肌肉(关节)痛发生率显著高于TAX-CBP组(P<0.05)。结论 TAX-CBP方案和TAX-CDDP方案均可作为NSCLC的一线化疗方案。%Objective To compare the efficacy and toxicity of paclitaxel-carboplatin (TAX-CBP) and paclitaxel-cisplatin (TAX-DDP) chemotherapy protocols for advanced non-small cell lung cancer. Methods One hundred and twenty-six patients with non-small cell lung cancer were randomized into TAX-DDP and TAX-CBP groups. TAX-CBP group: TAX 175*!mg/m2 and CBP 350*!mg/m2, d1 iv; TAX-DDP group: TAX 175*!mg/m2 and DDP 100*!mg/m2 d1 iv. The therapy was repeated every 28 days. The response rate was assessed after three treatments. Results TAX-CBP group: response rate (RR) was 36% (22/61), 1-year survival rate was 34.1%. TAX-DDP group: RR was 33.9% (21/62),1-year survival rate was 33.1%. There was no significant difference of RR and 1-year survival rate between TAX-CBP and TAX-DDP group (P>0.05). The median survival time of TAX-CBP group (11.2 months) was significant higher

  9. Low-Dose Whole Brain Radiotherapy with Tumor Bed Boost after Methotrexate-Based Chemotherapy for Primary Central Nervous System Lymphoma

    OpenAIRE

    Kim, Byoung Hyuck; Kim, Il Han; Park, Sung-Hye; Park, Chul Kee; Jung, Hee Won; Kim, Tae Min; Lee, Se-Hoon; Heo, Dae Seog

    2014-01-01

    Purpose The purpose of this study is to evaluate the outcome of low-dose whole brain radiotherapy (WBRT) with tumor bed boost after methotrexate-based chemotherapy in the management of primary central nervous system lymphoma (PCNSL). Materials and Methods We retrospectively analyzed 64 patients with pathologically proven PCNSL between 2000 and 2011. Methotrexate-based chemotherapy with a median of five cycles was followed by radiotherapy to the whole brain and to the initial tumor bed. The me...

  10. Neurotoxicity Caused by the Treatment with Platinum Analogues

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    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  11. Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Khaleel R Fareed; Irshad N Soomro; Khalid Hameed; Arvind Arora; Dileep N Lobo; Simon L Parsons; Srinivasan Madhusudan

    2012-01-01

    AIM:To examine cytokeratin-18 (CK-18) and caspasecleaved CK-18 expression in tumouts and correlate with clinicopathological outcomes including tumour regression grade (TRG) response.METHODS:Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays.The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastrooesophageal cancer cases exposed to pre-operative platinum-based chemotherapy.Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.RESULTS:CK18 was commonly expressed in gastrooesophageal tumours (92.6%).Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy (P =0.009).In patients who received neoadjuvant chemotherapy,caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response (TRG 1,2 or 3,P =0.043).CONCLUSION:This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastrooesophageal tumours.We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant chemotherapy.

  12. Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab.

    Science.gov (United States)

    Kim, In-Ho; Lee, Ji Eun; Youn, Ho-Joong; Song, Byung Joo; Chae, Byung Joo

    2017-03-01

    We intended to determine whether dexrazoxane (DZR) is cardioprotective during administration of adjuvant anthracycline-based chemotherapy followed by a 1-year trastuzumab treatment. The medical records of 228 patients who underwent surgical resection and received adjuvant chemotherapy with trastuzumab for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer between January 2010 and December 2014 were reviewed. Approximately 25% of patients received DZR prior to each administration of doxorubicin during doxorubicin with cyclophosphamide (AC) chemotherapy. DZR was not administered during the 1-year trastuzumab maintenance period. Rates of cardiac events (reduction in left ventricular ejection fraction [LVEF] by 10% or more; reduction in absolute LVEF to effect of time, and a significant group (DZR)×time interaction. The group treated with adjuvant chemotherapy and DZR experienced significantly lower frequencies of cardiac events than the adjuvant chemotherapy only group. In multivariate analysis, DZR administration was associated with significantly fewer cardiac events. Moreover, DZR administration was an independent good prognostic factor for CFD. Only one patient (2.3%) experienced early interruption of trastuzumab in the adjuvant chemotherapy with DZR group due to cardiac toxicity, whereas 10 patients (7.6%) experienced a trastuzumab stop event in the adjuvant chemotherapy only group. DZR is cardioprotective in HER2-positive breast cancer patients who received adjuvant chemotherapy with trastuzumab. A large cohort randomized trial is needed to determine if DZR has an effect on trastuzumab interruption and completion of 12-month trastuzumab. Because cardiac toxicity has a significant negative effect on trastuzumab maintenance and quality of life, DZR administration could be considered concomitantly with anthracycline-based adjuvant chemotherapy with trastuzumab.

  13. Effect of chemotherapy on health-related quality of life among early-stage ovarian cancer survivors: a study from the population-based PROFILES registry

    Science.gov (United States)

    Bhugwandass, C.S.; Pijnenborg, J.M.A.; Pijlman, B.; Ezendam, N.P.M.

    2016-01-01

    Background There is wide variation in the application of adjuvant chemotherapy in early-stage epithelial ovarian cancer. Our aim was to assess differences in health-related quality of life (hrqol) between patients with early-stage ovarian cancer who did or did not receive chemotherapy as adjuvant treatment. Methods All patients diagnosed with early-stage ovarian cancer between 2000 and 2010 within the population-based Eindhoven Cancer Registry (n = 191) were enrolled in this study. Patients were requested to complete questionnaires, including the cancer-specific (qlq-C30) and ovarian cancer-specific (qlq-OV28) quality of life measures from the European Organisation for Research and Treatment of Cancer. Primary outcome measures were the generic-and cancer-specific domain scores for hrqol in ovarian cancer survivors. Results Of the 107 patients (56%) who returned the questionnaires, 57 (53.3%) had received adjuvant chemotherapy and 50 (46.7%) had been treated with surgery alone. Significant differences in hrqol between those groups were found in the symptom scales for peripheral neuropathy, attitude toward sickness, and financial situation, with worse scores in the chemotherapy group. Conclusions Results of our study show that patients who receive adjuvant chemotherapy have a significantly worse score for 3 aspects of hrqol. Efforts should be made to reduce use of adjuvant chemotherapy in early-stage ovarian cancer. Moreover, preventive strategies to improve long-term quality of life for those who need adjuvant chemotherapy should be explored. PMID:28050144

  14. DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1

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    Connor Joseph P

    2012-05-01

    Full Text Available Abstract Background Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC. In our previous work Decoy Receptor 3 (DcR3 was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness. Methods We studied cell lines and primary cultures for the expression of and the cells ability to bind DcR3. Cells were cultured with DcR3 and then exposed to platinum. Cell viability was determined by MTT assay. Finally, the cells molecular response to DcR3 was studied using real time RT-PCR based differential expression arrays, standard RT-PCR, and Western blot. Results High DcR3 in the peritoneal cavity of women with EOC is associated with significantly shorter time to first recurrence after platinum based therapy (p = 0.02. None-malignant cells contribute DcR3 in the peritoneal cavity. The cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to their surface implying that they can be effected by DcR3 from other sources. DcR3s protein binding partners are minimally expressed or negative, however, all cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs Syndecans-2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3 exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more cells surviving at high doses. On the contrary CaOV3 became more sensitive to platinum with 20–25% more cell death. PCR array analysis showed increase expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR and Western blot analysis. Conclusions Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy. The

  15. Platinum Complexes And Their Anti-Tumour Activity Against Chronic Lymphocytic Leukaemia Cells

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    Silconi Žana Besser

    2015-09-01

    Full Text Available Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum-based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity, ototoxicity, and neurotoxicity. Although cisplatin is one of the most successful anticancer drugs to date, its biochemical mechanism of action is still unclear. Cisplatin is generally accepted as having the ability to interact with the purine bases on the DNA, causing DNA damage, interfering with DNA repair mechanisms, and subsequently inducing apoptosis in cancer cells.

  16. [Icteric hepatitis in a patient with non-Hodgkin's lymphoma treated by rituximab-based chemotherapy].

    Science.gov (United States)

    Coppola, Nicola; Masiello, Addolorata; Tonziello, Gilda; Macera, Margherita; Iodice, Valentina; Caprio, Nunzio; Pasquale, Giuseppe

    2010-06-01

    We report the case of a patient with non-Hodgkin's lymphoma who, during chemotherapy according to the r-CHOP schedule (rituximab-cyclophosphamide-doxorubicin-vincristine and prednisone), showed a hepatic flare with jaundice. Given the patient's state of asymptomatic carrier of HBsAg, we began a treatment of telbivudine (600 mg/die), resulting in a regression of hepatitis flare and negativization of HBV viraemia.

  17. Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy

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    Aebi Stefan

    2008-10-01

    Full Text Available Abstract Background The activity of dihydropyrimidine dehydrogenase (DPD, the key enzyme of pyrimidine catabolism, is thought to be an important determinant for the occurrence of severe toxic reactions to 5-fluorouracil (5-FU, which is one of the most commonly prescribed chemotherapeutic agents for the treatment of solid cancers. Genetic variation in the DPD gene (DPYD has been proposed as a main factor for variation in DPD activity in the population. However, only a small proportion of severe toxicities in 5-FU based chemotherapy can be explained with such rare deleterious DPYD mutations resulting in severe enzyme deficiencies. Recently, hypermethylation of the DPYD promoter region has been proposed as an alternative mechanism for DPD deficiency and thus as a major cause of severe 5-FU toxicity. Methods Here, the prognostic significance of this epigenetic marker with respect to severe 5-FU toxicity was assessed in 27 cancer patients receiving 5-FU based chemotherapy, including 17 patients experiencing severe toxic side effects following drug administration, none of which were carriers of a known deleterious DPYD mutation, and ten control patients. The methylation status of the DPYD promoter region in peripheral blood mononuclear cells was evaluated by analysing for each patient between 19 and 30 different clones of a PCR-amplified 209 base pair fragment of the bisulfite-modified DPYD promoter region. The fragments were sequenced to detect bisulfite-induced, methylation-dependent sequence differences. Results No evidence of DPYD promoter methylation was observed in any of the investigated patient samples, whereas in a control experiment, as little as 10% methylated genomic DNA could be detected. Conclusion Our results indicate that DYPD promoter hypermethylation is not of major importance as a prognostic factor for severe toxicity in 5-FU based chemotherapy.

  18. Fabrication of Nano-Crossbar Resistive Switching Memory Based on the Copper-Tantalum Pentoxide-Platinum Device Structure

    Science.gov (United States)

    Olga Gneri, Paula; Jardim, Marcos

    Resistive switching memory has been of interest lately not only for its simple metal-insulator-metal (MIM) structure but also for its promising ease of scalability an integration into current CMOS technologies like the Field Programmable Gate Arrays and other non-volatile memory applications. There are several resistive switching MIM combinations but under this scope of research, attention will be paid to the bipolar resistive switching characteristics and fabrication of Tantalum Pentaoxide sandwiched between platinum and copper. By changing the polarity of the voltage bias, this metal-insulator-metal (MIM) device can be switched between a high resistive state (OFF) and low resistive state (ON). The change in states is induced by an electrochemical metallization process, which causes a formation or dissolution of Cu metal filamentary paths in the Tantalum Pentaoxide insulator. There is very little thorough experimental information about the Cu-Ta 2O5-Pt switching characteristics when scaled to nanometer dimensions. In this light, the MIM structure was fabricated in a two-dimensional crossbar format. Also, with the limited available resources, a multi-spacer technique was formulated to localize the active device area in this MIM configuration to less than 20nm. This step is important in understanding the switching characteristics and reliability of this structure when scaled to nanometer dimensions.

  19. Flanking bases influence the nature of DNA distortion by platinum 1,2-intrastrand (GG cross-links.

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    Debadeep Bhattacharyya

    Full Text Available The differences in efficacy and molecular mechanisms of platinum anti-cancer drugs cisplatin (CP and oxaliplatin (OX are thought to be partially due to the differences in the DNA conformations of the CP and OX adducts that form on adjacent guanines on DNA, which in turn influence the binding of damage-recognition proteins that control downstream effects of the adducts. Here we report a comprehensive comparison of the structural distortion of DNA caused by CP and OX adducts in the TGGT sequence context using nuclear magnetic resonance (NMR spectroscopy and molecular dynamics (MD simulations. When compared to our previous studies in other sequence contexts, these structural studies help us understand the effect of the sequence context on the conformation of Pt-GG DNA adducts. We find that both the sequence context and the type of Pt-GG DNA adduct (CP vs. OX play an important role in the conformation and the conformational dynamics of Pt-DNA adducts, possibly explaining their influence on the ability of many damage-recognition proteins to bind to Pt-DNA adducts.

  20. Copolymers Based on Indole-6-Carboxylic Acid and 3,4-Ethylenedioxythiophene as Platinum Catalyst Support for Methanol Oxidation

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    Tzi-Yi Wu

    2015-10-01

    Full Text Available Indole-6-carboxylic acid (ICA and 3,4-ethylenedioxythiophene (EDOT are copolymerized electrochemically on a stainless steel (SS electrode to obtain poly(indole-6-carboxylic acid-co-3,4-ethylenedioxythiophenes (P(ICA-co-EDOTs. The morphology of P(ICA-co-EDOTs is checked using scanning electron microscopy (SEM, and the SEM images reveal that these films are composed of highly porous fibers when the feed molar ratio of ICA/EDOT is greater than 3/2. Platinum particles can be electrochemically deposited into the P(ICA-co-EDOTs and PICA films to obtain P(ICA-co-EDOTs-Pt and PICA-Pt composite electrodes, respectively. These composite electrodes are further characterized using X-ray photoelectron spectroscopy (XPS, SEM, X-ray diffraction analysis (XRD, and cyclic voltammetry (CV. The SEM result indicates that Pt particles disperse more uniformly into the highly porous P(ICA3-co-EDOT2 fibers (feed molar ratio of ICA/EDOT = 3/2. The P(ICA3-co-EDOT2-Pt nanocomposite electrode exhibited excellent catalytic activity for the electrooxidation of methanol in these electrodes, which reveals that P(ICA3-co-EDOT2-Pt nanocomposite electrodes are more promising for application in an electrocatalyst as a support material.

  1. New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: design, synthesis, structure-activity relationships and biological evaluation.

    Science.gov (United States)

    Fortin, Sébastien; Brasseur, Kevin; Morin, Nathalie; Asselin, Éric; Bérubé, Gervais

    2013-10-01

    Prostate cancer is a major public health problem worldwide and, more specifically, new treatments for hormone-refractory cancers are highly sought by several research groups. Although platinum(II)-based chemotherapy and other strategies grow in interest to treat castration-resistant prostate cancer (CRPC), they still exhibit modest activity on CRPC and overall patient survival. In this study, we designed and prepared new combi-molecules using 17β-acetyl-testosterone and amino acid platinum(II) complexes linked at the position 7α to target and to improve the antiproliferative activity of platinum(II)-based chemotherapy on prostate cancer cells. Twelve chemical intermediates and six new combi-molecules were prepared and characterized. Structure-activity relationships studies show that the platinum complex moiety is essential for an optimal cytocidal activity. Moreover, stereochemistry of the amino acid involved in the platinum complexes had only minor effects on the antiproliferative activity whereas pyridinyl (10a and b) and thiazolyl (10f) complexes exhibited the highest cytocidal activities that are significantly superior to that of cisplatin used as control on human prostate adenocarcinoma LNCaP (AR+), PC3 (AR-) and DU145 (AR-). Compounds 10a, b and f arrested the cell cycle progression in S-phase and induced double strand breaks as confirmed by the phosphorylation of histone H2AX into γH2AX. Compounds 10a and f showed 33 and 30% inhibition, respectively of the growth of HT-1080 tumors grafted onto chick chorioallantoic membranes. Finally, compounds 10a and 10f exhibited low toxicity on the chick embryos (18 and 21% of death, respectively), indicating that these new combi-molecules might be a promising new class of anticancer agents for prostate cancer.

  2. Predictive Role of Galectin-1 and Integrin α5β1 in Cisplatin-based Neoadjuvant Chemotherapy of Bulky Squamous Cervical Cancer.

    Science.gov (United States)

    Zhu, Haiyan; Chen, Aixue; Li, Saisai; Tao, Xuejiao; Sheng, Bo; Chetry, Mandika; Zhu, Xueqiong

    2017-08-25

    Although galectin-1 and integrin α5β1 confer chemoresistance in certain types of cancer, whether their expression predicts the response to cisplatin-based neoadjuvant chemotherapy in squamous cervical cancer remains unclear. Paired tumor samples (pre- and post-chemotherapy) were obtained from 35 bulky squamous cervical cancer patients treated with cisplatin-based neoadjuvant chemotherapy and radical hysterectomy at our hospital between January 2007 and August 2014. The expression of galectin-1 and integrin α5β1 in tumor cells and stromal cells was analyzed by immunohistochemistry. The correlation between galectin-1/ integrin α5β1 and apoptosis-associated markers was investigated by using the TCGA RNA-sequencing data. Seventeen patients were identified as chemotherapy-responders and 18 were non-responders. Galectin-1 and integrin α5β1-positive immunostaining was more frequently observed in stromal cells than in tumor cells. The expression of galectin-1 and integrin α5β1 in stromal and tumor cells was significantly down-regulated in post-chemotherapy cervical cancer tissues. High levels of galectin-1 and integrin α5β1 in stromal were associated with a negative chemotherapy response in squamous cervical cancer patients treated with cisplatin-based neoadjuvant chemotherapy. Additional, the expression of galectin-1 and integrin α5 correlated negatively with caspase 3/ caspase 8 by using the TCGA RNA-sequencing data. Galectin-1 and integrin α5β1 expression in stromal may serve as a prediction of the responses to cisplatin-based neoadjuvant chemotherapy for patients with bulky squamous cervical cancer. Galectin-1 and integrin α5β1 may be implicated in the development of chemoresistance in cervical cancer via suppressing apoptosis. ©2017 The Author(s).

  3. Novel platinum(IV) complexes induce rapid tumor cell death in vitro.

    Science.gov (United States)

    Kaludjerović, Goran N; Miljković, Djordje; Momcilović, Miljana; Djinović, Vesna M; Mostarica Stojković, Marija; Sabo, Tibor J; Trajković, Vladimir

    2005-09-01

    The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.

  4. Root bark extracts of Juncus effusus and Paeonia suffruticosa protect salivary gland acinar cells from apoptotic cell death induced by cis-platinum (II) diammine dichloride.

    Science.gov (United States)

    Mukudai, Yoshiki; Kondo, Seiji; Shiogama, Sunao; Koyama, Tomoyuki; Li, Chunnan; Yazawa, Kazunaga; Shintani, Satoru

    2013-12-01

    Cis-platinum (II) diammine dichloride (CDDP) is a platinum-based anticancer agent, and is often used for chemotherapy for malignant tumors, albeit CDDP has serious side-effects, including xerostomia (dry mouth). Since patients with xerostomia have reduced quality of life, it is urgent and important to identify nontoxic and natural agents capable of reducing the adverse effect of chemotherapy on salivary gland function. Therefore, we commenced an institutional collaborative project in which candidates of herbal extracts were selected from more than 400 bioactive herbal products for their potential therapeutic effects not only on xerostomia, but also on oral diseases. In the present study, we report on two Chinese medical herbal extracts from the root barks of Juncus effusus and Paeonia suffruticosa. The two extracts showed a protective effect in NS-SV-Ac cells from the cytotoxicity and apoptosis caused by CDDP. The effect was dependent on the p53 pathway, protein kinase B/Akt 1 and mitochondrial apoptosis-related proteins (i.e. Bcl-2 and Bax), but was not dependent on nuclear factor κB. Notably, the apoptosis-protective effect of the extracts was not observed in adenocystic carcinoma cell lines. Although these extracts have been utilized in traditional Chinese medicine for hundreds of years, there are no reports to our knowledge, on their therapeutic effects on xerostomia. Thus, in the present study, we elucidated the potency of these herbal extracts as novel candidates for xerostomia to improve the quality of life of patients undergoing chemotherapy.

  5. Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

    Directory of Open Access Journals (Sweden)

    Uribe Jesus

    2005-09-01

    Full Text Available Abstract Background Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. Methods Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. Results Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. Conclusion Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.

  6. Chemotherapy-based control of schistosomiasis haematobia. 3. Snail studies monitoring the effect of chemotherapy on transmission in the Msambweni area, Kenya.

    Science.gov (United States)

    Sturrock, R F; Kinyanjui, H; Thíongo, F W; Tosha, S; Ouma, J H; King, C H; Koech, D; Siongok, T K; Mahmoud, A A

    1990-01-01

    Regular snail sampling was performed at 40 sites, representing the principal snail habitats, during a 4 year chemotherapy programme targetted at school-children in the Msambweni area of the coastal plain of Kenya. Populations of Bulinus africanus group snails, primarily from pools, showed seasonal variations, dropping when sites dried out and rising when they were refilled by the rains. Transmission, judged by the recovery of snails shedding typical fucocercous cercariae, continued throughout the treatment period at very low levels (less than 1% of the snails collected were infected) with peaks in October/November and in January/February after seasonal rains. Spatially, most infected snails were recovered from 2 large pools near the sea, close to the school that responded least well to the initial chemotherapy programme. Later, infected snails were found sporadically in inland pools, rice fields and temporary streams near another school where there was evidence of substantial reinfection as the study progressed. The snail findings are consistent with a reduction but not elimination of transmission associated with the chemotherapy programme.

  7. Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps

    Energy Technology Data Exchange (ETDEWEB)

    Castellano, Antonella; Iadanza, Antonella; Falini, Andrea [San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Neuroradiology Unit and CERMAC, Milano (Italy); Donativi, Marina [University of Salento, Department of Mathematics and Physics ' ' Ennio De Giorgi' ' and A.D.A.M. (Advanced Data Analysis in Medicine), Lecce (Italy); Ruda, Roberta; Bertero, Luca; Soffietti, Riccardo [University of Torino, Department of Neuro-oncology, Turin (Italy); De Nunzio, Giorgio [University of Salento, Department of Mathematics and Physics ' ' Ennio De Giorgi' ' and A.D.A.M. (Advanced Data Analysis in Medicine), Lecce (Italy); INFN (National Institute of Nuclear Physics), Lecce (Italy); Riva, Marco; Bello, Lorenzo [Universita degli Studi di Milano, Milan, and Humanitas Research Hospital, Department of Medical Biotechnology and Translational Medicine, Rozzano, MI (Italy); Rucco, Matteo [University of Camerino, School of Science and Technology, Computer Science Division, Camerino, MC (Italy)

    2016-05-15

    To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy. Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b = 1000 s/mm{sup 2}, 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response. After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P ≤ 0.03). After six cycles, DTI changes were more pronounced (P ≤ 0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R{sup 2} = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs. DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients. (orig.)

  8. Novel platinum(IV) complexes conjugated with a wogonin derivative as multi-targeted anticancer agents.

    Science.gov (United States)

    Qin, Xiaodong; Xu, Gang; Chen, Feihong; Fang, Lei; Gou, Shaohua

    2017-04-15

    Platinum-based complexes like cisplatin and oxaliplatin are well known the mainstay of chemotherapy regimens on clinic. Wogonin, a natural product that possesses wide biological activities, is now in phase I clinical test as an anticancer agent in China. Herein reported are a series of novel Pt(IV) complexes that conjugated a wogonin derivative (compound 3) to the axial position via a linker group. After being tethered to the platinum(IV) complexes, the wogonin derivative provided multiple anticancer effects, especially in compound 10, a fusion containing wogonin and cisplatin units. Compound 10 not only inherited the genotoxicity from cisplatin, but also obtained the COX inhibitory property from the wogonin derivative. Further mechanistic investigation revealed that compound 10 caused the accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and then activated the p53 pathway. Overall, the research demonstrates that the "integrative" prodrug can be an effective strategy to promote the anticancer potency of Pt-based drugs for cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer.

    Science.gov (United States)

    Azzoli, Christopher G; Baker, Sherman; Temin, Sarah; Pao, William; Aliff, Timothy; Brahmer, Julie; Johnson, David H; Laskin, Janessa L; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pfister, David G; Piantadosi, Steven; Schiller, Joan H; Smith, Reily; Smith, Thomas J; Strawn, John R; Trent, David; Giaccone, Giuseppe

    2009-12-20

    The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

  10. Pilot Testing a Web-Based System for the Assessment and Management of Chemotherapy-Induced Peripheral Neuropathy.

    Science.gov (United States)

    Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M

    2017-04-01

    Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.

  11. Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Konstantinos Bromis

    2017-01-01

    Full Text Available Previous studies in small-cell lung cancer (SCLC patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI. Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN, the Sensorimotor Network, and the Task-Positive Network (TPN. Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.

  12. Chemotherapy-induced peripheral neuropathy: Current status and progress.

    Science.gov (United States)

    Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F

    2016-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options.

  13. Adsorptive voltametry to determine platinum levels in plasma from testicular cancer patients treated with cisplatin

    NARCIS (Netherlands)

    Gelevert, T; Messerschmidt, J; Meinardi, M.T; Alt, F.; Gietema, Harold; Franke, J.P.; Uges, Donald

    2001-01-01

    Patients cured of metastatic testicular cancer with cisplatin chemotherapy may suffer late adverse effects even after 20 years. The cause of these late adverse effects has not been elucidated yet. One cause might be prolonged tissue retention of platinum in these patients. Therefore, an extremely se

  14. Adsorptive voltametry to determine platinum levels in plasma from testicular cancer patients treated with cisplatin

    NARCIS (Netherlands)

    Gelevert, T; Messerschmidt, J; Meinardi, M.T; Alt, F.; Gietema, Harold; Franke, J.P.; Uges, Donald

    2001-01-01

    Patients cured of metastatic testicular cancer with cisplatin chemotherapy may suffer late adverse effects even after 20 years. The cause of these late adverse effects has not been elucidated yet. One cause might be prolonged tissue retention of platinum in these patients. Therefore, an extremely se

  15. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

  16. Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Dong Li

    Full Text Available Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC. Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A, 22q12.2 (rs36600C >T and 5p15.33 (rs401681C >T, significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187 and 0.73 (95% CI, 0.55-0.96; P = 0.0263 compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199 and 1.29 (95% CI, 1.08-1.55; P = 0.0047, respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.

  17. Cardiovascular Events in Cancer Patients Treated with Highly or Moderately Emetogenic Chemotherapy: Results from a Population-Based Study

    Directory of Open Access Journals (Sweden)

    Thao T. Vo

    2012-01-01

    Full Text Available Studies on cardiovascular safety in cancer patients treated with highly or moderately emetogenic chemotherapy (HEC or MEC, who may have taken the antiemetic, aprepitant, have been limited to clinical trials and postmarketing spontaneous reports. Our study explored background rates of cardiovascular disease (CVD events among HEC- or MEC-treated cancer patients in a population-based setting to contextualize events seen in a new drug development program and to determine at a high level whether rates differed by aprepitant usage. Medical and pharmacy claims data from the 2005–2007 IMPACT National Benchmark Database were classified into emetogenic chemotherapy categories and CVD outcomes. Among 5827 HEC/MEC-treated patients, frequencies were highest for hypertension (16–21% and composites of venous (7–12% and arterial thromboembolic events (4–7%. Aprepitant users generally did not experience higher frequencies of events compared to nonusers. Our study serves as a useful benchmark of background CVD event rates in a population-based setting of cancer patients.

  18. Applying quantitative adiposity feature analysis models to predict benefit of bevacizumab-based chemotherapy in ovarian cancer patients

    Science.gov (United States)

    Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; More, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2016-03-01

    How to rationally identify epithelial ovarian cancer (EOC) patients who will benefit from bevacizumab or other antiangiogenic therapies is a critical issue in EOC treatments. The motivation of this study is to quantitatively measure adiposity features from CT images and investigate the feasibility of predicting potential benefit of EOC patients with or without receiving bevacizumab-based chemotherapy treatment using multivariate statistical models built based on quantitative adiposity image features. A dataset involving CT images from 59 advanced EOC patients were included. Among them, 32 patients received maintenance bevacizumab after primary chemotherapy and the remaining 27 patients did not. We developed a computer-aided detection (CAD) scheme to automatically segment subcutaneous fat areas (VFA) and visceral fat areas (SFA) and then extracted 7 adiposity-related quantitative features. Three multivariate data analysis models (linear regression, logistic regression and Cox proportional hazards regression) were performed respectively to investigate the potential association between the model-generated prediction results and the patients' progression-free survival (PFS) and overall survival (OS). The results show that using all 3 statistical models, a statistically significant association was detected between the model-generated results and both of the two clinical outcomes in the group of patients receiving maintenance bevacizumab (pchemotherapy.

  19. Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy.

    Science.gov (United States)

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H W

    2012-09-15

    The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation.

  20. Platinum(II Complexes with Tetradentate Schiff Bases as Ligands: Synthesis, Characterization and Detection of DNA Interaction by Differential Pulse Voltammetry

    Directory of Open Access Journals (Sweden)

    Lijun Li

    2012-01-01

    Full Text Available Five sterically hindered platinum(II complexes with tetradentate schiff bases as ligands, [Pt(L] (L= N,N′-bisalicylidene-1,2-ethylenediamine (L1, N,N′-bisalicylidene-1,2-cyclohexanediamine (L2, N,N′-bis(5-hydroxyl-salicylidene-1,2-cyclohexanediamine (L3, N,N′-bisalicylidene-1,2-diphenyl-ethylenediamine (L4 and N,N′-bis(3-tert-butyl-5-methyl-salicylidene-1,2-diphenylethylenediamine (L5 have been synthesized and characterized by IR spectroscopy and elemental analysis. The sterical hindrance of antitumor drug candidates potentially makes them less susceptible to deactivation by sulphur containing proteins and helping to overcome resistance mechanisms. The interaction of these metal complexes with fish sperm single-stranded DNA (ssDNA was studied electrochemically based on the oxidation signals of guanine and adenine. Differential pulse voltammetry was employed to monitor the DNA interaction in solution by using renewable pencil graphite electrode. The results indicate that ligands with different groups can strongly affect the interaction between [Pt(L] complexes and ssDNA due to sterical hindrances and complex [Pt(L1] has the best interaction with DNA among the five complexes.

  1. Theoretical Study of Nonclassical Platinum Complexes Bonding to Purine Bases: How the Long-lived Monofunctional Adducts Can Be in Existence?

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The B3LYP/6-31G* level of theory was used for the optimization of nonclassical platinum drugs with planar aromatic heterocycle ligands in addition to their monoaqua species, diaqua species and monofunctional adducts. Single point calculations were performed on optimized geometries using the MP2/6-31G** method, and the Lanl2dz pseudo potential for the Pt atom remained constant in all calculations. It can be easily seen that the trans effect can influence both geometrical structures and bond dissociating energies (BDEs). On the basis of our calculation, we get that the long-lived monofunctional adducts with chloride ligand may be in existence, because they possessed higher stability energies, easily dissociated chloride compared with the monoaqua species dissociating chloride and that replacement of the first chloride by bases became exothermic in solution. Our calculated results also demonstrate that the strongest H-bonds appear in the complexes of q-wG and t-wG using different methods. In comparison with adenine complexes, the corresponding guanine complexes possess larger interaction energies as well as higher stability energies either corrected by basis set superposition error (bsse) of Boys-Bernardi counterpoise method or uncorrected both in gas phase and in solution with one exception that the stability energy of q-ClA complex in solution is larger than that of q-ClG complex. Finally, the nature of bond was analyzed in terms of partial charges distribution based on NBO population.

  2. Does cisplatin-based chemotherapy effect on blood lipid levels of patients with germ cell testicular tumor in long-term follow-up?

    Science.gov (United States)

    Koc, Gokhan; Divrik, Taner Rauf; Unlu, Nuri; Bulut, Volkan; Zorlu, Ferruh

    2011-12-01

    Cisplatin-based chemotherapy is widely used in the treatment for germ cell testicular tumors. However, long-term complications of this treatment have gained importance, and hypercholesterolemia is one of these. In some studies, hypercholesterolemia is reported following the cisplatin-based chemotherapy. In this study, we evaluated the relationship of cisplatin-based chemotherapy and blood lipid levels in long-term survivors of patients with germ cell testicular tumors. A total of 89 testicular cancer patients were evaluated between December 1989 and December 2001. Of these, while 39 received cisplatin-based chemotherapy (Group 1), the remaining control group of 50 testicular cancer patients (Group 2) had no adjuvant treatment. The patients in both groups had at least 5-year follow-up and had no known cardiovascular disease. Fasting lipid profiles were obtained including total cholesterol, triglyceride, low- and high-density lipoprotein and very low-density lipoprotein. These values were compared with the normal range, and the statistical difference between the two groups was evaluated. Student's t test was used for continuous variables, and P chemotherapy in germ cell testicular tumors did not have long-term negative effect on blood lipid levels.

  3. Management of chemotherapy-induced nausea and vomiting by risk profile: role of netupitant/palonosetron

    Directory of Open Access Journals (Sweden)

    Lorusso V

    2016-06-01

    Full Text Available Vito Lorusso National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy Abstract: As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV requires the combination of 5-HT3 receptor antagonist (RA with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new antiemetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA is a ready-to-use single oral capsule, combining an NK1-RA (netupitant and a 5-HT3-RA (palonosetron, which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV. Keywords: NEPA, netupitant, NK1, CINV, vomiting, risk factors

  4. Conjugated platinum(IV)-peptide complexes for targeting angiogenic tumor vasculature.

    Science.gov (United States)

    Mukhopadhyay, Sumitra; Barnés, Carmen M; Haskel, Ariel; Short, Sarah M; Barnes, Katie R; Lippard, Stephen J

    2008-01-01

    The integrins alpha vbeta3 and alpha vbeta5 and the membrane-spanning surface protein aminopeptidase N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing RGD, (CRGDC)c, (RGDfK)c, or NGR, is appended as a "tumor-homing device" to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with nonspecific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to cell lines containing alpha vbeta3 and alpha vbeta5, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin alpha vbeta3 mediated, at least in part, the anti-proliferative effect of a Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of alpha vbeta3/alpha vbeta5-specific RGD pentapeptides or (2) transfected with RNAi for beta 3, but not beta 1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment.

  5. Internalization of Ineffective Platinum Complex in Nanocapsules Renders It Cytotoxic.

    Science.gov (United States)

    Vrana, Oldrich; Novohradsky, Vojtech; Medrikova, Zdenka; Burdikova, Jana; Stuchlikova, Olga; Kasparkova, Jana; Brabec, Viktor

    2016-02-18

    Anticancer therapy by platinum complexes, based on nanocarrier-based delivery, may offer a new approach to improve the efficacy and tolerability of the platinum family of anticancer drugs. The original rules for the design of new anticancer platinum drugs were affected by the fact that, although cisplatin (cis-[PtCl2 (NH3)2) was an anticancer drug, its isomer transplatin was not cytotoxic. For the first time, it is demonstrated that simple encapsulation of an inactive platinum compound in phospholipid bilayers transforms it into an efficient cytotoxic agent. Notably, the encapsulation of transplatin makes it possible to overcome the resistance mechanisms operating in cancer cells treated with cisplatin and prevents inactivation of transplatin in the extracellular environment. It is also shown that transplatin delivered to the cells in nanocapsules, in contrast to free (nonencapsulated) complex, forms cytotoxic cross-links on DNA.

  6. Concomitant Radiotherapy and Chemotherapy for High-Risk Nonmelanoma Skin Carcinomas of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Smith Apisarnthanarax

    2011-01-01

    Full Text Available Background. To report on the use and feasibility of a multimodality approach using concomitant radiotherapy and chemotherapy in patients with high-risk nonmelanoma skin carcinoma (NMSC of the head and neck. Methods. Records of patients with NMSC of the head and neck who received concomitant CRT at the University of North Carolina between 2001 and 2007 were reviewed. Results. Fifteen identified patients had at least one of the following high-risk factors: T4 disease (93%, unresectability (60%, regional nodal involvement (40%, and/or recurrence (47%. Ten patients were treated in the definitive setting and five in the postoperative setting. Platinum based chemotherapy was given in 14 (93% patients. Ten of fifteen (67% patients completed all planned chemotherapy treatments, and thirteen patients (87% completed at least 80% of planned chemotherapy. Mild radiation dermatitis occurred in all patients and reached grade 3 in 13% of patients. No patients experienced grade 4 or 5 toxicity. With a median followup of 31 months in surviving patients, the 2-year actuarial locoregional control and relapse-free survival were 79% and 49%, respectively. Conclusions. Definitive or postoperative chemoradiotherapy for patients with locally advanced or regionally metastasized NMSC of the head and neck appears feasible with acceptable toxicities and favorable locoregional control.

  7. Quantitative and qualitative aspects of topoisomerase I and II alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors

    NARCIS (Netherlands)

    van der Zee, A G; de Jong, Steven; Keith, W N; Hollema, H; Boonstra, H; de Vries, Liesbeth

    1994-01-01

    Quantitative and qualitative aspects of topoisomerase (Topo) I and II were studied in 17 malignant ovarian tumors [eight untreated and nine after platinum/cyclophosphamide (Pt/Cy) chemotherapy]. Median Topo II catalytic activity was lower (P <0.05) in tumors after Pt/Cv chemotherapy in comparison to

  8. Inhibition of Notch signaling in combination with paclitaxel reduces platinum-resistant ovarian tumor growth

    Directory of Open Access Journals (Sweden)

    Jolijn W Groeneweg

    2014-07-01

    Full Text Available Introduction: Ovarian cancer (OvCa is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a gamma-secretase inhibitor (GSI in an OvCa patient derived xenograft (PDX model as a single agent therapy and in combination with standard chemotherapy.Methods: Immunocompromised mice bearing xenografts derived from clinically platinum sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003 alone, paclitaxel and carboplatin (P/C alone, or the combination of GSI and P/C. Mice bearing platinum resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups. Results: Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum sensitive ovarian tumors (p < 0.05, as well as in one of three platinum sensitive tumors (p = 0.04. The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum resistant ovarian tumors (all p <0.05. The addition of GSI did not alter the effect of P/C in platinum sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting.Conclusions: Inhibiting the Notch signaling cascade with a GSI reduces primary human xenograft growth in vivo. GSI synergized with conventional cytotoxic chemotherapy only in the platinum resistant OvCa models with single agent paclitaxel. These findings suggest inhibition of the Notch pathway in concert with taxane therapy may hold promise for treatment of platinum resistant OvCa.

  9. E platinum, a newly synthesized platinum compound, induces apoptosis through ROS-triggered ER stress in gastric carcinoma cells.

    Science.gov (United States)

    Wang, Xiaoping; Guo, Qinglong; Tao, Lei; Zhao, Li; Chen, Yan; An, Teng; Chen, Zhen; Fu, Rong

    2017-01-01

    Gastric cancer (GC) is still one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the antitumor effect of E Platinum, a newly platinum-based chemotherapeutic agent bearing the basic structure of Oxaliplatin, in a variety of gastric carcinoma cells and the underlying mechanisms. We demonstrated that E Platinum significantly induced apoptosis in gastric cancer cells via mitochondrial apoptotic pathway as a result of increased reactive oxygen species (ROS). We also found that E Platinum enhanced Ca(2+) flux out from the endoplasmic reticulum by increasing the protein expression of IP3R type 1 (IP3R1) and decreasing the expression of ERp44. Dysfunction of Ca(2+) homeostasis in endoplasmic reticulum (ER) leads to accumulation of unfolded proteins and ER stress. Mechanically, E Platinum increased ER stress associated protein expression such as GRP78, p-PERK, p-eIF2α, ATF4, and CHOP. However, knocking down CHOP reversed E Platinum-induced apoptosis by blocking mitochondrial apoptotic pathway. Furthermore, 10 mg/kg of E Platinum significantly suppressed BGC-823 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, E Platinum inhibited tumor growth and induced apoptosis by ROS-mediated ER stress activation both in vitro and in vivo. Our study indicated that E Platinum may be a potential and effective treatment for gastric cancer in clinical. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2- Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study.

    Science.gov (United States)

    Li, Nanxin; Hao, Yanni; Xie, Jipan; Lin, Peggy L; Koo, Valerie; Ohashi, Erika; Wu, Eric Q

    2015-01-01

    Objective. To compare the real-world effectiveness of everolimus-based therapy and chemotherapy in postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Methods. This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2- mBC women in community-based oncology practices. Patients received everolimus-based therapy or chemotherapy for mBC between 07/01/2012 and 04/15/2013, after failure of a non-steroidal aromatase inhibitor. Overall survival (OS), progression-free survival (PFS), and time on treatment (TOT) were compared using Kaplan-Meier analysis and Cox proportional hazards models adjusting for line of therapy and baseline characteristics. Results. 234 and 137 patients received everolimus-based therapy and chemotherapy. Patients treated with everolimus-based therapy tended to have less aggressive mBC than patients treated with chemotherapy. Multivariate-adjusted Cox models showed that everolimus-based therapy was associated with significantly longer OS [hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.22-0.63], PFS (HR = 0.70, 95% CI = 0.50-0.97), and TOT (HR = 0.34, 95% CI: 0.25-0.45) than chemotherapy. Adjusted comparative effectiveness results were generally consistent across lines of therapy. Conclusion. In this retrospective chart review of postmenopausal HR+/HER2- mBC patients, treatment with everolimus-based therapy was associated with longer OS, PFS, and TOT than chemotherapy.

  11. Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer. A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Li-Yang; Xie, Hua; Zhou, Hang; Yao, Wen-Xiu; Zhao, Xin; Wang, Yi

    2017-01-01

    To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC). PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies. A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p less than 0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95%CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting. The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients.

  12. Platinum nitride with fluorite structure

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Rong; Zhang, Xiao-Feng

    2005-01-31

    The mechanical stability of platinum nitride has been studied using first-principles calculations. By calculating the single-crystal elastic constants, we show that platinum nitride can be stabilized in the fluorite structure, in which the nitrogen atoms occupy all the tetrahedral interstitial sites of the metal lattice. The stability is attributed to the pseudogap effect from analysis of the electronic structure.

  13. Clinical Implications of HER-2 and P53 in Taxane-Based and Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaolan Wang; Fan Yao; Nan Liu; Yunfei Wu; Xinyu Zheng; Jiguang Li; Caigang Liu; Xueshan Qiu; Feng Jin

    2008-01-01

    OBTECTIVE To evaluate the predictive value of human epidermal growth factor receptor-2(HER-2)and P53 in taxane-based and anthracycline-based neoadjuvant chemotherapy(NAC)in breast cancer. METHODS Sixty-two patients with breast cancer were included in this study. Twenty-two patients were treated with taxane-based(taxane group) and 40 with anthracycline-based(anthracycline group).ER,PR,c-erbB2 and P53 were detected by immunohistochemistry staining before NAC, and Fluorescence In Situ Hybridization(FISH)was used to detect the HER-2 gene amplification for the cases with the expression of c-erbB2 protein as(++)or(+++).The efficacy of the regimens was evaluated after NAC. RESULTS In the anthracycline group, objective response(OR)was observed in 30 out of 40 patients(75%),whereas no response(NR)was observed in 10 patients(25%).In the taxane group, OR was observed in 15 patients out of 22 patients(68.2%), whereas NR was observed in 7 patients(31.8%).HER-2-negative status was correlated with a high OR in both taxane-based and anthracycline-based NAC(P=0.023 and P=0.029),whereas P53-negative status was correlated with high OR rate in anthracycline-based NAC(P=0.041).The significant difference of the CR rates was observed between the patients took<4 cycles and≥4 cycles NAC (4.65%vs.21.05%,P<0.05).CONCLUSION The patients with HER-2 gene non-amplication may be sensitive to both taxane-based and anthracycline-based chemotherapy; the patients without P53 overexpression may suitable to select anthracycline-based chemotherapy; and proper increased NAC cycles may increase CR rates.

  14. The molecular shape and the field similarities as criteria to interpret SAR studies for fragment-based design of platinum(IV) anticancer agents. Correlation of physicochemical properties with cytotoxicity.

    Science.gov (United States)

    Lorenzo, Julia; Montaña, Ángel M

    2016-09-01

    Molecular shape similarity and field similarity have been used to interpret, in a qualitative way, the structure-activity relationships in a selected series of platinum(IV) complexes with anticancer activity. MM and QM calculations have been used to estimate the electron density, electrostatic potential maps, partial charges, dipolar moments and other parameters to correlate the stereo-electronic properties with the differential biological activity of complexes. Extended Electron Distribution (XED) field similarity has been also evaluated for the free 1,4-diamino carrier ligands, in a fragment-based drug design approach, comparing Connolly solvent excluded surface, hydrophobicity field surface, Van der Waals field surface, nucleophilicity field surface, electrophilicity field surface and the extended electron-distribution maxima field points. A consistency has been found when comparing the stereo-electronic properties of the studied series of platinum(IV) complexes and/or the free ligands evaluated and their in vitro anticancer activity.

  15. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment

    Science.gov (United States)

    Martinez-Trufero, J; Isla, D; Adansa, J C; Irigoyen, A; Hitt, R; Gil-Arnaiz, I; Lambea, J; Lecumberri, M J; Cruz, J J

    2010-01-01

    Background: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. Methods: Patients aged 18–75 years, with Eastern Cooperative Oncology Group performance status 0–2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m−2 BID) was administered on days 1–14 every 21 days for at least two cycles. Results: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1–9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). Conclusions: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules. PMID:20485287

  16. Porous platinum nanotubes labeled with hemin/G-quadruplex based electrochemical aptasensor for sensitive thrombin analysis via the cascade signal amplification.

    Science.gov (United States)

    Sun, Aili; Qi, Qingan; Wang, Xuannian; Bie, Ping

    2014-07-15

    For the first time, a sensitive electrochemical aptasensor for thrombin (TB) was developed by using porous platinum nanotubes (PtNTs) labeled with hemin/G-quadruplex and glucose dehydrogenase (GDH) as labels. Porous PtNTs with large surface area exhibited the peroxidase-like activity. Coupling with GDH and hemin/G-quadruplex as NADH oxidase and HRP-mimicking DNAzyme, the cascade signal amplification was achieved by the following ways: in the presence of glucose and NAD(+) in the working buffer, GDH electrocatalyzed the oxidation of glucose with the production of NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed the oxidation of NADH to in situ generate H2O2. Based on the corporate electrocatalysis of PtNTs and hemin/G-quadruplex toward H2O2, the electrochemical signal was significantly amplified, allowing the detection limit of TB down to 0.15 pM level. Moreover, the proposed strategy was simple because the intercalated hemin offered the readout signal, avoiding the adding of additional redox mediator as signal donator. Such an electrochemical aptasensor is highly promising for sensitive detection of other proteins in clinical diagnostics.

  17. Amperometric Biosensor Based on Diamine Oxidase/Platinum Nanoparticles/Graphene/Chitosan Modified Screen-Printed Carbon Electrode for Histamine Detection.

    Science.gov (United States)

    Apetrei, Irina Mirela; Apetrei, Constantin

    2016-03-24

    This work describes the development and optimization studies of a novel biosensor employed in the detection and quantification of histamine in freshwater fish samples. The proposed biosensor is based on a modified carbon screen-printed electrode with diamineoxidase, graphene and platinum nanoparticles, which detects the hydrogen peroxide formed by the chemical process biocatalysed by the enzyme diamine oxidase and immobilized onto the nanostructurated surface of the receptor element. The amperometric measurements with the biosensor have been implemented in buffer solution of pH 7.4, applying an optimal low potential of +0.4 V. The novel biosensor shows high sensitivity (0.0631 μA·μM), low detection limit (2.54 × 10(-8) M) and a broad linear domain from 0.1 to 300 μM. The applicability in natural complex samples and the analytical parameters of this enzyme sensor have been performed in the quantification of histamine in freshwater fish. An excellent correlation among results achieved with the developed biosensor and results found with the standard method for all freshwater fish samples has been achieved.

  18. Study on separation of platinum group metals from high level liquid waste using macroporous (MOTDGA-TOA)/SiO{sub 2}-P silica-based absorbent

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tatsuya [Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University, Aoba 6-6, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579 (Japan); Japan Atomic Energy Agency, Tokai-mura Naka-gun, Ibarak319-1195 (Japan); Kim, Seong-Yun; Xu, Yuanlai; Hitomi, Keitaro [Cyclotron and Radioisotope Center, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578 (Japan); Ishii, Keizo [Department of Quantum Science and Energy Engineering, Graduate School of Engineering, Tohoku University, Aoba 6-6, Aramaki, Aoba-ku, Sendai, Miyagi 980-8579 (Japan); Nagaishi, Ryuji; Kimura, Takaumi [Japan Atomic Energy Agency, Tokai-mura Naka-gun, Ibarak319-1195 (Japan)

    2013-07-01

    The recovery of platinum group metals (PGMs) from high level liquid waste (HLLW) by macroporous silica-based adsorbent, (MOTDGA-TOA)/SiO{sub 2}-P has been developed by impregnating two extractants of N,N'-dimethyl-N,N'-di-n-octyl-thio-diglycolamide (MOTDGA) and tri-n-octylamine (TOA) into a silica/polymer composite support (SiO{sub 2}-P). The adsorption of Ru(III), Rh(III) and Pd(II) have been investigated in simulated HLLW by batch method. The adsorbent has shown good uptake property for Pd(II). In addition, the combined use of MOTDGA and TOA improved the adsorption of Ru(III) and Rh(III) better than the individual use of them. The usability of adsorbent in radiation fields was further confirmed by irradiation experiments. The adsorbent remained to have the uptake capability for PGMs over the absorbed dose of 100 kGy, corresponding with one really adsorbed by the adsorbent, and showed good retention capability for Pd(II) even at the absorbed dose of 800 kGy. The chromatographic separation of metal ions was demonstrated with the adsorbent packed column, there is no influence of Re(VII) (instead of Tc) on the excellent separation behavior of Pd(II). (authors)

  19. Expression of p21WAF1 in Astler-Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy.

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Urasinska, Elzbieta; Bielicki, Dariusz; Safranow, Krzysztof; Domagala, Wenancjusz

    2011-04-01

    In several, but not all, previous studies, positive p21(WAF1) expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21(WAF1) expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler-Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21(WAF1) was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21(WAF1) was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21(WAF1) expression but not in the subgroup of 61 stage B2 patients with negative p21(WAF1) expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21(WAF1) expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21(WAF1) in colorectal tumor cells identifies a subgroup of Astler-Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy.

  20. A Prognostic Model Using Inflammation- and Nutrition-Based Scores in Patients With Metastatic Gastric Adenocarcinoma Treated With Chemotherapy.

    Science.gov (United States)

    Hsieh, Meng-Che; Wang, Shih-Hor; Chuah, Seng-Kee; Lin, Yu-Hung; Lan, Jui; Rau, Kun-Ming

    2016-04-01

    The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy.After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances.Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P nutrition-based scores could provide prognostic information to patients and physicians.

  1. Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy

    Science.gov (United States)

    Rotoli, Deborah; Morales, Manuel; Del Carmen Maeso, María; Del Pino García, María; Morales, Araceli; Ávila, Julio; Martín-Vasallo, Pablo

    2016-01-01

    The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker. PMID:27446431

  2. Changes in taste and smell function, dietary intake, food preference, and body composition in testicular cancer patients treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    IJpma, Irene; Renken, Remco J; Gietema, Jourik A; Slart, Riemer H J A; Mensink, Manon G J; Lefrandt, Joop D; Ter Horst, Gert J; Reyners, Anna K L

    2016-10-27

    Taste and smell changes due to chemotherapy may contribute to the high prevalence of overweight in testicular cancer patients (TCPs). This study investigates the taste and smell function, dietary intake, food preference, and body composition in TCPs before, during, and up to 1 year after cisplatin-based chemotherapy. Twenty-one consecutive TCPs participated. At baseline TCPs were compared to healthy controls (N = 48). Taste strips and 'Sniffin' Sticks' were used to determine psychophysical taste and smell function. Subjective taste, smell, appetite, and hunger were assessed using a questionnaire. Dietary intake was analyzed using a food frequency questionnaire. Food preference was assessed using food pictures varying in taste (sweet/savoury) and fat or protein content. A Dual-Energy X-ray Absorptiometry (DEXA) scan was performed to measure whole body composition. Compared to controls, TCPs had a lower smell threshold (P = 0.045) and lower preference for high fat sweet foods at baseline (P = 0.024). Over time, intra-individual psychophysical taste and smell function was highly variable. The salty taste threshold increased at completion of chemotherapy compared to baseline (P = 0.006). A transient decrease of subjective taste, appetite, and hunger feelings was observed per chemotherapy cycle. The percentage of fat mass increased during chemotherapy compared to baseline, while the lean mass and bone density decreased (P < 0.05). Coping strategies regarding subjective taste impairment should especially be provided during the first week of each chemotherapy cycle. Since the body composition of TCPs already had changed at completion of chemotherapy, intervention strategies to limit the impact of cardiovascular risk factors should probably start during treatment. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUO Ming-lei; DUAN Jian-chun; WANG Yu-yan; GUO Qing-zhi; LIU Xu-yi; LIU Ning-hong; WANG Jie; WU Mei-na; ZHAO Jun; Sonya Wei Song; BAI Hua; WANG Shu-hang; YANG Lu; AN Tong-tong; WANG Xin

    2011-01-01

    Background The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy,but its role in cytotoxic chemotherapy is still unknown.Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy.Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).In this study,we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department.We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.Results There were 54 patients with known EGFR mutations and 91 cases of wild types.No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs.31.9%).The median survival time and 1-,2-year survival rates were higher in mutation carriers than wild-types (24months vs.18 months,85.7% vs.65.7% and 43.7% vs.25.9%,P=0.047).Clinical stage (IV vs.Ⅲb),response to the first-line chemotherapy (partial vs.no) and EGFR genotype were independent prognostic factors.Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy,but an independent prognostic factor indicating longer survival.

  4. 基于 ADS1247的小型计量检定铂电阻温度计设计%The Miniature Platinum resistor temperature gauge for Metrology Calibration based on ADS1247r

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    To solve the problem of low precision and complex structure of platinum resistor temperature gauge for metrology calibration in the range of -30-300℃ ,this paper presents a design scheme of miniature platium resistor temperature gauge for metrology calibration based on ADS1247 of TI corp.The programmable constant-current source of ADS1247 is used as exciting source of platinum resistor.The programmable amplifier of ADS1247 is adopted to amplified the voltage drop of platinum resistor during the course of measurement,and the output voltage of amplifier was digitalized by a 24-bit analog-to-digital converter. According to the experiment,the measurement precision of platinum resistor temperature gauge can reach to 0.05℃ ,and the resolution can reach to 0.004℃.%  针对当前在-30-300℃范围内铂电阻计量检定温度计存在结构复杂、精度较低的问题,本文提出一种基于 TI 公司ADS1247的小型计量检定用铂电阻温度计的设计方案。将 ADS1247输出的可编程恒定电流作为铂电阻激励源。测量过程中,采用 ADS1247集成的可编程放大器放大铂电阻的电压降,并将放大器输出信号进行24位的 AD 转换。通过实验测试,基于ADS1247的铂电阻温度计精度可达到0.05℃,分辨率可达到0.004℃。

  5. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Lesiuk, Teresa

    2016-08-09

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

  6. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

    Science.gov (United States)

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

  7. Arsenic-Based Drugs: From Fowler's Solution to Modern Anticancer Chemotherapy

    Science.gov (United States)

    Gibaud, Stéphane; Jaouen, Gérard

    Although arsenic is a poison and has a predominantly unfavorable reputation, it has been used as pharmaceutical agent since the first century BC. In 1786, Thomas Fowler reported the effects of arsenic in the cure of agues, remittent fevers, and periodic headaches. From this time on and despite abusive use, some interesting indications began to appear for trypanosomiasis, syphilis, and blood diseases. The first significant organoarsenical drug (atoxyl) was synthesized by Pierre Antoine Béchamp in 1859 by chemically reacting arsenic acid with aniline but additional experimentations on the properties of arsenic led Paul Ehrlich, the founder of chemotherapy, to the discovery of salvarsan in 1910. From the Second World War, Ernst A.H. Friedheim greatly improved the treatment of trypanosomiasis by melaminophenyl arsenicals. Until the 1990s some organoarsenicals were used for intestinal parasite infections but carcinogenic effects were displayed and all the drugs have been withdrawn in USA, in Europe, and elsewhere. In 2003, arsenic trioxide (Trisenox®) was re-introduced for the treatment of very specific hematological malignancies.

  8. Biocompatible CuS-based nanoplatforms for efficient photothermal therapy and chemotherapy in vivo.

    Science.gov (United States)

    Peng, Shuwen; He, Yuanyuan; Er, Murat; Sheng, Yuanzhi; Gu, Yueqing; Chen, Haiyan

    2017-02-28

    Near-infrared (NIR) photothermal therapy (PTT) is a new approach to ablate cancer without affecting normal tissues. A pivotal concern of PPT is to develop photo-responsive agents with high biocompatibility as well as effective photothermal conversion efficiency. Copper sulfide (CuS) nanoparticles prepared are characterized by their low synthesis cost, wide NIR absorption range, good biocompatibility and favorable NIR photothermal conversion efficiency. CuS nanoparticles were then coated with mesoporous silicon dioxide (SiO2) by the Stober method, and further loaded with anticancer drug doxorubicin (DOX). The nanocomposites obtained were named CuS@MSN-DOX. The infrared thermal imaging of CuS@MSN-DOX demonstrated its favorable photothermal efficacy. The potential of CuS@MSN-DOX utilized as a multifunctional platform for combined PPT and chemotherapy was exploited both at the cell level and in a mice model. The result demonstrated that CuS@MSN-DOX was endowed with the synergistic effect of chemo-photothermal therapy, which confirmed that it is a promising candidate for combined therapy of cancer.

  9. MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Jensen, S; Vainer, B

    2009-01-01

    >T and 1298A>C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01). Conclusions: The MTHFR 677C>T and 1298A>C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal......Methylenetetrahydrofolate reductase is a pivotal enzyme in folate metabolism and 5-fluorouracil (5-FU) cytotoxicity. Two common single-nucleotide polymorphisms (SNPs), MTHFR 677C>T (rs1801133) and 1298A>C (rs1801131), reduce enzyme activity. Initially, these SNPs were claimed to predict clinical....../leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C>T and 1298A>C SNPs with real-time PCR. Results: The MTHFR 677C...

  10. Effect of an Educational-Supportive Program Based on Roy Adaptation Model on Marital Satisfaction in Mastectomy Patients Receiving Chemotherapy

    Directory of Open Access Journals (Sweden)

    Samira Shahed

    2016-04-01

    Full Text Available Background: Regarding nurses' significant role in improving quality of marital life in mastectomy patients and their families, implication of the adaptation model can help nurses reaching this goal. Aim: This study aimed to determine Effect of an educational-supportive program based on Roy This quasi-experimental study was performed on 69 mastectomy patients receiving chemotherapy in 2013 in clinical services in Tehran, Iran. The samples were randomly allocated to two groups. The data collection instrument was ENRICH Marital Satisfaction scale (2011. In the experimental group, maladaptive behaviors and their stimuli were determined by the questionnaire, and then adaptive strategies were implemented in 45 days. The program was based on support (patients instruction, peer group, weblog, meeting with the participants’ spouses, and three-month follow-up using behaviors checklist. Control group patients received the regular treatment sessions. T-test, Pearson’s correlation coefficient, Spearman's rank correlation coefficient, and Chi-square tests were run, using SPSS version 19. Results: In experimental group, paired sample t-test reflected an increase in marital satisfaction from 24.7±2.6 before to 32.9±3.5 after the intervention (P=0.03. However, no significant differences were observed in the control group from 26/7±4/6 before to 26/5±4/8 after the intervention in this regard (P=0/63.   Implications for Practice: Roy Adaptation Model can be used as a framework for designing educational-supportive programs to improve quality of marital life in mastectomy patients receiving chemotherapy.

  11. Lowering the resistivity of polyacrylate ion-selective membranes by platinum nanoparticles addition.

    Science.gov (United States)

    Jaworska, Ewa; Kisiel, Anna; Maksymiuk, Krzysztof; Michalska, Agata

    2011-01-01

    The effect of platinum nanoparticles introduction into polyacrylate membranes was examined. Platinum nanoparticles were added to the membrane cocktail before photopolymerization of the poly(n-butyl acrylate) based ion-selective membranes. Thus obtained sensors were characterized with significantly lowered electrical resistance and increased stability of potential readings compared to classical poly(n-butyl acrylate) membranes. The analytical parameters of platinum nanoparticle containing membranes were well comparable with those of classical membranes.

  12. Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

    Institute of Scientific and Technical Information of China (English)

    Sheng-xiang Ren; Cai-cun Zhou; Ai-wu Li; Song-wen Zhou; Ling Zhang; Yong-sheng Wang; Bing Li; Xiao-xia Chen; Jie Zhang; Jian-fang Xu

    2012-01-01

    Objective:Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 (BRCA1) gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 (RRM1) gene overexpression enhances resistance to gemcitabine.To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer (NSCLC),we performed this non-randomized phase Ⅱclinical trial which tested the hypothesis that customized therapy would confer improved outcome over noncustomized therapy.Methods:RNA was isolated from fresh tumor tissue.Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels:both Iow-cisplatin plus gemcitabine (GP); both high-vinorelbine plus cisplatin (NP);BRCA1 low and RRM1 high-cisplatin plus docetaxel (TP); BRCA1 high and RRM1 Iow-vinorelbine plus gemcitabine (GN).Results:From Dec 2005 to Nov 2008,94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study.The median age was 58 years old.Among them,21 patients received GP,30 patients received TP and 43 patients received NP chemotherapy.GP group had a higher response rate,and longer median time to progression (TTP) and median overall survival (OS) time than the other 2 groups.The response rates in the GP,TP and NP groups were 42.9%,36.7% and 27.9%,respectively (P=0.568).The median TTP was 5.6,5.0,4.8 months (P=0.975),respectively,and the median OS time was 12.5,11.0,9.7 months (P=0.808),respectively.Conclusion:Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group.This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

  13. Longitudinal risk of herpes zoster in patients with non-Hodgkin lymphoma receiving chemotherapy: A nationwide population-based study.

    Science.gov (United States)

    Cho, Shih-Feng; Wu, Wan-Hsuan; Yang, Yi-Hsin; Liu, Yi-Chang; Hsiao, Hui-Hua; Chang, Chao-Sung

    2015-09-22

    This study investigated the incidence of and risk factors for herpes zoster in patients with non-Hodgkin lymphoma (NHL) who were receiving anti-lymphoma treatment. The overall incidence density of herpes zoster was 12.21% (472/3865); 11.79% (258/2188) of the patients received conventional chemotherapy and 12.76% (214/1677) of the patients received rituximab-containing chemotherapy. For the patients who received conventional chemotherapy, the risk factors included female gender, multiple courses of chemotherapy and autologous hematopoietic stem cell transplantation. For the patients who received rituximab-containing chemotherapy, the risk factors included female gender, diabetes mellitus, multiple courses of chemotherapy, autologous hematopoietic stem cell transplantation and higher accumulated rituximab dose. The majority of the herpes zoster episodes occurred within the first two years after the diagnosis of NHL. After adjusting for the propensity score matching, rituximab-containing chemotherapy was not associated with a higher overall incidence density of herpes zoster (P = 0.155). However, the addition of rituximab to conventional chemotherapy increased the short-term risk of herpes zoster with adjusted odd ratios of 1.38 (95% confidence intervals (CI) = 1.05-1.81, P = 0.021) and 1.37 (95% CI = 1.08-1.73, P = 0.010) during the 1-year and 2-year follow-up periods, respectively.

  14. Platinum recycling going green via induced surface potential alteration enabling fast and efficient dissolution

    Science.gov (United States)

    Hodnik, Nejc; Baldizzone, Claudio; Polymeros, George; Geiger, Simon; Grote, Jan-Philipp; Cherevko, Serhiy; Mingers, Andrea; Zeradjanin, Aleksandar; Mayrhofer, Karl J. J.

    2016-01-01

    The recycling of precious metals, for example, platinum, is an essential aspect of sustainability for the modern industry and energy sectors. However, due to its resistance to corrosion, platinum-leaching techniques rely on high reagent consumption and hazardous processes, for example, boiling aqua regia; a mixture of concentrated nitric and hydrochloric acid. Here we demonstrate that complete dissolution of metallic platinum can be achieved by induced surface potential alteration, an ‘electrode-less' process utilizing alternatively oxidative and reductive gases. This concept for platinum recycling exploits the so-called transient dissolution mechanism, triggered by a repetitive change in platinum surface oxidation state, without using any external electric current or electrodes. The effective performance in non-toxic low-concentrated acid and at room temperature is a strong benefit of this approach, potentially rendering recycling of industrial catalysts, including but not limited to platinum-based systems, more sustainable. PMID:27767178

  15. Platinum recycling going green via induced surface potential alteration enabling fast and efficient dissolution

    Science.gov (United States)

    Hodnik, Nejc; Baldizzone, Claudio; Polymeros, George; Geiger, Simon; Grote, Jan-Philipp; Cherevko, Serhiy; Mingers, Andrea; Zeradjanin, Aleksandar; Mayrhofer, Karl J. J.

    2016-10-01

    The recycling of precious metals, for example, platinum, is an essential aspect of sustainability for the modern industry and energy sectors. However, due to its resistance to corrosion, platinum-leaching techniques rely on high reagent consumption and hazardous processes, for example, boiling aqua regia; a mixture of concentrated nitric and hydrochloric acid. Here we demonstrate that complete dissolution of metallic platinum can be achieved by induced surface potential alteration, an `electrode-less' process utilizing alternatively oxidative and reductive gases. This concept for platinum recycling exploits the so-called transient dissolution mechanism, triggered by a repetitive change in platinum surface oxidation state, without using any external electric current or electrodes. The effective performance in non-toxic low-concentrated acid and at room temperature is a strong benefit of this approach, potentially rendering recycling of industrial catalysts, including but not limited to platinum-based systems, more sustainable.

  16. Tuning the activity of platinum(IV) anticancer complexes through asymmetric acylation.

    Science.gov (United States)

    Chin, Chee Fei; Tian, Quan; Setyawati, Magdiel Inggrid; Fang, Wanru; Tan, Emelyn Sue Qing; Leong, David Tai; Ang, Wee Han

    2012-09-13

    Platinum(II) anticancer drug cisplatin is one of the most important chemotherapeutic agents in clinical use but is limited by its high toxicity and severe side effects. Platinum(IV) anticancer prodrugs can overcome these limitations by resisting premature aquation and binding to essential plasma proteins. Structure-activity relationship studies revealed a link between the efficacy of platinum(IV) complexes with the nature of their axial ligands, which can be modified to enhance the properties of the prodrug. The existing paradigm of employing platinum(IV) complexes with symmetrical axial carboxylate ligands does not fully exploit their vast potential. A new approach was conceived to control properties of platinum(IV) prodrugs using contrasting axial ligands via sequential acylation. We report a novel class of asymmetric platinum(IV) carboxylates based on the cisplatin template containing both hydrophilic and lipophilic ligands on the same scaffold designed to improve their aqueous properties and enhance their efficacy against cancer cells in vitro.

  17. Solid-state materials for anion sensing in aqueous solution: highly selective colorimetric and luminescence-based detection of perchlorate using a platinum(II) salt.

    Science.gov (United States)

    Taylor, Stephen D; Howard, Whitney; Kaval, Necati; Hart, Robert; Krause, Jeanette A; Connick, William B

    2010-02-21

    The PF(6)(-) salt of a platinum(II) complex changes from yellow to red and becomes intensely luminescent upon exposure to aqueous ClO(4)(-). The response is remarkably selective. Spectroscopic changes are consistent with anion exchange resulting in shortening of the intramolecular PtPt distances between the square planar cations.

  18. Solid-state materials for anion sensing in aqueous solution: highly selective colorimetric and luminescence-based detection of perchlorate using a platinum(II) salt

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Stephen D.; Howard, Whitney; Kaval, Necati; Hart, Robert; Krause, Jeanette A.; Connick, William B. (UCIN); (Shepherd)

    2010-07-23

    The PF{sub 6}{sup -} salt of a platinum(II) complex changes from yellow to red and becomes intensely luminescent upon exposure to aqueous ClO{sub 4}{sup -}. The response is remarkably selective. Spectroscopic changes are consistent with anion exchange resulting in shortening of the intramolecular Pt***Pt distances between the square planar cations.

  19. BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy.

    Directory of Open Access Journals (Sweden)

    Yong Gao

    Full Text Available BACKGROUND: The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1 expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qPCR was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments. RESULTS: Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively and median overall survival (mOS; P = 0.002 and P<0.001, respectively in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively and mOS (both P<0.001 in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007 or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001 group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001 or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001 group. CONCLUSIONS: BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.

  20. Synthesis of Bimetallic Platinum Nanoparticles for Biosensors

    Directory of Open Access Journals (Sweden)

    Gerard M. Leteba

    2013-08-01

    Full Text Available The use of magnetic nanomaterials in biosensing applications is growing as a consequence of their remarkable properties; but controlling the composition and shape of metallic nanoalloys is problematic when more than one precursor is required for wet chemistry synthesis. We have developed a successful simultaneous reduction method for preparation of near-spherical platinum-based nanoalloys containing magnetic solutes. We avoided particular difficulties in preparing platinum nanoalloys containing Ni, Co and Fe by the identification of appropriate synthesis temperatures and chemistry. We used transmission electron microscopy (TEM to show that our particles have a narrow size distribution, uniform size and morphology, and good crystallinity in the as-synthesized condition. Energy dispersive spectroscopy (EDS and X-ray diffraction (XRD confirms the coexistence of Pt with the magnetic solute in a face-centered cubic (FCC solid solution.

  1. Chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Javier Sastre; Jose Angel García-Saenz; Eduardo Díaz-Rubio

    2006-01-01

    Metastatic gastric cancer remains a non-curative disease.Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed.Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116study, postoperative chemoradiation has been Accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease.Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱstudies are showing promising results. Phase Ⅲ trials are needed.

  2. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer.

    Science.gov (United States)

    Wang, Yuxia; Xu, Ye; Chen, Jiuan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2016-01-15

    The role of TP53 mutations in predicting response to neoadjuvant chemotherapy in breast cancer remains controversial. The aims of this study were to investigate whether TP53 mutations were associated with response and survival in breast cancer patients who received neoadjuvant chemotherapy. Therefore, we identified TP53 mutations in the core-needle biopsy tumor samples obtained before the neoadjuvant chemotherapy from 351 operable primary breast cancer patients who either received anthracycline/cyclophosphamide-based (n = 252) or paclitaxel (n = 99) neoadjuvant chemotherapy. We found that 41.0% (144 of 351) of patients harbored TP53 mutations, and 14.8% of patients achieved a pCR (pathologic complete response) after neoadjuvant chemotherapy. Among patients treated with anthracycline/cyclophosphamide (n = 252), patients with TP53 mutations had a significantly higher pCR rate than those with wild-type (28.6 vs.7.1%; p TP53 mutation was an independent favorable predictor of pCR [odds ratio (OR) = 3.41; 95% confidence interval (CI) 1.50-7.77; p = 0.003] in this group; moreover, patients with TP53 mutation had a better distant recurrence-free survival (DRFS) than those with wild-type [unadjusted hazard ratio (HR) = 0.43; 95% CI 0.20-0.94; p = 0.030] in this group. Among patients treated with paclitaxel (n = 99), no significant difference in pCR rates was observed between patients with or without TP53 mutations (15.2 vs. 11.3%; p = 0.57). Our results suggested that patients with TP53 mutations are more likely to respond to anthracycline/ cyclophosphamide-based neoadjuvant chemotherapy and have a favorable survival.

  3. Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郏博

    2014-01-01

    Objective To explore the association between different epidermal growth factor receptor(EGFR)mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer(NSCLC).Methods A retrospective cohort study was performed to assess146 patients with advanced NSCLC at Cancer

  4. Types of chemotherapy

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  5. Chemotherapy for Thyroid Cancer

    Science.gov (United States)

    ... Type and Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  6. Chemotherapy for Testicular Cancer

    Science.gov (United States)

    ... Type and Stage Testicular Cancer Treating Testicular Cancer Chemotherapy for Testicular Cancer Chemotherapy (chemo) is the use of drugs to treat ... that is only in the testicle. Doctors give chemotherapy in cycles, with each period of treatment followed ...

  7. Side Effects of Chemotherapy

    Science.gov (United States)

    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  8. Chemotherapy and Your Mouth

    Science.gov (United States)

    ... Treatment and Oral Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being ... Problems Too? Remember Are You Being Treated With Chemotherapy for Cancer? If so, this booklet can help ...

  9. Potentiometric determination of trace amounts of aluminium utilizing polyvinyl chloride membrane and coated platinum sensors based on E-N'-(2-hydroxy-3-methoxybenzylidene) benzohydrazide.

    Science.gov (United States)

    Tajik, Somayeh; Taher, Mohammad Ali; Sheikhshoaie, Iran

    2013-01-01

    This paper describes the construction and performance characteristics of novel polyvinyl chloride membrane (PME) and coated platinum (CPtE) aluminium (Al) ion selective electrodes based on E-N'-(2-hydroxy-3-methoxybenzylidene) benzohydrazide. The electrodes exhibited linear responses with near Nernstian slopes of 19.9 +/- 0.3 (PME) and 20.1 +/- 0.4 (CPtE) mV/decade of activity within the Al3+ ion concentration range of 3.0 x 10(-7) to 1.0 x 10(-2) M for the PME and 1.0 x 10(-7)-1.0 x 10(-2) M for the CPtE. These sensors were applicable in a pH range of 3.0 to 7.0. The LODs of the PME and CPtE were 1.7 x 10(-7) and 5.6 x 10(-8) M, respectively. They had a response time of less than 10 s and could be used practically for a period of at least 2 months without measurable divergence in results. The isothermal temperature coefficient of the PME was 1.12 x 10(-3) V/degrees C, and it can tolerate partially nonaqueous media up to 25%. The electrodes showed excellent selectivity towards Al3+ ions in the presence of a wide range of alkali, alkaline earth, and transition metals ions. They were successfully applied for the direct determination of Al3+ ions in tap water, aqueduct water, mineral water, and Al-Mg syrup and as indicator electrodes in potentiometric titration of Al ions with EDTA.

  10. Structural, elastic, electronic and optical properties of platinum-based superconductor SrPt3P under pressure: a first-principles study

    Science.gov (United States)

    Zhang, Xiu-Qing; Li, Guo-Jun; Cheng, Yan; Ji, Guang-Fu

    2016-02-01

    The structural, elastic, electronic and optical properties of the platinum-based superconductor SrPt3P under pressure are investigated by the generalized gradient approximation with the Perdew-Burke-Ernzerhof exchange-correlation functional in the framework of density-functional theory. The calculated structural parameters (a, c) and the primitive cell volume V of SrPt3P at the ground state are in good agreement with the available experimental data and seem to be better than other calculated results. The pressure dependences of the elastic constants Cnolimitsij, bulk modulus B, shear modulus G, Young's modulus E and Poisson's ratio σ of SrPt3P are also obtained successfully. The computed elastic constants indicate that SrPt3P is mechanically stable up to 100 GPa. The obtained B/G is 2.56 at the ground state, indicating that SrPt3P behaves in a ductile manner. The ratio B/G also increases with growing pressures, indicating that the structure becomes more and more ductile. Even though SrPt3P is an ionic-covalent crystal, the obtained density of states shows that it has metallic characteristic. These conclusions can be further demonstrated by analysing the charge and Mulliken population. In addition, we have investigated the dielectric function and the loss function. It is found that the dielectric function in (E||x, E||y) is isotropic, whereas the directions (E||x, E||z) are anisotropic; the effect of pressure on the loss function of the deep ultraviolet region gradually increases as the pressure increases.

  11. Highly trifluoromethylated platinum compounds.

    Science.gov (United States)

    Martínez-Salvador, Sonia; Forniés, Juan; Martín, Antonio; Menjón, Babil

    2011-07-11

    The homoleptic, square-planar organoplatinum(II) compound [NBu(4)](2) [Pt(CF(3))(4)] (1) undergoes oxidative addition of CF(3) I under mild conditions to give rise to the octahedral organoplatinum(IV) complex [NBu(4)](2) [Pt(CF(3))(5)I] (2). This highly trifluoromethylated species reacts with Ag(+) salts of weakly coordinating anions in Me(2)CO under a wet-air stream to afford the aquo derivative [NBu(4)][Pt(CF(3))(5) (OH(2))] (4) in around 75% yield. When the reaction of 2 with the same Ag(+) salts is carried out in MeCN, the solvento compound [NBu(4) ][Pt(CF(3))(5)(NCMe)] (5) is obtained in around 80% yield. The aquo ligand in 4 as well as the MeCN ligand in 5 are labile and can be cleanly replaced by neutral and anionic ligands to furnish a series of pentakis(trifluoromethyl)platinate(IV) compounds with formulae [NBu(4)][Pt(CF(3))(5) (L)] (L=CO (6), pyridine (py; 7), tetrahydrothiophene (tht; 8)) and [NBu(4)](2) [Pt(CF(3))(5)X] (X=Cl (9), Br (10)). The unusual carbonyl-platinum(IV) derivative [NBu(4)][Pt(CF(3))(5) (CO)] (6) is thermally stable and has a ν(CO) of 2194 cm(-1). The crystal structures of 2⋅CH(2)Cl(2), 5, [PPh(4) ][Pt(CF(3))(5)(CO)] (6'), and 7 have been established by X-ray diffraction methods. Compound 2 has shown itself to be a convenient entry to the chemistry of highly trifluoromethylated platinum compounds. To the best of our knowledge, compounds 2 and 4-10 are the organoelement compounds with the highest CF(3) content to have been isolated and adequately characterized to date.

  12. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study.

    Science.gov (United States)

    Zhang, Lu-Ning; Gao, Yuan-Hong; Lan, Xiao-Wen; Tang, Jie; OuYang, Pu-Yun; Xie, Fang-Yun

    2015-10-01

    The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study. Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis. After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis. In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. The efficacy and safety of bevacizumab combined with chemotherapy in treatment of HER2-negative metastatic breast cancer: a meta-analysis based on published phase III trials.

    Science.gov (United States)

    Fang, Yuan; Qu, Xinlan; Cheng, Boran; Chen, Yuanyuan; Wang, Zhenmeng; Chen, Fangfang; Xiong, Bin

    2015-03-01

    Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95% confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82-1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72-36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.

  14. Comparison of Intracellular Stress Response of NCI-H526 Small Cell Lung Cancer (SCLC) Cells to Platinum(II) Cisplatin and Platinum(IV) Oxoplatin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Gerhard [Ludwig Boltzmann Cluster of Translational Oncology, A-1090 Vienna (Austria)

    2014-07-08

    In attempts to develop an orally applicable platinum-based drug, platinum(IV) drugs which exhibit higher in vivo stability compared to the platinum(II) drug cisplatin were formulated. The first such chemotherapeutic agent, namely satraplatin, failed to receive approval. In the present work, we checked the initial cellular stress response of the chemosensitive NCI-H526 small cell lung cancer (SCLC) cells by determination of the relative phosphorylation of 46 specific phosphorylation sites of 38 selected proteins in a six hours response to cisplatin (platinum(II)) or oxoplatin (platinum(IV)), respectively. Oxoplatin is considered as prodrug of cisplatin, although several findings point to differences in intracellular effects. Cisplatin induced hyperphosphorylation of p38α MAPK and AMPKα1, whereas oxoplatin treatment resulted in increased phosphorylation of a large number of signaling proteins involved in stress response/drug resistance, including JNK, GSK-3α, AMPKα1, src kinases, STATs, CHK-2 and especially focal adhesion kinase (FAK). Cisplatin exerts markedly higher cytotoxicity upon four hours short-term exposure in comparison to oxoplatin and, correspondingly, the extended initial stress response to the platinum(IV) drug oxoplatin thus is expected to increase clinical drug resistance. Induction of a substantial stress response to any prodrug of a platinum-based compound may likewise limit the effectivity of its active metabolite(s), such contributing to the failure of selected derivatized platinum complexes.

  15. Comparison of Intracellular Stress Response of NCI-H526 Small Cell Lung Cancer (SCLC Cells to Platinum(II Cisplatin and Platinum(IV Oxoplatin

    Directory of Open Access Journals (Sweden)

    Gerhard Hamilton

    2014-07-01

    Full Text Available In attempts to develop an orally applicable platinum-based drug, platinum(IV drugs which exhibit higher in vivo stability compared to the platinum(II drug cisplatin were formulated. The first such chemotherapeutic agent, namely satraplatin, failed to receive approval. In the present work, we checked the initial cellular stress response of the chemosensitive NCI-H526 small cell lung cancer (SCLC cells by determination of the relative phosphorylation of 46 specific phosphorylation sites of 38 selected proteins in a six hours response to cisplatin (platinum(II or oxoplatin (platinum(IV, respectively. Oxoplatin is considered as prodrug of cisplatin, although several findings point to differences in intracellular effects. Cisplatin induced hyperphosphorylation of p38α MAPK and AMPKα1, whereas oxoplatin treatment resulted in increased phosphorylation of a large number of signaling proteins involved in stress response/drug resistance, including JNK, GSK-3α, AMPKα1, src kinases, STATs, CHK-2 and especially focal adhesion kinase (FAK. Cisplatin exerts markedly higher cytotoxicity upon four hours short-term exposure in comparison to oxoplatin and, correspondingly, the extended initial stress response to the platinum(IV drug oxoplatin thus is expected to increase clinical drug resistance. Induction of a substantial stress response to any prodrug of a platinum-based compound may likewise limit the effectivity of its active metabolite(s, such contributing to the failure of selected derivatized platinum complexes.

  16. Platinum availability for future automotive technologies.

    Science.gov (United States)

    Alonso, Elisa; Field, Frank R; Kirchain, Randolph E

    2012-12-04

    Platinum is an excellent catalyst, can be used at high temperatures, and is stable in many aggressive chemical environments. Consequently, platinum is used in many current industrial applications, notably automotive catalytic converters, and prospective vehicle fuel cells are expected to rely upon it. Between 2005 and 2010, the automotive industry used approximately 40% of mined platinum. Future automotive industry growth and automotive sales shifts toward new technologies could significantly alter platinum demand. The potential risks for decreased platinum availability are evaluated, using an analysis of platinum market characteristics that describes platinum's geophysical constraints, institutional efficiency, and dynamic responsiveness. Results show that platinum demand for an automotive fleet that meets 450 ppm greenhouse gas stabilization goals would require within 10% of historical growth rates of platinum supply before 2025. However, such a fleet, due largely to sales growth in fuel cell vehicles, will more strongly constrain platinum supply in the 2050 time period. While current platinum reserves are sufficient to satisfy this increased demand, decreasing platinum ore grade and continued concentration of platinum supply in a single geographic area are availability risk factors to platinum end-users.

  17. Differential effect of adjuvant taxane-based and taxane-free chemotherapy regimens on the CK-19 mRNA-positive circulating tumour cells in patients with early breast cancer.

    Science.gov (United States)

    Xenidis, N; Perraki, M; Apostolaki, S; Agelaki, S; Kalbakis, K; Vardakis, N; Kalykaki, A; Xyrafas, A; Kakolyris, S; Mavroudis, D; Georgoulias, V

    2013-02-19

    To determine the effect of adjuvant taxane-free and taxane-based chemotherapy regimens on the elimination of circulating tumour cells (CTCs) in patients with early breast cancer. The presence of CK-19 mRNA-positive CTCs in the peripheral blood was evaluated before and after chemotherapy, using a real-time RT-PCR assay, in a historical comparison of two cohorts of women with stage I-III breast cancer treated with adjuvant taxane-free (N=211; FE(75)C or E(75)C) and taxane-based (N=334; T/E(75)C or T/E(75)) chemotherapy. Taxane-based chemotherapy resulted in a higher incidence of CTCs' elimination than taxane-free regimens since 49.7% (74 of 149) and 33.0% (29 of 88) of patients with detectable CTCs before chemotherapy, respectively, turned negative post-chemotherapy (P=0.015). Patients treated with taxane-free regimens had a significantly lower disease-free survival (DFS) (P=0.035) than patients treated with taxane-based regimens; this difference was observed in patients with but not without detectable CTCs before chemotherapy (P=0.018 and P=0.481, respectively). The incidence of deaths was significantly higher in the taxane-free cohort of patients with but not without detectable CTCs before chemotherapy compared with that of the taxane-based cohort (P=0.002). Multivariate analysis revealed that the chemotherapy regimen was significantly associated with prolonged DFS (HR: 2.00; 95% CI=1.20-3.34). Elimination of CK-19 mRNA-positive CTCs during adjuvant chemotherapy seems to be an efficacy indicator of treatment and is associated with a favourable clinical outcome of patients with detectable CTCs before chemotherapy.

  18. Highly efficient greenish-blue platinum-based phosphorescent organic light-emitting diodes on a high triplet energy platform

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y. L., E-mail: yilu.chang@mail.utoronto.ca; Gong, S., E-mail: sgong@chem.utoronto.ca; White, R.; Lu, Z. H., E-mail: zhenghong.lu@utoronto.ca [Department of Materials Science and Engineering, University of Toronto, 184 College St., Toronto, Ontario M5S 3E4 (Canada); Wang, X.; Wang, S., E-mail: wangs@chem.queensu.ca [Department of Chemistry, Queen' s University, 90 Bader Lane, Kingston, Ontario K7L 3N6 (Canada); Yang, C. [Department of Chemistry, Wuhan University, Wuhan 430072 (China)

    2014-04-28

    We have demonstrated high-efficiency greenish-blue phosphorescent organic light-emitting diodes (PHOLEDs) based on a dimesitylboryl-functionalized C^N chelate Pt(II) phosphor, Pt(m-Bptrz)(t-Bu-pytrz-Me). Using a high triplet energy platform and optimized double emissive zone device architecture results in greenish-blue PHOLEDs that exhibit an external quantum efficiency of 24.0% and a power efficiency of 55.8 lm/W. This record high performance is comparable with that of the state-of-the-art Ir-based sky-blue organic light-emitting diodes.

  19. 肺癌化疗患者的循证护理%Evidence-based care of patients with lung cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    李芳梅

    2010-01-01

    Objective To discuss the adverse reactions in patients with lung cancer the best nursing care. Methods 52 cases of adverse reactions in patients with lung cancer evidence-based care, to alleviate the suffering of patients caused by chemotherapy, to help address the chemotherapy-induced phlebitis, gastrointestinal reactions, bone marrow suppression, urinary tract toxicity, liver toxicity, hair loss and other side effects. Results appropriate care through effective measures to improve the health status of patients, enhance self-care ability of patients to reduce pain during chemotherapy solved chemotherapy side effects, ensure the effect of chemotherapy and the chemotherapy process.Conclusion The patients with lung cancer during chemotherapy according to different levels of side effects take corresponding measures to care not only improves the quality of care, improved quality of life of patients and reduce the suffering of patients, prolonged survival, have been dramatically enhanced the nurse Feiai chemotherapy, the theoretical knowledge and skills, while improving the overall standard of care the hospital.%目的 探讨肺癌患者不良反应的最佳护理措施.方法 对52例肺癌患者的不良反应进行循证护理,减轻患者因化疗引起的痛苦,帮助解决因化疗所致的静脉炎、肠道反应、骨髓抑制、泌尿系统毒性、肝脏毒性、脱发等副作用.结果 经过有效相应的护理措施,改善了患者的健康状况,增强了患者自我保健的能力,减轻了化疗期间的疼痛,解决了化疗药物引起的副作用,保证了化疗效果及化疗的进程.结论 根据肺癌患者化疗期间不同程度的副作用采取相对应的护理措施,不仅提高了护理质量,改善了患者的生活质量,减轻了患者的痛苦,延长了生存期,也大幅度地提高了护士对肺癌化疗的理论知识和技能,同时也提高了医院的整体护理水平.

  20. Detection of glutamate and acetylcholine with organic electrochemical transistors based on conducting polymer/platinum nanoparticle composites.

    Science.gov (United States)

    Kergoat, Loïg; Piro, Benoît; Simon, Daniel T; Pham, Minh-Chau; Noël, Vincent; Berggren, Magnus

    2014-08-27

    The aim of the study is to open a new scope for organic electrochemical transistors based on PEDOT:PSS, a material blend known for its stability and reliability. These devices can leverage molecular electrocatalysis by incorporating small amounts of nano-catalyst during the transistor manufacturing (spin coating). This methodology is very simple to implement using the know-how of nanochemistry and results in efficient enzymatic activity transduction, in this case utilizing choline oxidase and glutamate oxidase.

  1. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database

    Directory of Open Access Journals (Sweden)

    Jian-Hua Sun

    2016-04-01

    Full Text Available BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been developed to treat peritoneal carcinomatosis (PC. This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A or recurrent EOC (group B were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS and overall survival (OS; the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2 for group B (P = .68. The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5 for group B (P = .034. Better median OS correlated with peritoneal cancer index (PCI 20 group, P = .01, complete cyroreduction (residual disease ≤ 2.5 mm [79.5 months for completeness of cytoreduction (CC score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05. Serious adverse events occurred in five patients (10.0%. Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

  2. Discussion of risks of platinum resources based on a function orientated criticality assessment. Shown by cytostatic drugs and automotive catalytic converters; Diskussion der Risiken der Ressource Platin auf Basis eines um funktionale Faktoren erweiterten Kritikalitaetsassessments. Dargestellt am Beispiel platinhaltiger Zytostatika und Autoabgaskatalysatoren

    Energy Technology Data Exchange (ETDEWEB)

    Thorenz, Andrea; Reller, Armin [University of Augsburg, Chair of Resource Strategy, Environment Science Center, Augsburg (Germany)

    2011-12-15

    The purpose of the study is the enhancement of criticality assessments for resources in order to address function specific factors like dissipation, recycling, bio-activity and toxicity. The developed methodology is applied to platinum-containing cytostatic drugs and automotive catalytic converters. Methods: The study is methodically based on an analysis of resource specific factors like exploration rates, reserves-to-production ratio and regional distribution of exploration areas as well as on the investigation of product/functional depending factors like recycling rates, dissipation rates, bio-diversity and toxicity. Taking into account that economic and ecological risks may occur at any stage of the supply, consumption and dissipation processes, the whole life cycles of the two analyzed products (cytostatic drugs and automotive catalytic converters) are considered. As an approach to reduce potential economic and ecological risks the study is especially focused on recycling strategies. In order to get a better understanding of platinum as an essential resource for the dev