WorldWideScience

Sample records for cancer post gefitinib

  1. Gefitinib in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Raffaele Costanzo

    2011-01-01

    Full Text Available Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR that plays a key role in the biology of non small cell lung cancer (NSCLC. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

  2. Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Balslev, Eva; Lykkesfeldt, Anne;

    2011-01-01

    The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the Erb...

  3. Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Balslev, Eva; Lykkesfeldt, Anne;

    2011-01-01

    The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor a (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the Erb...

  4. The role of Gefitinib in patients with non-small-cell lung cancer in India

    Directory of Open Access Journals (Sweden)

    Asmita Anilkumar Mehta

    2013-01-01

    Full Text Available Background: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC. We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India. Materials and Methods: Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis. Results: The median follow-up for the cohort was 311 days (range 11-1544 days. Median time to progression was 161 (range 9-883 days. Complete and partial remission was seen in 1 (2% and 6 (9% patients, respectively, with overall response rate of 11%. Twenty-four (38% patients had stable disease. Gefitinib was well tolerated with no significant side effects. Conclusion: Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.

  5. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial

    DEFF Research Database (Denmark)

    Bernsdorf, M.; Ingvar, C.; Jorgensen, L.;

    2011-01-01

    Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown both anti-proliferative and anti-tumoral activity in breast cancer. This study was designed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide (EC) on tumor response rates. ...

  6. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  7. Massive pleural effusion and associated pulmonary embolism in a case of Gefitinib responsive lung cancer

    Directory of Open Access Journals (Sweden)

    Rajiv Garg

    2015-01-01

    Full Text Available Pulmonary embolism (PE and venous thrombosis is a common complication in lung cancer patients with a high misdiagnosis rate and high mortality. However, when an undiagnosed lung cancer patient presents as PE, cancer as a cause may not always be explored. We present a case of a young male patient presenting with venous thromboembolism causing massive pleural effusion, leading to the diagnosis of epidermal growth factor receptor mutation positive adenocarcinoma, showing good response to gefitinib therapy.

  8. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

    OpenAIRE

    Camirand, Anne; Zakikhani, Mahvash; Young, Fiona; Pollak, Michael

    2005-01-01

    Introduction Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemo...

  9. Gefitinib: a pharmacoeconomic profile of its use in patients with Non Small Cell Lung Cancer EGFR+

    Directory of Open Access Journals (Sweden)

    Viola Sacchi

    2011-06-01

    Full Text Available Lung cancer is the most common form of cancer with the highest incidence worldwide. The mortality rates are highest in males and second highest in females, after breast cancer. The genetic predisposition to Non Small Cell Lung Cancer (NSCLC is still under investigation, however, studies have shown that the Epidermal Growth Factor Receptor (EGFR, a receptor tyrosine kinase is frequently over-expressed and activated to a phosphorylated state in NSCLC. The activity of EGFR in cancer cells results in the phosphorylation of downstream proteins that promote cell proliferation, invasion, metastasis, and inhibition of apoptosis. Targeting the EGFR pathway therefore constitutes a relevant strategy for cancer therapy. Gefitinib is a selective inhibitor of the EGFR tyrosine kinase and is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK. From the pharmacoeconomic point of view gefitinib is dominant (more effective and less expensive compared to the alternatives. In conclusion, gefitinib is a treatment option for NSCLC tumors with a high clinical and economic value in the Italian setting.

  10. The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    C.L. Watkins

    2010-09-01

    Full Text Available As the first approved epidermal growth factor receptor (EGFR-targeted therapy for nonsmall cell lung cancer (NSCLC, the clinical development of gefitinib was complex. Advances in scientific understanding of the target biology during its clinical development enabled the identification of a biomarker to define patients most likely to derive benefit from gefitinib. Initial phase II trials showed clinically meaningful anti-tumour activity in 12–18% of unselected pretreated patients with advanced NSCLC at the optimum biological dose (250 mg. Subgroup analyses of these and subsequent phase III trials in unselected patients suggested that EGFR mutation and some clinical characteristics associated with a higher incidence of EGFR mutation (Asian ethnicity, adenocarcinoma histology, never-smoking and female sex were linked with increased response to gefitinib. Consequently, the IRESSA Pan-Asia Study (IPASS was conducted in never-smokers or former light-smokers in East Asia who had adenocarcinoma of the lung. IPASS showed that EGFR mutation was the strongest predictor of improved progression-free survival (mutation-positive subgroup hazard ratio (HR 0.48, 95% CI 0.36–0.64 (p<0.001, n = 261; mutation-negative subgroup HR 2.85, 95% CI 2.05–3.98 (p<0.001, n = 176; interaction test p<0.001 with gefitinib versus carboplatin/paclitaxel as first-line therapy for advanced NSCLC. Important lessons for the development of future personalised medicines are discussed.

  11. Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YUAN Guang-jin; KE Qin-hua; XU Xi-ming; YANG Ji-yuan; SU Xiao-yan

    2010-01-01

    @@ In February 2005, Gefitinib (Iressa), a small-molecular epidermal growth factor receptor and tyrosine kinase inhibitor, was approved in China as an anticancer agent for patients with advanced (local or metastatic) non-small cell lung cancer (NSCLC), who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.~1

  12. Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib-Induced Hepatotoxicity: Review of 8 Clinical Cases

    Directory of Open Access Journals (Sweden)

    Yukihiro Yano

    2012-01-01

    Full Text Available Objective. Gefitinib often induces liver damage. A few reports have described that the subsequent administration of erlotinib was associated with less hepatotoxicity, but the safety and efficacy of this treatment are still not fully investigated. Therefore, we evaluated retrospectively the patients with erlotinib following gefitinib-induced hepatotoxicity. Methods and Patients. We retrospectively reviewed the medical records between December 2007 and March 2010. The patients were evaluated including the following information: age, gender, histology of lung cancer, performance status, smoking status, epidermal growth factor receptor (EGFR mutation status, liver metastasis, viral hepatitis, alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib following gefitinib-induced hepatotoxicity. All achieved disease control by gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively. The median duration of treatment with gefitinib was 112.5 days and the median time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions. Erlotinib administration with careful monitoring is thought to be a good alternative strategy for patients who respond well to gefitinib treatment but experience hepatotoxicity.

  13. Successful treatment of EGFR-mutated non-small cell lung cancer with reduced-dose gefitinib: A case report

    OpenAIRE

    Watanabe, Hiroko; TAMURA, TOMOHIRO; KAGOHASHI, KATSUNORI; TAKAYASHIKI, NORIO; KURISHIMA, KOICHI; Satoh, Hiroaki; HIZAWA, NOBUYUKI

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutation is a favorable prognostic factor of non-small cell lung cancer (NSCLC). In the majority of patients with EGFR mutations, clinical benefits of EGFR-tyrosine kinase inhibitors (TKIs) have been reported. One of the TKIs, gefitinib, appears to be less toxic to the skin than other TKIs. The present study reports a case of NSCLC with EGFR mutation (exon 19 deletion) in which dose-reduced gefitinib was effective against recurrence. Due to development ...

  14. Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells.

    Science.gov (United States)

    Kobayashi, Isao; Takahashi, Fumiyuki; Nurwidya, Fariz; Nara, Takeshi; Hashimoto, Muneaki; Murakami, Akiko; Yagishita, Shigehiro; Tajima, Ken; Hidayat, Moulid; Shimada, Naoko; Suina, Kentaro; Yoshioka, Yasuko; Sasaki, Shinichi; Moriyama, Mariko; Moriyama, Hiroyuki; Takahashi, Kazuhisa

    2016-04-22

    Several recent studies have suggested that cancer stem cells (CSCs) are involved in resistance to gefitinib in non-small cell lung cancer (NSCLC). Oct4, a member of the POU-domain transcription factor family, has been shown to be involved in CSC properties of various cancers. We previously reported that Oct4 and the putative lung CSC marker CD133 were highly expressed in gefitinib-resistant persisters (GRPs) in NSCLC cells, and GRPs exhibited characteristic features of the CSCs phenotype. The aim of this study was to elucidate the role of Oct4 in the resistance to gefitinib in NSCLC cells with an activating epidermal growth factor receptor (EGFR) mutation. NSCLC cell lines, PC9, which express the EGFR exon 19 deletion mutation, were transplanted into NOG mice, and were treated with gefitinib in vivo. After 14-17 days of gefitinib treatment, the tumors still remained; these tumors were referred to as gefitinib-resistant tumors (GRTs). PC9-GRTs showed higher expression of Oct4 and CD133. To investigate the role of Oct4 in the maintenance of gefitinib-resistant lung CSCs, we introduced the Oct4 gene into PC9 and HCC827 cells carrying an activating EGFR mutation by lentiviral infection. Transfection of Oct4 significantly increased CD133-positive GRPs and the number of sphere formation, reflecting the self-renewal activity, of PC9 and HCC827 cells under the high concentration of gefitinib in vitro. Furthermore, Oct4-overexpressing PC9 cells (PC9-Oct4) significantly formed tumors at 1 × 10 cells/injection in NOG mice as compared to control cells. In addition, PC9-Oct4 tumors were more resistant to gefitinib treatment as compared to control cells in vivo. Finally, immunohistochemical analysis revealed that Oct4 was highly expressed in tumor specimens of EGFR-mutant NSCLC patients with acquired resistance to gefitinib. Collectively, these findings suggest that Oct4 plays a pivotal role in the maintenance of lung CSCs resistant to gefitinib in EGFR mutation

  15. Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer.

    Science.gov (United States)

    Cui, F; Wang, W; Wu, D; He, X; Wu, J; Wang, M

    2016-07-01

    Lung cancer, the most common malignancy, is still the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80 % of all lung cancers. Recent studies showed Cathepsin L (CTSL) is overexpressed in various cancerous tissues; however, the association between CTSL expression and EGFR-TKI resistance remains unknown. In this study, we investigated the expression of CTSL in lung cancer specimens and matched normal tissues by quantitative real-time PCR and IHC. The functional role of CTSL in resistant PC-9/GR cell line was investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that the level of CTSL expression was higher in NSCLC tissues compared with matched normal adjacent tissue samples, and CTSL was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking-down of CTSL in PC-9/GR cells could decrease cell proliferation and potentiate apoptosis induced by gefitinib, suggesting CTSL may contribute to gefitinib resistance in NSCLC. CTSL might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC. PMID:26474873

  16. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  17. Phase II Evaluation of Gefitinib in Patients With Newly Diagnosed Grade 4 Astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074

    International Nuclear Information System (INIS)

    Purpose: Amplification of the epidermal growth factor receptor (EGFR) gene represents one of the most frequent gene alterations in glioblastoma (GBM). In the current study, we evaluated gefitinib, a potent EGFR inhibitor, in the treatment of adults with newly diagnosed GBM. Methods and Materials: Ninety-eight patients (96 evaluable) were accrued between May 18, 2001, and August 2, 2002. All were newly diagnosed GBM patients who were clinically and radiographically stable/improved after radiation treatment (enrollment within 5 weeks of radiation completion). No prior chemotherapy was permitted. EGFR amplification/mutation, as assessed by fluorescence in situ hybridization and immunohistochemistry, was not required for treatment with gefitinib but was studied when tissues were available. Gefitinib was administered at 500 mg each day; for patients receiving dexamethasone or enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1,000 mg QD. Treatment cycles were repeated at 4-week intervals with brain magnetic resonance imaging at 8-week intervals. Results: Overall survival (OS; calculated from time of initial surgery) at 1 year (primary end point) with gefitinib was 54.2%, which was not statistically different compared with that of historical control population (48.9%, data from three previous Phase III North Central Cancer Treatment Group studies of newly diagnosed GBM patients). Progression-free survival (PFS) at 1 year post-RT (16.7%) was also not significantly different to that of historical controls (30.3%). Clinical outcome was not affected by EGFR status (amplification or vIII mutation). Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. Of note, the occurrence of drug-related adverse effects, such as loose stools was associated with improved OS. Conclusions: In our evaluation of nearly 100 patients with newly diagnosed GBM, treatment with adjuvant

  18. Gefitinib for Non-small Cell Lung Cancer: A meta Analysis

    Directory of Open Access Journals (Sweden)

    Jiwu GUO

    2011-04-01

    Full Text Available Background and objective Malignant grade and death rate are very high for non-small cell lung cancer, and gefitinib is a new molecule target anticancer drug. The aim of this meta analysis is to evaluate the clinical efficacy and safety of gefitinib for non-small cell lung cancer. Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL (The Cochrane Library, Issue 8, 2010, PubMed (1966-2010.8, EMBASE (1974-2010.8, CNKI (1994-2010.8, VIP (1989-2010.8, and CMD Digital Periodicals (1998-2010.8. Two reviewers independently evaluated the quality of the included studies and extracted the data. Meta-analyses were performed by RevMan 5.0 software. Results Thirteen randomized controlled trials (RCTs involving 6,207 patients were included. The results of meta-analyses showed that: gefitinib showed no remarkable advantage in media survival time, 1 year survival rate, complete response rate (CRR, partial response rate (PRR, stable disease (SD when compared to Placebo, Docetaxel, Cisplatin+Docetaxel, Pemetrexed. Gifitinib could increase overall survival rate compared to Docetaxel, Cisplatin+Docetaxel (RR=1.41, 95%CI: 1.10-1.80; RR=1.93, 95%: 1.26-2.94. When compared to Placebo, Docetaxel, gifitinib could improve life quality of Total-FACT-L improve rate (RR=1.42, 95%CI: 1.16-1.74; RR=1.66, 95%CI: 1.39-1.97. The major adverse event for gifitinib were rash/acne, dry skin, diarrhea. While gifitinib showed lower hematology toxicity. Conclusion Gifitinib shows more superiority for non-small cell lung cancer, and its clinical application is worthy to be advocated.

  19. Fibroblasts weaken the anti-tumor effect of gefitinib on co-cultured non-small cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yong Xiao; Wang Peiqin; Jiang Tao; Yu Wenchen; Shang Yan; Han Yiping; Zhang Pingping

    2014-01-01

    Background Non-small cell lung cancer (NSCLC) is the most common lung malignancy worldwide.The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment,which consists of tumor cells,stroma,blood vessels,immune infiltrates and the extracellular matrix.Fibroblasts can produce numerous extraceilular matrix molecules and growth factors.Gefitinib has been evaluated as a first-line treatment in selected patients,and it has shown favorable efficacy especially in NSCLC,but it is not effective for everyone.Methods In this study,we examined the antitumor activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells.A series of co-culture experiments that employed cell counting kit-8 (CCK8),transwells,real-time polymerase chain reaction (RT-PCR) and Western blotting with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to learn more about tumor cell proliferation,migration and invasion; and to determine any change of epithelial mesenchymal transition (EMT)-associated tumor markers vimentin,matrix metallopro-teinase 2 (MMP2) and chemotaxis cytokines receptor 4 (CXCR4) mRNA levels.Results A549 cell proliferation in the presence of HFL-1 cells was not significantly increased compared with A549 cells alone,but A549 cell spheroid body formation was increased after co-culture,and treatment with gefitinib increased further.Our study also revealed that fibroblasts attenuated the lung cancer cell inhibition ratio of migration and invasion after gefitinib treatment in vitro.To further study this mechanism,RT-PCR analysis showed that vimentin,MMP2 and CXCR4 mRNA levels were more highly expressed in the lung cancer cells after co-culture,but did not obviously decrease compared with the control cells following gefitinib treatment.This suggests the mechanism by which fibroblasts attenuate gefitinib-induced expression of EMT-associated tumor markers.Finally,our results demonstrated that co-culture with A549 lung

  20. Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3.

    Science.gov (United States)

    Shou, Jiawei; You, Liangkun; Yao, Junlin; Xie, Jiansheng; Jing, Jing; Jing, Zhao; Jiang, Liming; Sui, Xinbing; Pan, Hongming; Han, Weidong

    2016-08-28

    The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically prolonged the overall survival of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, but the presence of primary or acquired resistance eventually leads to therapeutic failure. Thus, how to improve the efficacy and reverse the resistance to EGFR-TKIs remains a significant challenge. In this study, we found that CsA significantly augmented the anti-cancer effect of gefitinib in EGFR-TKI-sensitive and -resistant NSCLC cells. Mechanistically, CsA promoted gefitinib-induced apoptosis through inhibition of the STAT3 pathway. Similar with the function of CsA, siRNAs against STAT3 also enhanced gefitinib-induced apoptosis in multiple lung cancer cells. Xenograft studies further demonstrated that CsA promoted the anti-cancer activity of gefitinib on lung cancer cells through inhibition of STAT3. Moreover, NSCLC patients with high levels of phosphorylated STAT3 (Y705) showed a significantly poorer therapeutic response to EGFR-TKIs. This study provides preclinical evidence that the combination of CsA or a STAT3 inhibitor with EGFR-TKIs is a promising approach to improve the efficacy of EGFR-TKIs for the treatment of patients with advanced NSCLC. PMID:27264264

  1. Randomized study of gefitinib versus pemetrexed as maintenance treatment in patients with advanced glandular non-small cell lung cancer

    OpenAIRE

    Xu, Yan-Hua; Mei, Jing-Song; Zhou, Juan

    2015-01-01

    Gefitinib was compared with pemetrexed as maintenance therapy in Patients with Advanced Glandular Non-small Cell Lung Cancer, mainly regarding clinical effect and side effect. A randomized trial of pemetrexed as study group (500 mg/m2, dl) versus gefitinib as the control group [250 mg on night 1, 250 mg on morning 2 (every day)] was conducted in 188 patients, 94 cases in each group with a therapy cycle of 21 days. In addition, the study group was also treated with folic acid, vitB12 and dexam...

  2. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

    International Nuclear Information System (INIS)

    Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas. AG1024 (an inhibitor of IGF-1R) was used with gefitinib for treatment of MDA468, MDA231, SK-BR-3, and MCF-7 breast cancer lines, which express similar levels of IGF-1R but varying levels of EGFR. Proliferation assays, apoptosis induction studies, and Western blot analyses were conducted with cells treated with AG1024 and gefitinib as single agents and in combination. Gefitinib and AG1024 reduced proliferation in all lines when used as single agents, and when used in combination revealed an additive-to-synergistic effect on cell growth inhibition. Flow cytometry measurements of cells stained with annexin V-propidium iodide and cells stained for caspase-3 activation indicated that adding an IGF-1R-targeting strategy to gefitinib results in higher levels of apoptosis than are achieved with gefitinib alone. Gefitinib either reduced or completely inhibited p42/p44 Erk kinase phosphorylation, depending on the cell line, while Akt phosphorylation was reduced by a combination of the two agents. Overexpression of IGF-1R in SK-BR-3 cells was sufficient to cause a marked enhancement in gefitinib resistance. These results indicate that IGF-1R signaling reduces the antiproliferative effects of

  3. Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Thomas K. Sin

    2016-02-01

    Full Text Available Non-small cell lung cancer (NSCLC represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.

  4. Chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer: a meta-analysis of 6844 patients

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hang; ZENG Chao; WANG Li-yang; XIE Hua; ZHOU Jin; DIAO Peng; YAO Wen-xiu

    2013-01-01

    Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC),in whom chemotherapy had failed.Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS).This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.Methods We systematically searched Medline,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major meetings for relevant literature.Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.The primary endpoints were OS and PFS.Results Of 182 relevant studies,12 were included in the final analysis,which consisted of 6844 patients with NSCLC.Overall,we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefltinib-free therapy,but this difference was not statistically significant (HR,0.92; 95% C/:0.85-1.00; P=0.051).Furthermore,gefltinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR,0.72; 95% C/ 0.60-0.87,P=0.001).Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR,2.51; 95% C/,1.67-3.78,P <0.001).Rashes,diarrhea,dry skin,pruritus,paronychia,and abnormal hepatic function were more frequent in the gefitinib therapy group.Conclusions Treatment with gefitinib had a clear effect on PFS and ORR,and it might contribute considerably to the OS.Furthermore,there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

  5. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    OpenAIRE

    Zhu Jun; Li Te; Wang Xiaohui; Ye Ming; Cai Jian; Xu Yuejuan; Wu Bin

    2013-01-01

    Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with ad...

  6. Randomized Phase II Study of Gefitinib Compared With Placebo in Chemotherapy-Naive Patients With Advanced Non–Small-Cell Lung Cancer and Poor Performance Status

    Science.gov (United States)

    Goss, Glenwood; Ferry, David; Wierzbicki, Rafal; Laurie, Scott A.; Thompson, Joyce; Biesma, Bonne; Hirsch, Fred R.; Varella-Garcia, Marileila; Duffield, Emma; Ataman, Ozlem U.; Zarenda, Marc; Armour, Alison A.

    2009-01-01

    Purpose To compare gefitinib with placebo in chemotherapy naïve patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status. Patients and Methods NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. Results Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. Conclusion There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors. PMID:19289623

  7. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm3) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a combination

  8. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J., E-mail: anderson.ryan@oncology.ox.ac.uk

    2014-03-15

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm{sup 3}) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a

  9. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bersanelli, Melissa, E-mail: melissa.bersanelli@alice.it; Buti, Sebastiano; Camisa, Roberta [Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy); Brighenti, Matteo; Lazzarelli, Silvia [Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona (Italy); Mazza, Giancarlo [Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia (Italy); Passalacqua, Rodolfo, E-mail: melissa.bersanelli@alice.it [1Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy)

    2014-09-30

    The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m{sup 2} (Million International Unit/m{sup 2})twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  10. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Melissa Bersanelli

    2014-09-01

    Full Text Available The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group. The other 31 also received subcutaneous IL-2 (GIL-2 group: 1 MIU/m2 (Million International Unit/m2twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%, asthenia/anorexia (6% and diarrhea (7%; patients treated with IL-2 showed grade 2–3 fever (46%, fatigue (21% and arthralgia (13%. In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response and 5.1% (only partial response; a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8 and 4.1 (CI 95% = 2.6–5.7 months; a median overall survival of 20.1 (CI 95% = 5.1–35.1 and 6.9 (CI 95% = 4.9–8.9 months (p = 0.002; and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54 and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60 were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  11. EGFR mutations in patients with brain metastases from lung cancer: Association with the efficacy of gefitinib

    OpenAIRE

    Shimato, Shinji; Mitsudomi, Tetsuya; Kosaka, Takayuki; Yatabe, Yasushi; Wakabayashi, Toshihiko; Mizuno, Masaaki; NAKAHARA, NORIMOTO; Hatano, Hisashi; Natsume, Atsushi; Ishii, Dai; YOSHIDA, Jun

    2006-01-01

    Gefitinib—a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase—has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluat...

  12. Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan

    International Nuclear Information System (INIS)

    Whole brain irradiation (WBRT) either with or without resection has historically been the treatment for brain metastases from non-small cell lung cancer (NSCLC). The effect of gamma knife (GK) radiosurgery, chemotherapy, or the combination remains incompletely defined. In this study, we assessed the outcome of brain metastases from non-small cell lung cancer treated by WBRT followed by GK, gefitinib, or the combination of GK and gefitinib. We retrieved the records of NSCLC patients with brain metastases from the National Health Insurance Research Database (NHIRD) of Taiwan from 2004 to 2010. WBRT either with or without resection was the first line treatment for nearly all patients. The decision to add GK and/or gefitinib treatment was at the discretion of the treating physician and based upon a patient’s medical records and imaging data. These patients were classified into four groups including WBRT, WBRT + gefitinib, WBRT + GK, WBRT + gefitinib + GK. These data was evaluated for difference in survival and factors that portended an extended survival from the time of brain metastasis diagnosis. Of the 60194 patients with newly diagnosed NSCLC, 23874 (39.6 %) developed brain metastases. The distribution of patients for the groups was WBRT for 20241, WBRT + gefitinib for 3379, WBRT + GK for 155, and WBRT+ gefitinib + GK for 99 patients. The median survival for the time of brain metastasis diagnosis for WBRT, WBRT+ gefitinib, WBRT+ GK, WBRT+ gefitinib + GK groups was 0.53, 1.01, 1.46, and 2.25 years, respectively (p < 0.0001). The hazard ratio (95 % CI) for survival was 1, 0.56, 0.43, and 0.40, respectively (p < 0.001). The adjusted hazard ratio (95 % CI) by age, sex and Charlson comorbidity index (CCI) was 1, 0.73, 0.49, and 0.42, respectively (p < 0.001). Patients with brain metastases from NSCLC receiving GK or gefitinib demonstrated extended survival. The improved survival seen with GK and gefitinib suggests a survival benefit in selected patients receiving the

  13. CT findings in non-small-cell lung cancer patients treated with gefitinib or erlotinib

    Directory of Open Access Journals (Sweden)

    Im Il Na

    2012-01-01

    Full Text Available Purpose: We performed this study to explore the association of computed tomography (CT findings with outcomes of patients with non-small-cell lung cancer (NSCLC treated with tyrosin kinase inhibitor (TKI such as gefitinib or erlotinib. Materials and Methods: We analyzed outcomes for 240 patients according to primary tumor (T, regional nodal (N staging and diffuse small pulmonary metastases (DSPM at the initial presentation. Tests for epidermal growth factor receptor (EGFR mutation were performed in 92 patients. Results: On multivariate analysis for tumor response, the N3 stage was predictive of a poor response (P < 0.001, whereas DSPM was a favorable factor (P = 0.007. Multivariate analysis for progression-free survival showed that the T3-4 stage (hazard ratio [HR]: 2.5, P < 0.001, in addition to the N3 stage (HR: 2.1, P < 0.001, was predictive of a poor outcome, whereas DSPM (HR: 0.6, P = 0.006 was a favorable factor. Notably, the multivariate model that included the EGFR mutational status revealed that the T3-4 stage predicted poor progression-free survival (HR: 2.2, P = 0.017 and poor overall survival (HR: 4.1, P < 0.001. Conclusion: Our data suggest that, in addition to EGFR mutational status, T-stage based on CT is predictive of outcomes of TKI-treated NSCLC patients.

  14. Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

    International Nuclear Information System (INIS)

    Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2nd EGFR-TKI administration. We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment. Three patients (27%) were treated with gefitinib as the 2nd EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2nd EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2nd EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2nd EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy. Our results indicate that a 2nd EGFR-TKI treatment can be an effective treatment option for gefitinib responders

  15. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    International Nuclear Information System (INIS)

    Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option

  16. In vivo evaluation of P-glycoprotein and breast cancer resistance protein modulation in the brain using [{sup 11}C]gefitinib

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: kawamur@nirs.go.jp; Yamasaki, Tomoteru; Yui, Joji; Hatori, Akiko; Konno, Fujiko; Kumata, Katsushi; Irie, Toshiaki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Kanno, Iwao; Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2009-04-15

    Gefitinib (Iressa) is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Recent studies confirmed that gefitinib interacted with the breast cancer resistance protein (BCRP) at submicromolar concentrations, whereas other multidrug transporters, including P-glycoprotein (P-gp), showed much lower reactivity toward gefitinib. Recently, many tracers for positron emission tomography (PET) have been prepared to study P-gp function in vivo; however, PET tracers had not been evaluated for both P-gp and BCRP modulation in the brain. Therefore, we evaluated in vivo brain penetration-mediated P-gp and BCRP in mice using [{sup 11}C]gefitinib. Co-injection with gefitinib (over 50 mg/kg), a nonspecific P-gp modulator cyclosporin A (50 mg/kg), and the dual P-gp and BCRP modulator GF120918 (over 5 mg/kg) induced an increase in the brain uptake of [{sup 11}C]gefitinib in mice 30 min after injection. In the PET study of mice, the radioactivity level in the brain with co-injection of GF120918 (5 mg/kg) was three- to fourfold higher than that in control after initial uptake. The radioactivity level in the brain in P-gp and Bcrp knockout mice was approximately eightfold higher than that in wild-type mice 60 min after injection. In conclusion, [{sup 11}C]gefitinib is a promising PET tracer to evaluate the penetration of gefitinib into the brain by combined therapy with P-gp or BCRP modulators, and into brain tumors. Furthermore, PET study with GF120918 is a promising approach for evaluating brain penetration-mediated P-gp and BCRP.

  17. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    Directory of Open Access Journals (Sweden)

    Zhu Jun

    2013-01-01

    Full Text Available Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER at a willingness-to-pay (WTP threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP was evaluated. Results After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP. The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. Conclusions These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

  18. In vivo evaluation of P-glycoprotein and breast cancer resistance protein modulation in the brain using [11C]gefitinib

    International Nuclear Information System (INIS)

    Gefitinib (Iressa) is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Recent studies confirmed that gefitinib interacted with the breast cancer resistance protein (BCRP) at submicromolar concentrations, whereas other multidrug transporters, including P-glycoprotein (P-gp), showed much lower reactivity toward gefitinib. Recently, many tracers for positron emission tomography (PET) have been prepared to study P-gp function in vivo; however, PET tracers had not been evaluated for both P-gp and BCRP modulation in the brain. Therefore, we evaluated in vivo brain penetration-mediated P-gp and BCRP in mice using [11C]gefitinib. Co-injection with gefitinib (over 50 mg/kg), a nonspecific P-gp modulator cyclosporin A (50 mg/kg), and the dual P-gp and BCRP modulator GF120918 (over 5 mg/kg) induced an increase in the brain uptake of [11C]gefitinib in mice 30 min after injection. In the PET study of mice, the radioactivity level in the brain with co-injection of GF120918 (5 mg/kg) was three- to fourfold higher than that in control after initial uptake. The radioactivity level in the brain in P-gp and Bcrp knockout mice was approximately eightfold higher than that in wild-type mice 60 min after injection. In conclusion, [11C]gefitinib is a promising PET tracer to evaluate the penetration of gefitinib into the brain by combined therapy with P-gp or BCRP modulators, and into brain tumors. Furthermore, PET study with GF120918 is a promising approach for evaluating brain penetration-mediated P-gp and BCRP.

  19. The Mechanism of Gefitinib Resistance Induced by Hepatocyte Growth Factor 
in Sensitive Non-small Cell Lung Cancer Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Xianglan XUAN

    2013-01-01

    Full Text Available Background and objective Previous studies have reported that Met might be related to gefitinib resistance in non-small cell lung cancer (NSCLC. The present study aims to explore the mechanism of hepatocyte growth factor (HGF-induced gefitinib resistance in different gene types of sensitive NSCLC in vitro. Methods The PC-9 and H292 cell lines were chosen and induced by HGF. The cell survival was measured using MTT assay, the cell cycle distribution was measured using PI assay, and cell apoptosis with an Annexin V-PE assay, respectively. The c-Met and p-Met protein expression was determined via Western blot analysis. Results Gefitinib inhibited the growth of PC-9 and H292 cells in a dose-dependent manner. The concentration-survival curves of both cell lines shifted to the right when induced with HGF. HGF did not affect PC-9 and H292 cell proliferation. The cell also had a higher cell survival rate when treated with HGF and gefitinib compared with that under gefitinib alone (P<0.05. The apoptotic rate and cell cycle progression showed no significant difference between the HG and G group (P>0.05. HGF stimulated Met phosphorylation in the PC-9 and H292 cells. Gefitinib inhibited the HGF-induced Met phosphorylation in PC-9 cells, but not in H292 cells. Conclusion HGF induces gefitinib resistance in PC-9 and H292 cells. HGF-induced Met phosphorylation may be an important mechanism of gefitinib resistance in sensitive NSCLC.

  20. A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. Methods and Materials: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1α (IL-1α), and IL-6 in serum. Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

  1. Response to gefitinib and erlotinib in Non-small cell lung cancer: a retrospective study

    International Nuclear Information System (INIS)

    In Non-small cell lung cancer (NSCLC), an overactive epidermal growth factor receptor (EGFR) pathway is a component of the malignant phenotype. Two tyrosine kinase inhibitors (TKIs) of EGFR, gefinitib and erlotinib, have been used with variable benefit. We have analyzed outcome data of a population of NSCLC patients that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response. Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated (phosphorylated) members of the pathway, pEGFR, pERK, pAKT, and pSTAT3. Erlotinib was slightly superior to gefitinib in all measures of response, although the differences were not statistically significant. The most robust clinical predictors of time to progression (TTP) were best response and rash (p < 0.0001). A higher level of pEGFR was associated with longer TTP, while the total EGFR level was not associated with response. Higher levels of pAKT and pSTAT3 were also associated with longer TTP. In contrast, a higher level of pERK1/2 was associated with shorter TTP. These observations suggest the hypothesis that tumor cells that have activated EGFR pathways, presumably being utilized for survival, are clinically relevant targets for pathway inhibition. An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway. TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT, and little pERK. In the absence of molecular predictors of response, the appearance of a rash and a positive first scan are good clinical indicators of response

  2. Gefitinib, an epidermal growth factor receptor blockade agent, shows additional or synergistic effects on the radiosensitivity of esophageal cancer cells in vitro

    International Nuclear Information System (INIS)

    Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGER-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 μM to 36.9 μM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy. (author)

  3. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  4. Down-regulation of ERK1/2 and AKT-mediated X-ray repair cross-complement group 1 protein (XRCC1) expression by Hsp90 inhibition enhances the gefitinib-induced cytotoxicity in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Jian, Yi-Jun [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Department of Biochemical Science and Technology, National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan (China); Syu, Jhan-Jhang; Wang, Tai-Jing; Chang, Po-Yuan; Chen, Chien-Yu; Jian, Yun-Ting [Department of Biochemical Science and Technology, National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan (China); Lin, Yun-Wei, E-mail: linyw@mail.ncyu.edu.tw [Department of Biochemical Science and Technology, National Chiayi University, 300 Syuefu Road, Chiayi 600, Taiwan (China)

    2015-05-15

    Gefitinib (Iressa{sup R}, ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. It has been shown that inhibition of Hsp90 function can enhance antitumor activity of EGFR-TKI. XRCC1 is an important scaffold protein in base excision repair, which could be regulated by ERK1/2 and AKT pathways. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in gefitinib alone or combination with an Hsp90 inhibitor-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. In this study, gefitinib treatment decreased XRCC1 mRNA and protein expression through ERK1/2 and AKT inactivation in two NSCLC cells, A549 and H1975. Knocking down XRCC1 expression by transfection with small interfering RNA of XRCC1 enhanced the cytotoxicity and cell growth inhibition of gefitinib. Combining treatment of gefitinib with an Hsp90 inhibitor resulted in enhancing the reduction of XRCC1 protein and mRNA levels in gefitinib-exposed A549 and H1975 cells. Compared to a single agent alone, gefitinib combined with an Hsp90 inhibitor resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors rescued the XRCC1 protein level as well as the cell survival suppressed by an Hsp90 inhibitor and gefitinib. These findings suggested that down-regulation of XRCC1 can enhance the sensitivity of gefitinib for NSCLC cells. - Highlights: • Gefitinib treatment decreased XRCC1 mRNA and protein expression in NSCLC cells. • Knocking down XRCC1 expression enhanced the cytotoxic effect of gefitinib. • Gefitinib combined with an Hsp90 inhibitor resulted in synergistically cytotoxicity.

  5. Down-regulation of ERK1/2 and AKT-mediated X-ray repair cross-complement group 1 protein (XRCC1) expression by Hsp90 inhibition enhances the gefitinib-induced cytotoxicity in human lung cancer cells

    International Nuclear Information System (INIS)

    Gefitinib (IressaR, ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that blocks growth factor-mediated cell proliferation and extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT signaling activation. It has been shown that inhibition of Hsp90 function can enhance antitumor activity of EGFR-TKI. XRCC1 is an important scaffold protein in base excision repair, which could be regulated by ERK1/2 and AKT pathways. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in gefitinib alone or combination with an Hsp90 inhibitor-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. In this study, gefitinib treatment decreased XRCC1 mRNA and protein expression through ERK1/2 and AKT inactivation in two NSCLC cells, A549 and H1975. Knocking down XRCC1 expression by transfection with small interfering RNA of XRCC1 enhanced the cytotoxicity and cell growth inhibition of gefitinib. Combining treatment of gefitinib with an Hsp90 inhibitor resulted in enhancing the reduction of XRCC1 protein and mRNA levels in gefitinib-exposed A549 and H1975 cells. Compared to a single agent alone, gefitinib combined with an Hsp90 inhibitor resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors rescued the XRCC1 protein level as well as the cell survival suppressed by an Hsp90 inhibitor and gefitinib. These findings suggested that down-regulation of XRCC1 can enhance the sensitivity of gefitinib for NSCLC cells. - Highlights: • Gefitinib treatment decreased XRCC1 mRNA and protein expression in NSCLC cells. • Knocking down XRCC1 expression enhanced the cytotoxic effect of gefitinib. • Gefitinib combined with an Hsp90 inhibitor resulted in synergistically cytotoxicity

  6. The role of repair protein Rad51 in synergistic cytotoxicity and mutagenicity induced by epidermal growth factor receptor inhibitor (Gefitinib, IressaR) and benzo[a]pyrene in human lung cancer

    International Nuclear Information System (INIS)

    Rad51 protein is essential for homologous recombination repair of DNA damage, and is over-expressed in chemo- or radioresistant carcinomas. The polycyclic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) affects MAPKs transduction pathways. Gefitinib (IressaR, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks growth factor-mediated cell proliferation and ERK1/2 activation. We hypothesized that gefitinib enhances B[a]P-mediated cytotoxicity by decreasing ERK1/2 activation. Exposure of human lung cancer cells to gefitinib decreased B[a]P-elicited ERK1/2 activation and induced Rad51 protein expression. Gefitinib and B[a]P co-treatment decreased Rad51 protein stability by triggering degradation via a 26S proteasome-dependent pathway. Expression of constitutive active MKK1/2 vectors (MKK1/2-CA) rescues the decreased ERK1/2 activity, and restores Rad51 protein level and stability under gefitinib and B[a]P co-treatment. Gefitinib enhances B[a]P-induced growth inhibition, cytotoxicity and mutagenicity. Co-treatment with gefitinib and B[a]P can further inhibit cell growth significantly after depletion of endogenous Rad51 by siRad51 RNA transfection. Enhancement of ERK1/2 activation by MKK1-CA expression decrease B[a]P- and gefitinib-induced cytotoxicity, and B[a]P-induced mutagenicity. Rad51 protein protects lung cancer cells from synergistic cytotoxic and mutagenic effects induced by gefitinib and B[a]P. Suppression of Rad51 protein expression may be a novel lung cancer therapeutic modality to overcome drug resistance to gefitinib

  7. Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib (IressaTM) and to the antiangiogenic agent ZD6474: Cytotoxic and biomolecular effects

    Institute of Scientific and Technical Information of China (English)

    Amalia Azzariti; Letizia Porcelli; Jian-Ming Xu; Grazia Maria Simone; Angelo Paradiso

    2006-01-01

    AIM: To analyze the biological effects of prolonged in vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib (Iressa TM), an inhibitor of epidermal growth factor receptor (EGFR) activity, and ZD6474, an inhibitor of both KDR and EGFR activities. METHODS: Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent (4 d of drug exposure followed by 3 d of washout each week) schedule.RESULTS: In both cell types, prolonged exposure (up to 14 d) to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erk1/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. CONCLUSION: We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.

  8. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

    DEFF Research Database (Denmark)

    Kim, E.S.; Hirsh, V.; Mok, T.;

    2008-01-01

    %]); whereas in the docetaxel group, neutropenia (35 [5%] vs 514 [74%]), asthenic disorders (182 [25%] vs 334 [47%]), and alopecia (23 [3%] vs 254 [36%]) were most common. INTERPRETATION: INTEREST established non-inferior survival of gefitinib compared with docetaxel, suggesting that gefitinib is a valid...

  9. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Directory of Open Access Journals (Sweden)

    Chunxiang Zhang

    Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  10. Phase II trial of sequential gefitinib after minor response or partial response to chemotherapy in Chinese patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhao Chuan

    2006-12-01

    Full Text Available Abstract Background Basic research of gefitinib (Iressa, ZD1839 has demonstrated the combination effects of gefitinib and chemotherapy were sequence-dependent. To evaluate the efficacy of sequential administration of gefitinib following a minor response or partial response to two to three cycles of chemotherapy, a phase II clinical trial was done in Chinese patients with advanced non-small-cell lung cancer (NSCLC. Methods Thirty-three consecutive patients with advanced NSCLC that had been pretreated with at least one chemotherapeutic regimen and were responding to chemotherapy following 2 to 3 cycles of treatment, entered the trial from May 2004 to February 2006. Patients received gefitinib at an oral dose of 250 mg once daily for 4 weeks. Results Thirty-three patients were evaluable for response and toxicity. The objective response rate was 24.2% (8 of 33(95% CI, 11% to 42%. The symptom improvement rate was 54.5% (18 of 33 (95% CI, 41% to 69%. The median duration of response was 7 months (95%CI, 4.0 to 13.2 months. The median time to disease progression (TTP was 6.5 months (95%CI, 0.7 to 16.6 months. The median overall survival time (OS was 9.8 months (range, 2.1 to 18.0 months, and the actuarial 1-year survival was 36.4%. Toxicity was relatively mild and included only one patient (3.0% with grade 4 diarrhea, 1 (3.0% with grade 3 rash, 1 (3.0% with grade 3 nausea, and 1 with grade 3 vomiting (3.0%. Conclusion Preliminary results suggest that sequential administration of gefitinib following a response to chemotherapy may be beneficial for Chinese patients with advanced NSCLC. Further randomized clinical trials are needed.

  11. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China

    Science.gov (United States)

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Background Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Methods Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Results Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. Conclusions The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market. PMID:27015267

  12. Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines

    International Nuclear Information System (INIS)

    EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination

  13. Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Hong, Dongsheng; Zhang, Guobing; Zhang, Xingguo; Lian, Xingguang

    2016-03-01

    Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear.The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients.Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies.According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%-0.99%), 2.33% (95% CI: 1.47%-3.66%), 2.24% (95% CI: 1.34%-3.72%), and 1.43% (95% CI: 0.98%-2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46-6.52; P = 0.42), 0.99 (95% CI: 0.66-1.49; P = 0.95), 4.70 (95% CI: 1.48-14.95; P = 0.0087), and 2.64 (95% CI: 1.22-5.69; P = 0.01), respectively.Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug. PMID:26945426

  14. Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

    OpenAIRE

    Satouchi, M; Negoro, S; Funada, Y; Urata, Y.; Shimada, T; Yoshimura, S.; Kotani, Y.; Sakuma, T.; Watanabe, H.(Max-Planck-Institut für Kernphysik, 69117, Heidelberg, Germany); Adachi, S.; Takada, Y.; Y. Yatabe; Mitsudomi, T.

    2007-01-01

    This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day−1) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epider...

  15. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Jie Huang; Shu-Xiang Ma; Xue Hou; Zhao Wang; Yin-Duo Zeng; Tao Qin; Xiao-Xiao Dinglin; Li-Kun Chen

    2015-01-01

    Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinical y characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

  16. Elevated expression level of laminin 5 may be a negative predictive factor for the response to gefitinib in lung cancer patients%层粘连蛋白5高表达可能是肺癌患者吉非替尼疗效差的预测因子

    Institute of Scientific and Technical Information of China (English)

    Shejuan An; Jianquan Zhu; Zhihong Chen; Guochun Zhang; Zhen Wang; Yilong Wu

    2008-01-01

    Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog-enous LN5 and gefitinib to A549 lung cancer cell line, and Westem-blotting was performed to investigate the phosphorylation level of EGFR, Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut-point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib.In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.

  17. Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Zhu, XinHai; Jiang, Hao; Li, Jinhui; Xu, Ji; Fei, Zhenghua

    2016-01-01

    BACKGROUND Paris saponins have been studied for their anticancer effects in various cancer types, but the mechanisms underlying the cytotoxic effects, especially in EGFR-TKI-resistant cells, are still unclear. We explored the potential mechanism of the antitumor effects of PSI, II, VI, VII in EGFR-TKI-resistant cells and attempted to develop PSI, II, VI, VII as a systemic treatment strategy for EGFR-TKI-resistant lung cancer. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The apoptosis assay was detected using annexin-V/PI and Hoechst staining. The level of PI3K, pAKT, Bax, Bcl-2, caspase-3, and caspase-9 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI, II, VI, VII inhibited the proliferation of PC-9-ZD cells. Furthermore, PSI, II, VI, VII induced significant cell apoptosis. The levels of PI3K, pAKT, Bcl-2 protein decreased, while the Bax, caspase-3, and caspase-9 protein was increased by PSI, II, PSVI, PSVII treatment and resulted in increased sensitivity to gefitinib in PC-9-ZD cells. CONCLUSIONS The underlying mechanism of Paris saponins may be related to targeting the PI3K/AKT pathways to cause apoptosis. Our results suggest a therapeutic potential of Paris saponins in clinical settings for gefitinib-resistant NSCLC. PMID:27125283

  18. Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib.

    Directory of Open Access Journals (Sweden)

    Darrell C Bessette

    Full Text Available Basal-like and triple negative breast cancer (TNBC share common molecular features, poor prognosis and a propensity for metastasis to the brain. Amplification of epidermal growth factor receptor (EGFR occurs in ~50% of basal-like breast cancer, and mutations in the epidermal growth factor receptor (EGFR have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung cancer several different mutations in the EGFR tyrosine kinase domain confer sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic potential of EGFR mutations in breast cells and their potential for targeted therapy is unknown.Constructs containing wild type, G719S or E746-A750 deletion mutant forms of EGFR were transfected into the MCF10A breast cells and their tumorigenic derivative, MCF10CA1a. The effects of EGFR over-expression and mutation on proliferation, migration, invasion, response to gefitinib, and tumour formation in vivo was investigated. Copy number analysis and whole exome sequencing of the MCF10A and MCF10CA1a cell lines were also performed.Mutant EGFR increased MCF10A and MCF10CA1a proliferation and MCF10A gefitinib sensitivity. The EGFR-E746-A750 deletion increased MCF10CA1a cell migration and invasion, and greatly increased MCF10CA1a xenograft tumour formation and growth. Compared to MCF10A cells, MCF10CA1a cells exhibited large regions of gain on chromosomes 3 and 9, deletion on chromosome 7, and mutations in many genes implicated in cancer.Mutant EGFR enhances the oncogenic properties of MCF10A cell line, and increases sensitivity to gefitinib. Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more tumourigenic in vivo it is not accompanied by increased gefitinib sensitivity, perhaps due to additional mutations, including the PIK3CA H1047R mutation, that the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for EGFR mutations may prove useful for directing therapy but, as in non

  19. Clinical Response to Gefitinib Retreatment of Lung Adenocarcinoma Patients Who Benefited from An Initial Gefitinib Therapy: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Junling LI

    2012-01-01

    Full Text Available Background and objective Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI that has been widely used for the treatment of non-small cell lung cancer (NSCLC. It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. Methods The clinical data of 18 patients with NSCLC who had shown partial response (PR or achieved a stable disease (SD status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Results Of the 18 patients studied, 1 (6% showed partial remission (PR, 11 (61% achieved SD, and 6 (33% experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months. The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months. Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months. Mild toxicity was observed with the 2nd gefitinib therapy. Conclusion The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.

  20. Evaluation of safety and efficacy of gefitinib ('iressa', zd1839) as monotherapy in a series of Chinese patients with advanced non-small-cell lung cancer: experience from a compassionate-use programme

    International Nuclear Information System (INIS)

    The gefitinib compassionate-use programme has enabled >39,000 patients worldwide to receive gefitinib ('Iressa', ZD1839) treatment. This paper reports the outcome of gefitinib treatment in Chinese patients who enrolled into the 'Iressa' Expanded Access Programme (EAP) at the Peking Union Medical College Hospital. Thirty-one patients with advanced or metastatic non-small-cell lung cancer (NSCLC) that had progressed after prior systemic chemotherapy were eligible to receive oral gefitinib 250 mg/day as part of the EAP. Treatment was continued until disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13). Gefitinib was well tolerated. Adverse events (AEs) were generally mild (grade1 and 2) and reversible. The most frequent AEs were acneform rash and diarrhoea. Only one patient withdrew from the study due to a drug-related AE. The objective tumour response rate was 35.5% (95% confidence interval [CI]: 18.6–52.3); median progression-free survival was 5.5 months (95% CI, 1.6 to 9.4); median overall survival was 11.5 months (95% CI, 5.6 to 17.3). The QoL response rates for five functioning scales and global QoL varied from 56–88%. The main symptom response rates varied from 44–84%. QoL and symptom response were correlated with objective tumour response. Gefitinib demonstrated safety and efficacy as monotherapy in this series of Chinese patients with advanced NSCLC and was also associated with remarkable symptom relief and improvement in QoL. Although clinical trials are needed to confirm these positive findings, the data suggest that treatment with gefitinib may be beneficial for some Chinese patients who do not respond to chemotherapy and have poor prognosis

  1. Evaluation of safety and efficacy of gefitinib ('iressa', zd1839 as monotherapy in a series of Chinese patients with advanced non-small-cell lung cancer: experience from a compassionate-use programme

    Directory of Open Access Journals (Sweden)

    Wang Shu-Lan

    2004-08-01

    Full Text Available Abstract Background The gefitinib compassionate-use programme has enabled >39,000 patients worldwide to receive gefitinib ('Iressa', ZD1839 treatment. This paper reports the outcome of gefitinib treatment in Chinese patients who enrolled into the 'Iressa' Expanded Access Programme (EAP at the Peking Union Medical College Hospital. Methods Thirty-one patients with advanced or metastatic non-small-cell lung cancer (NSCLC that had progressed after prior systemic chemotherapy were eligible to receive oral gefitinib 250 mg/day as part of the EAP. Treatment was continued until disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life (QoL was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13. Results Gefitinib was well tolerated. Adverse events (AEs were generally mild (grade1 and 2 and reversible. The most frequent AEs were acneform rash and diarrhoea. Only one patient withdrew from the study due to a drug-related AE. The objective tumour response rate was 35.5% (95% confidence interval [CI]: 18.6–52.3; median progression-free survival was 5.5 months (95% CI, 1.6 to 9.4; median overall survival was 11.5 months (95% CI, 5.6 to 17.3. The QoL response rates for five functioning scales and global QoL varied from 56–88%. The main symptom response rates varied from 44–84%. QoL and symptom response were correlated with objective tumour response. Conclusion Gefitinib demonstrated safety and efficacy as monotherapy in this series of Chinese patients with advanced NSCLC and was also associated with remarkable symptom relief and improvement in QoL. Although clinical trials are needed to confirm these positive findings, the data suggest that treatment with gefitinib may be beneficial for some Chinese patients who do not respond to chemotherapy and have poor prognosis.

  2. Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-11

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Parathyroid Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus

  3. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    OpenAIRE

    Wang, Ziping; Guo, Jihong; Wang, Yan; Yutao LIU; Juan YANG

    2011-01-01

    Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC) patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variable...

  4. Integrin beta 1 enhances the epithelial-mesenchymal transition in association with gefitinib resistance of non-small cell lung cancer.

    Science.gov (United States)

    Ju, Lixia; Zhou, Caicun

    2013-01-01

    We have previously shown that integrinβ1 associates with gefitinib resistance. As epithelial-mesenchymal transition (EMT) also induces gefitinib resistance in vitro, we wished to determine the relation of them in gefitinib resistance. In this study, we show that integrinβ1 induced epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in xenograft tumors and gefitinib-resistant NSCLC tumors acquired EMT phenotype. Furthermore, inhibition of integrinβ1 reverses EMT, meanwhile overexpression and activation of integrinβ1 aggravates EMT. Lastly, we further identified that integrinβ1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrinβ1 and EMT in EGFR TKI resistant NSCLC. PMID:24440972

  5. A Novel Pharmacodynamic Approach to Assess and Predict Tumor Response to the Epidermal Growth Factor Receptor Inhibitor Gefitinib in Patients with Esophageal Cancer

    OpenAIRE

    Altiok, Soner; Mezzadra, Heather; Jagannath, Sanjay; Tsottles, Nancy; Rudek, Michelle A.; Abdallah, Nadia; Berman, David; Forastiere, Arlene; Gibson, Michael K.

    2010-01-01

    This study aimed to describe a short term ex vivo assay to predict response to epidermal growth factor receptor (EGFR) targeted therapy (gefitinib) in adenocarcinoma patients. Four patients with locally advanced esophageal adenocarcinoma were treated with gefitinib (250 mg/day) for 14 days and pharmacokinetic (PK) studies were conducted to monitor plasma drug concentrations. Tumor cells were sampled by endoscopic biopsy prior to (baseline, day 0) and at the completion of (day 14) treatment. C...

  6. Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non-small-cell lung cancer.

    Science.gov (United States)

    Hayashi, Hideki; Kita, Yutaro; Iihara, Hirotoshi; Yanase, Koumei; Ohno, Yasushi; Hirose, Chiemi; Yamada, Maya; Todoroki, Kenichiro; Kitaichi, Kiyoyuki; Minatoguchi, Shinya; Itoh, Yoshinori; Sugiyama, Tadashi

    2016-07-01

    A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 μL samples of human blood plasma. Diluted plasma samples were extracted using a liquid-phase extraction procedure with tert-butyl methyl ether. The three drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05-100 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall-cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC-MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26525154

  7. EGFR-independent autophagy induction with gefitinib and enhancement of its cytotoxic effect by targeting autophagy with clarithromycin in non-small cell lung cancer cells.

    Science.gov (United States)

    Sugita, Shohei; Ito, Kentaro; Yamashiro, Yutaro; Moriya, Shota; Che, Xiao-Fang; Yokoyama, Tomohisa; Hiramoto, Masaki; Miyazawa, Keisuke

    2015-05-22

    Gefitinib (GEF), an inhibitor for EGFR tyrosine kinase, potently induces autophagy in non-small cell lung cancer (NSCLC) cell lines such as PC-9 cells expressing constitutively activated EGFR kinase by EGFR gene mutation as well as A549 and H226 cells with wild-type EGFR. Unexpectedly, GEF-induced autophagy was also observed in non-NSCLC cells such as murine embryonic fibroblasts (MEF) and leukemia cell lines K562 and HL-60 without EGFR expression. Knockout of EGFR gene in A549 cells by CRISPR/Cas9 system still exhibited autophagy induction after treatment with GEF, indicating that the autophagy induction by GEF is not mediated through inhibiting EGFR kinase activity. Combined treatment with GEF and clarithromycin (CAM), a macrolide antibiotic having the effect of inhibiting autophagy flux, enhances the cytotoxic effect in NSCLC cell lines, although treatment with CAM alone exhibits no cytotoxicity. GEF treatment induced up-regulation of endoplasmic reticulum (ER)-stress related genes such as CHOP/GADD153 and GRP78. Knockdown of CHOP in PC-9 cells and Chop-knockout MEF both exhibited less sensitivity to GEF than controls. Addition of CAM in culture medium resulted in further pronounced GEF-induced ER stress loading, while CAM alone exhibited no effect. These data suggest that GEF-induced autophagy functions as cytoprotective and indicates the potential therapeutic possibility of using CAM for GEF therapy. Furthermore, it is suggested that the intracellular signaling for autophagy initiation in response to GEF can be completely dissociated from EGFR, but unknown target molecule(s) of GEF for autophagy induction might exist. PMID:25858318

  8. Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Chien-Ming Liu

    2015-01-01

    Full Text Available Introduction. Epidermal growth factor receptor (EGFR mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells and A549 (EGFR wild type; Gefitinib-resistant cells cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.

  9. Progressive multiple cystic changes in both lungs in a patient treated with gefitinib for lung adenocarcinoma with multiple lung metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Yon Ju; Chun, Eun Mi; Lee, Soon Nam; Shim, Sung Shin [Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2014-04-15

    Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

  10. Ephedrae herba stimulates hepatocyte growth factor-induced MET endocytosis and downregulation via early/late endocytic pathways in gefitinib-resistant human lung cancer cells.

    Science.gov (United States)

    Nishimura, Yukio; Hyuga, Sumiko; Takiguchi, Soichi; Hyuga, Masashi; Itoh, Kazuyuki; Hanawa, Toshihiko

    2016-05-01

    The MET tyrosine kinase receptor and its ligand, hepatocyte growth factor (HGF), are known to be overexpressed in a variety of malignant tumor cells, and are implicated in the development of gefitinib-resistance in human non-small cell lung cancer (NSCLC) cells. Ephedrae herba was previously reported to prevent HGF-induced cancer cell motility by directly suppressing HGF/MET signaling through the inhibition of MET tyrosine kinase, and treatment with its extract also considerably reduced MET protein levels. To further investigate the mechanism underlying the Ephedrae herba-induced inhibition of MET phosphorylation as well as its degradation and subsequent disappearance, we examined the effect of Ephedrae herba on HGF-stimulated MET endocytosis and downregulation via early/late endocytic pathways in an NSCLC cell line. Using immunofluorescence microscopy, we found that pretreatment of cells with Ephedrae herba extract dramatically changed the intracellular distribution of plasma membrane-associated MET, and that the resultant MET staining was distributed throughout the cytoplasm. Pretreatment of the cells with Ephedrae herba extract also led to the rapid loss of MET and phosphorylated (p)-MET in HGF-stimulated cells. In contrast, inefficient endocytic delivery of MET and p-MET from early to late endosomes was observed in the absence of Ephedrae herba extract, since considerable amounts of the internalized MET accumulated in the early endosomes and were not delivered to lysosomes up to 1 h after HGF-stimulation. Furthermore, large amounts of MET and p-MET that had accumulated in late endosomes of Ephedrae herba-pretreated cells after HGF stimulation were observed along with bafilomycin A1. Therefore, we inferred that degradation of MET occurred in the late endosome/lysosome pathway. Moreover, western blot analysis revealed the accelerated degradation of MET and p-MET proceeds in cells pretreated with Ephedrae herba extract. Collectively, our results suggest that

  11. Systemic Nocardiosis Mimicking Disease Flare-up after Discontinuation of Gefitinib in a Patient with EGFR-Mutant Lung Cancer

    OpenAIRE

    Choi, Mihong; Lee, Youngjoo; Hwang, Sang Hyun; Lee, Jin Soo

    2014-01-01

    Disease flare-up after discontinuing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung cancer patients who have experienced radiologic progression after showing initial durable response. This is a case of systemic nocardiosis that occurred after chronic steroid use for radionecrosis from stereotactic radiosurgery. It was initially thought as a disease flare-up after stopping EGFR-TKI.

  12. Progress in Clinical Studies of the Gefitinib Uesd in the Treatment of Non-small cell lung cancer(NSCLC)%吉非替尼治疗非小细胞肺癌的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    戴青; 马荔

    2014-01-01

    Lung cancer is the most common cause of death,85%of non-small cell lung cancer,and most patients with advanced performance,generating 5-year rate was 1%~5%.In recent years,successfully developed tyrosine ki-nase inhibitors,opened a new era of smallmolecule targeted cancer therapy.Especially the Gefitinib which is devel-oped and launched by Astra Zeneca,provides another effective treatment for patients with advanced NSCLC.This pa-per gived an overview of worldwide clinical studies of Gefitinib in the treatment of non-small cell lung cancer,which included the monotherapy of Gefitinib in first-line, second-line and maintenance treatment, also the combination chemotherapy in non-small cell lung cancer.%肺癌是肿瘤死亡的最常见原因,其中85%为非小细胞肺癌,且大多数患者有晚期的表现,患者5年的生成率仅为1%~5%,近年研发成功的酪氨酸激酶抑制剂,开启了肿瘤小分子靶向治疗的新时代,尤其是由阿斯利康公司研制并推出的吉非替尼,为晚期 NSCLC患者又提供了一种有效的治疗药物。本文对吉非替尼治疗非小细胞肺癌的临床研究进展进行综述,其中包括全球范围内吉非替尼单药二线、一线和维持治疗,以及联合化疗治疗非小细胞肺癌的临床研究进展。

  13. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  14. Auto-synthesis of 11C-gefitinib and micro PET/CT imaging for A549

    International Nuclear Information System (INIS)

    Gefitinib is an approved anticancer drug inhibiting epidermal growth factor receptor/tyrosine kinase (EGFR/TK) in non-small cell lung cancer (NSCLC). In this work, we aimed at developing an auto-synthesis method for 11C-Gefitinib with 11C-CH3-Triflate as methylation agent, and evaluating 11C-Gefinitib to explore its specific uptake with micro PET imaging, 11C-Gefitinib was synthesized by the reaction of 7-demethyl precursor with 11C-CH3-Triflate under base condition, and purified by HPLC. Micro PET/CT imaging was performed in A549 tumor-bearing mice. The results showed that it took 28 min for synthesis of 11C-Gefitinib with radiochemical yields of 30%-35% (with decay correction, n>5). The radiochemical purity was over 99%, and the specific activity was 55.5 GBq/μmol, respectively. Micro PET/CT imaging showed that the A549 tumor uptake of 11C-Gefitinib could be blocked by co-injection of non-radioactive Gefitinib (50 mg/kg), demonstrating the tumor specific accumulation of 11C-Gefitinib. It is concluded that 11C-Gefitinib can be served as PET imaging agent for the evaluation of Gefinitib therapy in NSCLC. (authors)

  15. Comparison of different methods for detecting epidermal growth factor receptor mutations in peripheral blood and tumor tissue of non-small cell lung cancer as a predictor of response to gefitinib

    Directory of Open Access Journals (Sweden)

    Xu F

    2012-12-01

    Full Text Available Fei Xu,1,* Jingxun Wu,2,* Cong Xue,1,* Yuanyuan Zhao,1 Wei Jiang,3 Liping Lin,4 Xuan Wu,5 Yachao Lu,6 Hua Bai,7 Jiasen Xu,8 Guanshan Zhu,6 Li Zhang11State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People's Republic of China; 3Department of Medical Oncology, Cancer Hospital of Guangxi Medical University and Guangxi Autonomous Regional Cancer Hospital, Nanning, Guangxi, People's Republic of China; 4Department of Oncology and Hemotology, Panyu Central Hospital, Guangzhou, Guangdong, People's Republic of China; 5Department of Chemotherapy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China; 6Innovation Center China, AstraZeneca Global R&D, Shanghai, People's Republic of China; 7Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China; 8SurExam Bio-Tech Co, Ltd, Science City, Guangzhou, People's Republic of China *These authors contributed equally to this workBackground: Previous studies have reported that epidermal growth factor receptor (EGFR mutation in tumor tissue and peripheral blood can predict the response to EGFR tyrosine kinase inhibitor (TKI in non-small cell lung cancer (NSCLC. However, the heterogeneity of the sample sources makes it difficult to evaluate the detecting methodologies. The goal of this study is to compare different methods for analyzing EGFR mutation in blood and tumor tissue.Materials and methods: Fifty-one advanced NSCLC patients treated with gefitinib were included in the study. The EGFR mutation status of each patients' blood was analyzed by denaturing high-performance liquid chromatography (DHPLC, mutant-enriched liquidchip (ME-Liquidchip, and Scorpion

  16. Molecular and Clinical Responses in a Pilot Study of Gefitinib With Paclitaxel and Radiation in Locally Advanced Head-and-Neck Cancer

    International Nuclear Information System (INIS)

    Purpose: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT). Methods and Materials: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age ≥18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGFR signaling, tumor cell proliferation, and apoptosis in biopsy samples. Results: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m2 intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated EGFR, decreased downstream signaling, and reduced cellular proliferation after initiating GEF. Conclusions: Inhibition of EGFR by GEF was observed in only one of seven tumors studied. The addition of GEF to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis.

  17. Gefitinib

    Science.gov (United States)

    ... dissolved. Drink the mixture right away. Rinse the glass with another 4 to 8 ounces (120 to ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  18. Enediyne lidamycin enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, in epidermoid carcinoma A431 cells and lung carcinoma H460 cells.

    Science.gov (United States)

    Liu, Hong; Li, Liang; Li, Xing-Qi; Liu, Xiu-Jun; Zhen, Yong-Su

    2009-01-01

    Gefitinib, a low-molecular-weight epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective in a wide variety of tumor types. Preclinical studies have shown potentiated antitumor efficacies of this agent in combination with chemotherapy or radiotherapy. The antitumor antibiotic lidamycin (LDM) showed extremely potent cytotoxicity in vitro and marked therapeutic effect in vivo. In this report, the cytotoxic and biochemical activity of LDM and gefitinib on human epidermoid carcinoma A431 cells and human large cell lung cancer H460 cells as a single agent or in combination has been evaluated. In the MTT assay, LDM showed much more potent cytotoxicity than gefitinib to both cell lines. A431 cells with a highly EGFR-expressing level were more sensitive to gefitinib than H460 cells, which expressed EGFR at an intermediate level. LDM plus gefitinib showed potentiation of antiproliferative activity and apoptosis induction, which were associated with downregulation of EGFR signaling pathway and nuclear factor-kappa B expression, and the increase of cleaved poly (adenosine diphosphate-ribose) polymerase in the two cell lines, although to a lesser degree in H460 cells. Combined treatment induced G1 phase arrest similar to that of gefitinib alone in A431 cells and intensified G2/M phase accumulation in H460 cells. The above results indicate that LDM potentiates the effects of gefitinib in both gefitinib sensitive and less sensitive cells in association with enhanced inhibition of EGFR-dependent signaling. PMID:19342999

  19. Screening for breast cancer post reduction mammoplasty

    International Nuclear Information System (INIS)

    Aim: To investigate whether remodelling of the breast after breast reduction surgery has an effect on mammographic cancer detection. Methods and materials: For women who attended population-based screening between January 1998 to December 2007, data were extracted on their age, history of previous breast reduction, and the result of screening (recall for further assessment, cancer, or no cancer). The number of cancers detected, recalls per 1000 screens and the characteristics of the cancers detected in the two groups was compared. Results: In total 244,147 women with 736,219 screening episodes were reviewed. In the 4743 women who had a breast reduction, 51 breast cancers were detected [age standardized rate (ASR) of 4.28 per 1000 screening episodes; 95% CI 3.11-5.46], compared with 4342 breast cancers in 239 404 women screened in the non-reduction group (ASR of 5.99 per 1000 screening episodes; 95% CI 5.81-6.16). There were fewer cancers in the breast reduction group with a relative risk of 0.71. There was no significant difference in the rate of recall between the two groups, with a crude recall rate of 46.1 per 1000 screening episodes post-breast reduction compared with 50.7 per 1000 screening episodes for women without breast reduction. There was no significant difference in the pathological type or location of the cancer between the two groups of women. Conclusion: Postoperative breast changes following reduction mammoplasty do not significantly hinder analysis of the screening mammogram.

  20. Randomized double-blind trial of prophylactic topical Evozac® Calming Skin Spray for gefitinib-associated acne-like eruption

    OpenAIRE

    Wang Y; Yang Y; Xu J; Yu J; Liu X; Gao R.; Zhang L.

    2014-01-01

    Yalan Wang,* Yunpeng Yang,* Jinxia Xu, Juan Yu, Xia Liu, Ruizhen Gao, Li Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China *These authors contributed equally to this work Background: "Gefitinib" is a first-generation epidermal growth factor receptor tyrosine-kinase inhibitor. More than half of patients receiving gefitinib develop acne...

  1. Randomized double-blind trial of prophylactic topical Evozac® Calming Skin Spray for gefitinib-associated acne-like eruption

    OpenAIRE

    Zhang, Li

    2014-01-01

    Yalan Wang,* Yunpeng Yang,* Jinxia Xu, Juan Yu, Xia Liu, Ruizhen Gao, Li Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China *These authors contributed equally to this work Background: "Gefitinib" is a first-generation epidermal growth factor receptor tyrosine-kinase inhibitor. More than half of patients receiving gefitinib ...

  2. RTOG 0211: A Phase 1/2 Study of Radiation Therapy With Concurrent Gefitinib for Newly Diagnosed Glioblastoma Patients

    International Nuclear Information System (INIS)

    Purpose: To determine the safety and efficacy of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with radiation for newly diagnosed glioblastoma (GBM) patients. Methods and Materials: Between March 21, 2002, and May 3, 2004, Radiation Therapy Oncology Group (RTOG) 0211 enrolled 31 and 147 GBM patients in the phase 1 and 2 arms, respectively. Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy (RT) and continued post RT for 18 months or until progression. Tissue microarrays from 68 cases were analyzed for EGFR expression. Results: The maximum tolerated dose (MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs (non-EIAEDs). All patients in the phase 2 component were treated at a gefitinib dose of 500 mg; patients receiving EIADSs could be escalated to 750 mg. The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal. Median survival was 11.5 months for patients treated per protocol. There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone, matched by RTOG recursive partitioning analysis (RPA) class distribution. Younger age was significantly associated with better outcome. Per protocol stratification, EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients. Conclusions: The addition of gefitinib to RT is well tolerated. Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone

  3. RTOG 0211: A Phase 1/2 Study of Radiation Therapy With Concurrent Gefitinib for Newly Diagnosed Glioblastoma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarti, Arnab, E-mail: Arnab.chakravarti@osumc.edu [Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University, Columbus, Ohio (United States); Wang, Meihua [Radiation Therapy Oncology Group (RTOG) Statistical Center, Philadelphia, Pennsylvania (United States); Robins, H. Ian [University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin (United States); Lautenschlaeger, Tim [Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University, Columbus, Ohio (United States); Curran, Walter J. [Department of Neurosurgery, University of Toronto, Toronto, Ontario, Canada, and Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Brachman, David G. [Department of Radiation Oncology, Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Schultz, Christopher J. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Choucair, Ali [Neuroscience Institute, Norton Healthcare System, Louisville, Kentucky (United States); Dolled-Filhart, Marisa [HistoRx, Branford, Connecticut (United States); Christiansen, Jason [Department of Neurological Surgery, University of California–San Francisco, San Francisco, California (United States); Gustavson, Mark [HistoRx, Branford, Connecticut (United States); Molinaro, Annette [HistoRx, Branford, Connecticut (United States); Ludwig Institute for Cancer Research, University of California–San Diego, La Jolla, California (United States); Mischel, Paul [Ludwig Institute for Cancer Research, University of California–San Diego, La Jolla, California (United States); Dicker, Adam P. [Radiation Oncology Department, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); and others

    2013-04-01

    Purpose: To determine the safety and efficacy of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with radiation for newly diagnosed glioblastoma (GBM) patients. Methods and Materials: Between March 21, 2002, and May 3, 2004, Radiation Therapy Oncology Group (RTOG) 0211 enrolled 31 and 147 GBM patients in the phase 1 and 2 arms, respectively. Treatment consisted of daily oral gefinitnib started at the time of conventional cranial radiation therapy (RT) and continued post RT for 18 months or until progression. Tissue microarrays from 68 cases were analyzed for EGFR expression. Results: The maximum tolerated dose (MTD) of gefitinib was determined to be 500 mg in patients on non-enzyme-inducing anticonvulsant drugs (non-EIAEDs). All patients in the phase 2 component were treated at a gefitinib dose of 500 mg; patients receiving EIADSs could be escalated to 750 mg. The most common side effects of gefitinib in combination with radiation were dermatologic and gastrointestinal. Median survival was 11.5 months for patients treated per protocol. There was no overall survival benefit for patients treated with gefitinib + RT when compared with a historical cohort of patients treated with RT alone, matched by RTOG recursive partitioning analysis (RPA) class distribution. Younger age was significantly associated with better outcome. Per protocol stratification, EGFR expression was not found to be of prognostic value for gefitinib + RT-treated patients. Conclusions: The addition of gefitinib to RT is well tolerated. Median survival of RTOG 0211 patients treated with RT with concurrent and adjuvant gefitinib was similar to that in a historical control cohort treated with radiation alone.

  4. p300/CBP dependent hyperacetylation of histone potentiates anticancer activity of gefitinib nanoparticles.

    Science.gov (United States)

    Kaur, Jasmine; Tikoo, Kulbhushan

    2013-05-01

    Gefitinib is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor, approved for patients with non-small cell lung cancer (NSCLC). In this report we demonstrate that gefitinib loaded PLGA nanoparticles (GNPs), in comparison to gefitinib, exhibited higher anti-cancer activity on A549 lung carcinoma cells and A431 skin carcinoma cells. Increased inhibition of pEGFR in both the cell types explains its higher anti-cancer activity. Interestingly, gefitinib resistant, H1975 (T790M EGFR mutant) lung carcinoma cells was also found to be sensitive to GNPs. Our data shows that GNPs hyperacetylate histone H3 in these cells, either directly or indirectly, which may account for the augmented cell death. GNPs were proficient in activating histone acetyltransferases (p300/CBP), which in turn induces the expression of p21 and cell cycle arrest. Furthermore, inhibition of histone acetyltransferases by garcinol results in alleviation of cell death caused by GNPs. In addition to this, nuclear intrusion of GNPs results in the inhibition of NO production in nucleus, possibly through nuclear EGFR, which might be responsible for preventing cell proliferation in resistant cells. To best of our knowledge, we provide first evidence that GNPs potentiate cell death by activating p300/CBP histone acetyltransferases. PMID:23384777

  5. Docetaxel as salvage chemotherapy in patients with advanced non-small cell lung cancer after failure of cytotoxic agents and gefitinib treatment%晚期非小细胞肺癌化疗和靶向治疗失败后的挽救性化疗

    Institute of Scientific and Technical Information of China (English)

    Yilong Wu; Jinji Yang; Yujuan Huang; Qin Zhou; Yisheng Huang; Chongrui Xu

    2008-01-01

    Objective:We conducted a prospective phase Ⅱ trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting.Methods:Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m2 intravenously for 30 min every 3 weeks until the toxicity was unacceptable or disease progressed.The response evaluation criteria in solid tumors (RECIST) guidelines were used for the evaluation of antitumor activity.Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0.Results:In total,31 patients were enrolled in this phase Ⅱ trial between February 2004 and December 2006,and 84 cycles (average 2.7 cycles) were given.We observed 4 partial responses (PRs) and 10 stable disease (SD) states in 31 eligible patients.The objective response rate was 12.9%,and the disease control rate was 45.2%.The median survival time (MST) was 10 months (95% Cl,5.05-15.08 months).The 1-year survival rate was 40.6%.The most common toxicities were neutropenia,anemia,and peripheral neuropathy that occurred as follows:45% of the patients experienced grade 3 or 4 neutropenia,29% experienced grade 3 anemia,and 25.8% had grade 3 peripheral neuropathy.No patient terminated docetaxel chemotherapy due to toxicity.Conclusion:Docetaxei is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.

  6. Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yoshiko; Aoki, Takatoshi; Korogi, Yukunori [University of Occupational and Environmental Health, School of Medicine, Department of Radiology, Kitakyushu (Japan); Hanagiri, Takeshi; Uramoto, Hidetaka [University of Occupational and Environmental Health, School of Medicine, Second Department of Surgery, Kitakyushu (Japan); Yoshii, Chiharu; Mukae, Hiroshi [University of Occupational and Environmental Health, School of Medicine, Department of Respiratory Disease, Kitakyushu (Japan)

    2012-04-15

    To assess the frequency of osteosclerotic changes on CT that appeared after treatment with gefitinib in patients with lung adenocarcinoma and the relationship between the osteosclerotic changes and the response to the therapy. Our study included 41 patients with lung adenocarcinoma who underwent chest CT both before (CTpre) and after (CTpost) starting treatment with gefitinib. The presence or absence of bone metastases was assessed on the CTpre, and the interval bony change after the therapy was classified as lytic, sclerotic, or no changes on the CTpost. The relationship between treatment results of primary lung cancer and interval bony changes was evaluated. Osteosclerotic lesions were identified in 11 patients (27%) on CTpost; in 6 of 11 patients osteosclerotic lesions newly appeared where the CTpre showed no bone metastasis before the gefitinib therapy. There were significant differences in the therapeutic response of the primary cancers (P < 0.001) and in the survival rate (P < 0.01) in patients with osteosclerotic changes versus those without osteosclerotic changes. Osteosclerotic changes on CT, observed after gefitinib treatment in patients with lung adenocarcinomas, may be an indicator of a good therapeutic response. (orig.)

  7. Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response

    International Nuclear Information System (INIS)

    To assess the frequency of osteosclerotic changes on CT that appeared after treatment with gefitinib in patients with lung adenocarcinoma and the relationship between the osteosclerotic changes and the response to the therapy. Our study included 41 patients with lung adenocarcinoma who underwent chest CT both before (CTpre) and after (CTpost) starting treatment with gefitinib. The presence or absence of bone metastases was assessed on the CTpre, and the interval bony change after the therapy was classified as lytic, sclerotic, or no changes on the CTpost. The relationship between treatment results of primary lung cancer and interval bony changes was evaluated. Osteosclerotic lesions were identified in 11 patients (27%) on CTpost; in 6 of 11 patients osteosclerotic lesions newly appeared where the CTpre showed no bone metastasis before the gefitinib therapy. There were significant differences in the therapeutic response of the primary cancers (P < 0.001) and in the survival rate (P < 0.01) in patients with osteosclerotic changes versus those without osteosclerotic changes. Osteosclerotic changes on CT, observed after gefitinib treatment in patients with lung adenocarcinomas, may be an indicator of a good therapeutic response. (orig.)

  8. NF-κB-driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance.

    Science.gov (United States)

    Chiu, Ching-Feng; Chang, Yi-Wen; Kuo, Kuang-Tai; Shen, Yu-Shiuan; Liu, Chien-Ying; Yu, Yang-Hao; Cheng, Ching-Chia; Lee, Kang-Yun; Chen, Feng-Chi; Hsu, Min-Kung; Kuo, Tsang-Chih; Ma, Jui-Ti; Su, Jen-Liang

    2016-05-01

    Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib or erlotinib) significantly prolongs survival time for patients with tumors harboring an activated mutation on EGFR; however, up to 40% of lung cancer patients exhibit acquired resistance to EGFR-TKIs with an unknown mechanism. FOXO3a, a transcription factor of the forkhead family, triggers apoptosis, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we observed that a high level of FOXO3a was correlated with EGFR mutation-independent EGFR-TKI sensitivity, the suppression of cancer stemness, and better progression-free survival in lung cancer patients. The suppression of FOXO3a obviously increased gefitinib resistance and enhanced the stem-like properties of lung cancer cells; consistent overexpression of FOXO3a in gefitinib-resistant lung cancer cells reduced these effects. Moreover, we identified that miR-155 targeted the 3'UTR of FOXO3a and was transcriptionally regulated by NF-κB, leading to repressed FOXO3a expression and increased gefitinib resistance, as well as enhanced cancer stemness of lung cancer in vitro and in vivo. Our findings indicate that FOXO3a is a significant factor in EGFR mutation-independent gefitinib resistance and the stemness of lung cancer, and suggest that targeting the NF-κB/miR-155/FOXO3a pathway has potential therapeutic value in lung cancer with the acquisition of resistance to EGFR-TKIs. PMID:27091996

  9. Effectiveness of gefitinib in combination with methotrexate in the treatment of ectopic pregnancy

    Directory of Open Access Journals (Sweden)

    Capmas P

    2015-07-01

    Full Text Available Perrine Capmas,1 Hervé Fernandez21Inserm, Centre of Research in Epidemiology and Population Health (CESP, 2Department of Gynecology, Bicetre Hospital, GHU Sud, AP-HP, Le Kremlin Bicêtre, FranceAbstract: Medical management for ectopic pregnancy is subject to substantial variations with different protocols and various routes of administration. Regardless the protocol used, methotrexate is currently the medical treatment of choice for ectopic pregnancy. The risk of a rescue surgery is a main concern. Recently, some studies suggested combining gefitinib and methotrexate to improve medical treatment and to decrease the need for reinjection and for additional surgery. Gefitinib is an orally administered EGF receptor-tyrosine kinase inhibitor. For tubal ectopic pregnancy, median recovery time was shorter after combination treatment with gefitinib and methotrexate. Toxicity reported with combination treatment was acneiform rash in 67% of cases and diarrhea in 42%. They were always transient and are known side effects of gefitinib previously described in lung cancer. These preliminary results are very promising but need to be explored further before wide distribution. For ectopic pregnancy, combining treatment seems to be interesting but results of the first randomized trial have to be evaluated first. For other indications, such as non-tubal ectopic pregnancy or choriocarcinoma, randomized studies are needed before wide use of the combination in current practice.Keywords: toxicity, efficacy, EGF receptor-tyrosine kinase inhibitor, non-tubal ectopic pregnancy

  10. The in vitro effect of gefitinib ('Iressa' alone and in combination with cytotoxic chemotherapy on human solid tumours

    Directory of Open Access Journals (Sweden)

    Knight Louise A

    2004-11-01

    Full Text Available Abstract Background Activation of the epidermal growth factor receptor (EGFR triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa' is an orally active tyrosine kinase inhibitor (TKI targeted to the ATP-binding domain of EGFR (HER1; erbB1. Methods In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan against a variety of solid tumours (n = 86, including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI at each test drug concentration (TDC. Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml. This study represents the first use of a TKI in the assay. Results There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86 of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76 of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45 had a >50% decrease in their IndexSUM. In 38% of tumours (29/76, the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76 there was no

  11. Prognostic potential of initial CT changes for progression-free survival in gefitinib-treated patients with advanced adenocarcinoma of the lung: a preliminary analysis

    International Nuclear Information System (INIS)

    We aimed to determine whether initial tumour responses measured during short-term follow-up computed tomography (CT) examinations after baseline examinations would correlate with clinical outcomes in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)-targeted therapy. A total of 86 gefitinib-treated patients with advanced adenocarcinoma of the lung were retrospectively reviewed. All patients underwent baseline and short-term follow-up CT examinations. The new response criteria (NRC) by Lee et al. were used for the response evaluations. A Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses were used to evaluate correlations between the initial tumour changes and progression-free and overall survival (PFS, OS). Better separation and smaller p values were observed for both PFS and OS when good and poor disease responses (as defined by NRC) were compared after excluding tumours with characteristic morphologies. Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a stronger association was observed between size changes and PFS when characteristic morphology was also considered. Initial changes in tumour size during short-term post-treatment CT examinations could act as a potential prognostic imaging surrogate for PFS in gefitinib-treated patients with advanced adenocarcinoma of the lung. (orig.)

  12. Prognostic potential of initial CT changes for progression-free survival in gefitinib-treated patients with advanced adenocarcinoma of the lung: a preliminary analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yu-Cheng; Hsu, Hsian-He; Chang, Wei-Chou; Ko, Kai-Hsiung; Hsu, Yi-Chih [Tri-Service General Hospital, National Defense Medical Center, Department of Radiology, Taipei (China); Tung, Ho-Jui [Asia University, Department of Healthcare Administration, Taichung (China); Huang, Tsai-Wang; Chang, Hung [Tri-Service General Hospital, National Defense Medical Center, Division of Thoracic Surgery, Department of Surgery, Taipei (China); Ho, Ching-Liang [Tri-Service General Hospital, National Defense Medical Center, Division of hematology-oncology, Department of internal Medicine, Taipei (China)

    2015-06-01

    We aimed to determine whether initial tumour responses measured during short-term follow-up computed tomography (CT) examinations after baseline examinations would correlate with clinical outcomes in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)-targeted therapy. A total of 86 gefitinib-treated patients with advanced adenocarcinoma of the lung were retrospectively reviewed. All patients underwent baseline and short-term follow-up CT examinations. The new response criteria (NRC) by Lee et al. were used for the response evaluations. A Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses were used to evaluate correlations between the initial tumour changes and progression-free and overall survival (PFS, OS). Better separation and smaller p values were observed for both PFS and OS when good and poor disease responses (as defined by NRC) were compared after excluding tumours with characteristic morphologies. Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a stronger association was observed between size changes and PFS when characteristic morphology was also considered. Initial changes in tumour size during short-term post-treatment CT examinations could act as a potential prognostic imaging surrogate for PFS in gefitinib-treated patients with advanced adenocarcinoma of the lung. (orig.)

  13. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  14. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK

  15. Assessment of early changes in 3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate whether early changes in 3′-deoxy-3′-3H-fluorothymidine (3H-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of 3H-FLT and 18F-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of 3H-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 ± 0.09, 0.36 ± 0.06, 0.59 ± 0.11%ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of 18F-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 ± 2.4%, 6.2 ± 1.8%, and 10.4 ± 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group

  16. Radiation myelitis after hypofractionated radiotherapy with concomitant gefitinib

    International Nuclear Information System (INIS)

    We describe the case of a 71-year-old Caucasian female with primary disseminated non-small cell cancer of the lung, presented for palliative radiotherapy of metastatic spread to the 9th and 11th thoracic vertebrae without intramedullary growth. Palliative radiotherapy with daily fractions of 3 Gy and a cumulative dose of 36 Gy to thoracic vertebrae 8-12 was performed. The patient received concomitantly 250 mg gefitinib daily. After a latent period of 16 months, the patient developed symptoms of myelitis. Magnetic resonance imaging (MRI) did not reveal any bony or intraspinal tumor progression, but spinal cord signal alteration. No response to steroids was achieved. The neurological symptoms were progressive in August 2013 with the right leg being completely plegic. The left leg was incompletely paralyzed. Deep and superficial sensitivity was also diminished bilaterally. The patient was completely urinary and anally incontinent. Contrary to the clinical findings, a follow-up MRI (July 2013) showed amelioration of the former signal alterations in the spinal cord. The diagnosis of paraneoplastic myelopathy was refuted by a negative test for autologous antibodies. At the last clinical visit in May 2014, the neurological symptoms were stable. The last tumor-specific treatment the patient is receiving is erlotinib 125 mg/d. We reviewed the literature and found no reported cases of radiation myelopathy after the treatment in such a setting. The calculated probability of such complication after radiotherapy alone is statistically measurable at the level of 0.02%. We suppose that gefitinib could also play a role in the development of this rare complication

  17. European randomized lung cancer screening trials: Post NLST

    DEFF Research Database (Denmark)

    Field, JK; Klaveren, R; Pedersen, JH;

    2013-01-01

    Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects of their ......Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects...

  18. Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

    OpenAIRE

    Liu, Yutao; Shi, Yuankai; Hu, Xingsheng; Hao, Xuezhi; Li, Junling; Wang, Ziping; Yan WANG; Wang, Hongyu; Xiangru ZHANG; Sun, Yan

    2014-01-01

    Background and objective Lung cancer in young patients (less or equal to 45 years) is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR) gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 w...

  19. Pneumothorax triggered by the combination of gefitinib and amrubicin and treated with endobronchial silicone spigots

    Directory of Open Access Journals (Sweden)

    Fumio Imamura

    2015-01-01

    Full Text Available Pneumothorax is a rare complication in cancer chemotherapy. We report a case in which a male patient with advanced non-small cell lung cancer (NSCLC developed repetitive pneumothorax after receiving a combination of the chemotherapeutic drugs gefitinib and amrubicin (GEF + AMR. Both episodes of pneumothorax occurred on the 3rd day of GEF + AMR administration. Tube thoracostomy was performed, but pulmonary air leaks persisted in the second pneumothorax. Whereas surgical intervention was not applicable because of poor respiratory reserve, the chest tube was successfully removed by endoscopic occlusion of bronchopleural fistula with endobronchial Watanabe spigots (EWSs, a type of silicone bronchial blocker.

  20. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain.

    Directory of Open Access Journals (Sweden)

    William Pao

    2005-03-01

    Full Text Available BACKGROUND: Lung adenocarcinomas from patients who respond to the tyrosine kinase inhibitors gefitinib (Iressa or erlotinib (Tarceva usually harbor somatic gain-of-function mutations in exons encoding the kinase domain of the epidermal growth factor receptor (EGFR. Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance. METHODS AND FINDINGS: We show that in two of five patients with acquired resistance to gefitinib or erlotinib, progressing tumors contain, in addition to a primary drug-sensitive mutation in EGFR, a secondary mutation in exon 20, which leads to substitution of methionine for threonine at position 790 (T790M in the kinase domain. Tumor cells from a sixth patient with a drug-sensitive EGFR mutation whose tumor progressed on adjuvant gefitinib after complete resection also contained the T790M mutation. This mutation was not detected in untreated tumor samples. Moreover, no tumors with acquired resistance had KRAS mutations, which have been associated with primary resistance to these drugs. Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib. Interestingly, a mutation analogous to T790M has been observed in other kinases with acquired resistance to another kinase inhibitor, imatinib (Gleevec. CONCLUSION: In patients with tumors bearing gefitinib- or erlotinib-sensitive EGFR mutations, resistant subclones containing an additional EGFR mutation emerge in the presence of drug. This observation should help guide the search for more effective therapy against a specific subset of lung cancers.

  1. AB008. Management of fertility post cancer

    Science.gov (United States)

    Smith, James

    2016-01-01

    The successful treatment of males with cancer has led to increasing numbers of men and boys interested in life after cancer. One of the top priorities for many of these males is the opportunity to have a family. Most cancer treatments used for common malignancies in men and boys are associated with impaired fertility; for patients receiving alkylating agents or total body irradiation, severe fertility impairment occurs in most patients. While sperm banking for males, even those as young as 12, facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination to achieve a pregnancy. Most males would prefer to restore their natural ability to father children and avoid these expensive and invasive approaches. No proven method for human male fertility restoration has yet been demonstrated; however, work in many mammalian species and recently in primates has demonstrated that autologous testicular cell transplant (TCT) can restore spermatogenesis after cancer treatment. Promising work in non-primate species has demonstrated the feasibility of in vitro development of mature sperm from neonatal testicular tissue. The safety and efficacy of either approach has not been established in humans. The objective of this lecture is to explore current and future fertility preservation and restoration techniques for males at risk of sterility from medical and surgical treatment.

  2. The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours

    International Nuclear Information System (INIS)

    Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1). In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml). This study represents the first use of a TKI in the assay. There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86) of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76) of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45) had a >50% decrease in their IndexSUM). In 38% of tumours (29/76), the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76) there was no change observed. The in vitro

  3. Proliferation of Ewing sarcoma cell lines is suppressed by the receptor tyrosine kinase inhibitors gefitinib and vandetanib

    Directory of Open Access Journals (Sweden)

    Åman Pierre

    2008-01-01

    Full Text Available Abstract Background Tyrosine kinase inhibitors (TKIs have gained much attention in recent years as targeted agents for the treatment of a wide range of human cancers. We have investigated the effect of the TKIs gefitinib and vandetanib on tumor cell lines derived from Ewing sarcoma, a highly malignant tumor affecting bone and soft tissue in children and young adults. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR and vandetanib selectively targets vascular endothelial growth factor receptor-2 (VEGFR-2 with additional activity against VEGFR-3, EGFR and RET kinase receptors. Results Two Ewing sarcoma cell lines investigated showed high levels of nuclear EGFR expression as well as moderate expression in plasma membrane and cytoplasm. When treated with concentrations of 5 μM and more of either gefitinib or vandetanib, we observed a significant decrease in cell proliferation. However, there were no detectable changes in p44/42 MAPK and Akt-1 phosphorylation, or in the expression of cyclin D1 or c-Myc following gefitinib or vandetanib treatment. Conclusion We conclude that Ewing sarcoma tumor cell proliferation is not highly sensitive to inhibition of EGFR signaling alone or the simultaneous inhibition of VEGFR receptors, EGFR and RET kinase. Decreased tumor cell proliferation could be achieved with gefitinib and vandetanib, but only at higher doses where non-specific effects of the compounds may be overriding. As Ewing tumor cells do not seem to depend on EGFR and VEGFR pathways for survival, other key factors in the cellular signaling of Ewing sarcoma should be targeted in order to obtain a potent therapeutic response.

  4. Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification.

    Directory of Open Access Journals (Sweden)

    Silvia La Monica

    Full Text Available Despite the initial response, all patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs. The EGFR-T790M secondary mutation is responsible for half of acquired resistance cases, while MET amplification has been associated with acquired resistance in about 5-15% of NSCLCs. Clinical findings indicate the retained addiction of resistant tumors on EGFR signaling. Therefore, we evaluated the molecular mechanisms supporting the therapeutic potential of gefitinib maintenance in the HCC827 GR5 NSCLC cell line harbouring MET amplification as acquired resistance mechanism. We demonstrated that resistant cells can proliferate and survive regardless of the presence of gefitinib, whereas the absence of the drug significantly enhanced cell migration and invasion. Moreover, the continuous exposure to gefitinib prevented the epithelial-mesenchymal transition (EMT with increased E-cadherin expression and down-regulation of vimentin and N-cadherin. Importantly, the inhibition of cellular migration was correlated with the suppression of EGFR-dependent Src, STAT5 and p38 signaling as assessed by a specific kinase array, western blot analysis and silencing functional studies. On the contrary, the lack of effect of gefitinib on EGFR phosphorylation in the H1975 cells (EGFR-T790M correlated with the absence of effects on cell migration and invasion. In conclusion, our findings suggest that certain EGFR-mutated patients may still benefit from a second-line therapy including gefitinib based on the specific mechanism underlying tumor cell resistance.

  5. Multicenter evaluation of rectal cancer reimaging post neoadjuvant (MERRION) therapy.

    LENUS (Irish Health Repository)

    Hanly, Ann M

    2014-04-01

    The aim of this study was to evaluate the utility of reimaging rectal cancer post-CRT (chemoradiotherapy) with magnetic resonance (MR) imaging of the pelvis for local staging and computed tomography of thorax, abdomen, and pelvis (CT TAP) to identify distant metastases.

  6. Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation 
and Apoptosis of Lung Adenocarcinoma Cell H1975

    Directory of Open Access Journals (Sweden)

    Xinyu ZHANG

    2012-03-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC. However, despite an initial response to EGFR-TKIs treatment among responsive patients, most inevitably acquire resistance after a progression-free period of about 10 months. The percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. The aim of this study is to assess the effects of the sequential administration of docetaxel and gefitinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. Methods An MTT assay was used to measure cell proliferation. The potency of the sequential administration of docetaxel and gefitinib were determined by isobolograms and combination index (CI. Cell apoptosis and cycle distribution were determined by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. Results The isobolograms and CI showed that the sequential administration of docetaxel following gefitinib remarkably inhibits cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicate that sequential docetaxel administration following gefitinib blocked the cells in the G2/M phase but not in the G0/G1. The activation of the Caspase-8/Caspase-3 cascade is mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. Conclusion The docetaxel administration following gefitinib might be a new stratagy for lung cancer with T790M mutation after having EGFR-TKIs resistance.

  7. Thyroid cancer post exposure to radiation

    International Nuclear Information System (INIS)

    Reviewed and discussed is the radiation-induced thyroid cancer (TC) from aspects of epidemiology along with the medical and accidental exposure, and of gene level. Medical external exposure to the thyroid occurs by radiation therapy of head and neck diseases and the internal exposure, by radioiodine administration for treatment of Basedow disease and postoperative ablation of TC. Excessive relative risk of TC in A-bomb survivors is 1.15, statistically significant, is 10 times higher in 40 y. TC is generally rare (the incidence, 1 per 100thousands/y), but after the Chernobyl Accident, the incidence is increased to 10-100 times. The incidence of pediatric TC is found to reach the peak at 10 years after the Accident and has decreased to the normal level at present. Instead, TC is now at a peak incidence in adolescents and young adults (15-24 years old) who were exposed at their childhood: risk is found the highest in infants of the age 0-4 y. The exposure was mainly internal by radioiodine through breast milk and food. Histopathological tissue type of TC is rather different from that in Japan, suggesting the low iodine content in the area around Chernobyl. Risk of TC is obscure for the fetal exposure to radioiodine. Chernobyl Tissue Bank has a stock of 3,800 TC specimens. At present, gene mutation specific in radiation-induced TC alone is not found. Although the health risk of exposure to <100 mSv is said to be hardly proven and the internal exposure dose level by the Fukushima Nuclear Power Plant Accident is said to be much lower than that by Chernobyl Accident, the health management of Fukushima residents should be followed up for long term. (T.T.)

  8. Observation of Efficacy and Side Effects of Gefitinib for Advanced Non-small Cell Lung Cancer%吉非替尼治疗晚期非小细胞肺癌的疗效和毒副作用观察

    Institute of Scientific and Technical Information of China (English)

    隋东江; 王蓉美; 李伟生; 赵海霞; 李海燕

    2014-01-01

    目的:观察吉非替尼治疗晚期非小细胞肺癌( NSCLC)的疗效和毒副作用。方法对化疗失败的68例晚期非小细胞肺癌患者进行口服吉非替尼治疗,每日口服250 mg/次,每日1次,1个月之后观察疗效。结果 CR 3例,PR 21例,SD 27例,PD 17例。治疗有效率为35.29%,疾病控制率为75.00%。女性患者的疗效明显优于男性患者,腺癌患者疗效明显优于鳞癌患者的疗效,差异均有统计学意义,P<0.05;疗效与是否采取化疗和有无吸烟史无关(P>0.05);不良反应:皮疹40例,腹泻23例,恶心18例,皮肤干燥11例,经对症处理,均可缓解。结论吉非替尼对晚期非小细胞肺癌疗效较好,其中对于女性以及腺癌的患者治疗效果更好,值得在临床进行深入研究。%Objective To evaluate the efficacy and side effects of gefitinib for advanced non-small cell lung cancer (NSCLC).Methods 68 cases of advanced non-small cell lung cancer patients who failed chemotherapy were treated with ge-fitinib,oral administration of 250 mg/times a day,efficacy was observed after a month .Results CR 3 cases,PR 21 cases,SD 27 cases,PD 17 cases.The effective rate was 35.29%,disease control rate was 75.00%.Efficacy of female patients was significantly better than that of male patients ,the efficacy of cancer patients were significantly better than patients with squamous cell carcino -ma,the differences were statistically significant ,P0.05);adverse reactions:skin rash in 40 cases,23 cases of diarrhea,nausea in 18 cases,11 cases of dry skin,they can be allevia-ted with symptomatic treatment .Conclusion Gefitinib for advanced non-small cell lung cancer is effective , and it has better effect for women and adenocarcinoma ,it is worthy of further study in clinical practice .

  9. Young women's construction of their post-cancer fertility.

    Science.gov (United States)

    Dryden, Amy; Ussher, Jane M; Perz, Janette

    2014-01-01

    Younger women diagnosed with cancer often face compromised fertility as a result of their treatment. However, previous research has adopted a biomedical model of fertility and utilised hypothetico-deductive research methods which have not allowed for full exploration of women's subjectivity. This study explored younger women's construction of their fertility post-cancer, and their discussions of fertility with healthcare professionals, from a social constructionist epistemology. Semi-structured one-to-one interviews were conducted with eight women aged 18-26, across a variety of cancer types. Foucaultian Discourse Analysis identified three subject positions associated with fertility concerns: 'Inadequate woman: Accepting the motherhood mandate'; 'Adequate woman: Resisting the motherhood mandate'; and 'Survival of the fittest: Woman as genetically defective'. Implications of these subject positions included feelings of inadequacy, fear and devastation; feeling undesirable to romantic partners; and concern about passing on cancer-positive genes. In describing healthcare professional interactions, women adopted positions of 'Satisfied patient'; 'Passive recipient patient'; or 'Resisting the passive patient position'. Accounts of inadequate information provision were associated with anger and frustration, whereas feeling adequately informed was associated with satisfaction at making decisions about fertility preservation. These results suggest that fertility is of importance to young women cancer survivors, and that compromised fertility can negatively impact subjectivity. PMID:24916140

  10. Cancer-Related Post-traumatic Stress (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about post-traumatic stress and related symptoms in cancer patients, cancer survivors, and their family members. Assessment and treatment of these symptoms are discussed.

  11. Cancer-Related Post-traumatic Stress (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about post-traumatic stress and related symptoms in cancer patients, cancer survivors, and their family members. Assessment and treatment of these symptoms are discussed.

  12. Esophageal Cancer: Role of Imaging in Primary Staging and Response Assessment Post Neoadjuvant Therapy.

    Science.gov (United States)

    Griffin, Yvette

    2016-08-01

    Advances in the early detection and treatment of esophageal cancer have meant improved survival rates for patients with esophageal cancer. Accurate pretreatment and post-neoadjuvant treatment staging of esophageal cancer is essential for assessing operability and determining the optimum treatment plan. This article reviews the multimodality imaging approach in the diagnosis, staging, and assessment of treatment response in esophageal cancer. PMID:27342898

  13. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib

    DEFF Research Database (Denmark)

    Hare, Kristine Juul; Hartmann, Bolette; Kissow, Hannelouise; Holst, Jens Juul; Poulsen, Steen Seier

    2007-01-01

    PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been introduced as antitumor agents in the treatment of cancers overexpressing the receptor. The treatment has gastrointestinal side effects which may decrease patient compliance and limit the efficacy. Glucagon...... examine whether the inhibition of the EGFR induces intestinal atrophy and if this can be counteracted by treatment with GLP-2. EXPERIMENTAL DESIGN: Mice were treated for 10 days with either gefitinib orally, GLP-2 as injections, or a combination of both. After sacrifice, the weight and length of the...

  14. Predictors of re-operation due to post-surgical bleeding in breast cancer patients

    DEFF Research Database (Denmark)

    Winther Lietzen, L; Cronin-Fenton, Deirdre; Garne, Jens Peter;

    2012-01-01

    To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation.......To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation....

  15. Evaluating biomarkers to model cancer risk post cosmic ray exposure

    Science.gov (United States)

    Sridharan, Deepa M.; Asaithamby, Aroumougame; Blattnig, Steve R.; Costes, Sylvain V.; Doetsch, Paul W.; Dynan, William S.; Hahnfeldt, Philip; Hlatky, Lynn; Kidane, Yared; Kronenberg, Amy; Naidu, Mamta D.; Peterson, Leif E.; Plante, Ianik; Ponomarev, Artem L.; Saha, Janapriya; Snijders, Antoine M.; Srinivasan, Kalayarasan; Tang, Jonathan; Werner, Erica; Pluth, Janice M.

    2016-06-01

    Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing

  16. Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR

    Science.gov (United States)

    Yang, Hua; Wang, Rong; Peng, Shunli; Chen, Longhua; Li, Qi; Wang, Wei

    2016-01-01

    Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is an option for lung cancers harboring wild-type EGFR when chemotherapeutic reagents have failed. In this study, we found that the EGFR-TKI, gefitinib, modestly suppressed proliferation of the lung cancer cell lines, A549 and H358, which both harbor wild-type EGFR. Treatment with hepatocyte growth factor (HGF) reduced the sensitivity to gefitinib, whereas sensitivity was restored by treatment with an HGF antibody, a MET inhibitor, or depletion of MET but not ErbB3 gene. Moreover, both PI3K/mTOR inhibitors and MEK inhibitors suppressed proliferation of A549 cells, whereas only PI3K/mTOR inhibitors effectively suppressed cell viability of EGFR mutant PC-9 cells. Our findings suggest that HGF reduced the gefitinib sensitivity through MET and downstream PI3K and MAPK pathways. Combined use of EGFR-TKI and MET inhibitors or inhibition of downstream signaling molecules might be a better second or third line choice for a group of patients with advanced lung cancer harboring wild-type EGFR. PMID:26919104

  17. Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Yutao LIU

    2014-05-01

    Full Text Available Background and objective Lung cancer in young patients (less or equal to 45 years is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017. The median overall survival (OS was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028 and receiving other anti-cancer treatment after Gefitinib therapy (P<0.001. Conclusion The median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were similar with general population.

  18. Post-operative complications of gastric cancer surgery: female gender at high risk

    OpenAIRE

    Sah, BK; ZHU, ZG; Wang, XY; YANG, QM; CHEN, MM; Xiang, M.; Chen, J.; Yan, M

    2009-01-01

    We applied physiological and operative severity score for the enumeration of morbidity and mortality (POSSUM) to evaluate overall surgical outcome and investigated the role of gender for early post-operative complications in gastric cancer surgery. The data from a total of 357 patients of gastric cancer were analysed by univariate and multivariate analysis. Post-operative complications were recorded according to definition of POSSUM. Post-operative complications of male and female patients we...

  19. Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells

    International Nuclear Information System (INIS)

    Aberrant ErbB receptor signaling is associated with various types of malignancies. γ-Tocotrienol is a member of the vitamin E family of compounds that displays potent anticancer activity that is associated with suppression in ErbB receptor phosphorylation and mitogenic signaling. Erlotinib and gefitinib are tyrosine kinase inhibitors that block ErbB1 receptor activation, whereas trastuzumab is a monoclonal antibody that has been designed to specifically inhibit ErbB2 receptor activation. However, the clinical effectiveness of these agents have been disappointing because of cooperation between different ErbB family members that can rescue cancer cells from agents directed against a single ErbB receptor subtype. It was hypothesized that targeting multiple ErbB receptor subtypes with combined treatment of γ-tocotrienol and ErbB receptor inhibitors would provide greater anticancer effects than monotherapy targeting only a single ErbB receptor subtype. Highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined media containing 10 ng/ml EGF as a mitogen. Cell viability wase determined by MTT assay, whereas Western blot and immunofluorescent staining was used to determine treatment effects on ErbB receptor subtype level and activation. Treatment-induced apoptosis was determined using annexin V staining and Western blot analysis of cleaved caspase-3 and PARP levels. Treatment with 3.5 μM γ-tocotrienol, 0.5 μM erlotinib or 1.0 μM gefitinib alone, significantly inhibited +SA tumor cell growth. Combined treatment with subeffective doses of erlotinib (0.25 μM) or gefitinib (0.5 μM) with subeffective doses of γ-tocotrienol (0.5-3.0 μM) significantly inhibited the growth and induced apoptosis in a dose-responsive manner. Trastuzumab treatment alone or in combination had no effect on +SA cell growth and viability. Combined treatment of γ-tocotrienol with erlotinib or gefitinib also cause a large decrease in ErbB3, ErbB4, and to

  20. SB365, Pulsatilla saponin D, suppresses the growth of gefitinib-resistant NSCLC cells with Met amplification.

    Science.gov (United States)

    Jang, Won-Jun; Park, Byoungduck; Jeong, Gil-Saeng; Hong, Soon-Sun; Jeong, Chul-Ho

    2014-12-01

    Clinical treatment using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib has been applied in patients with non-small cell lung cancers (NSCLCs). Unfortunately, acquired drug resistance emerges in these patients due to the amplification of the Met proto-oncogene, which may be a compensatory mechanism of NSCLCs against EGFR inhibition. To overcome this resistance, identification of new small-molecule natural compounds is crucial for cancer therapeutics. In this regard, SB365, saponin D from the root of Pulsatilla koreana which has been used as a traditional medicine in Korea for several diseases, has attracted wide interest. In the present study, SB365 effectively suppressed the proliferation of gefitinib-resistant HCC827GR NSCLC cells with Met amplification. Notably, our data revealed that SB365 inhibited the phosphorylation of Met and the downstream signaling pathway required for growth and survival in the Met-amplified HCC827GR cells. Moreover, SB365 suppressed the anchorage-independent growth, migration and invasion along with induction of apoptosis in the HCC827GR cells. Therefore, these results suggest that SB365 is good candidate as a natural product for use in the treatment of Met-amplified NSCLCs. PMID:25310337

  1. Gene signature of the post-Chernobyl papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Handkiewicz-Junak, Daria; Rusinek, Dagmara; Oczko-Wojciechowska, Malgorzata; Kowalska, Malgorzata; Jarzab, Barbara [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Department of Nuclear Medicine and Endocrine Oncology, Gliwice (Poland); Swierniak, Michal [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Department of Nuclear Medicine and Endocrine Oncology, Gliwice (Poland); Medical University of Warsaw, Genomic Medicine, Department of General, Transplant and Liver Surgery, Warsaw (Poland); Dom, Genevieve; Maenhaut, Carine; Detours, Vincent [Universite libre de Bruxelles (ULB), Institute of Interdisciplinary Research, Bruxelles (Belgium); Unger, Kristian [Imperial College London Hammersmith Hospital, Human Cancer Studies Group, Division of Surgery and Cancer, London (United Kingdom); Helmholtz-Zentrum, Research Unit Radiation Cytogenetics, Munich (Germany); Bogdanova, Tetiana [Institute of Endocrinology and Metabolism, Kiev (Ukraine); Thomas, Geraldine [Imperial College London Hammersmith Hospital, Human Cancer Studies Group, Division of Surgery and Cancer, London (United Kingdom); Likhtarov, Ilya [Academy of Technological Sciences of Ukraine, Radiation Protection Institute, Kiev (Ukraine); Jaksik, Roman [Silesian University of Technology, Systems Engineering Group, Faculty of Automatic Control, Electronics and Informatics, Gliwice (Poland); Chmielik, Ewa [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Department of Tumour Pathology, Gliwice (Poland); Jarzab, Michal [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, IIIrd Department of Radiation Therapy, Gliwice (Poland); Swierniak, Andrzej [Silesian University of Technology, Department of Automatic Control, Gliwice (Poland)

    2016-07-15

    Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure. (orig.)

  2. Gene signature of the post-Chernobyl papillary thyroid cancer

    International Nuclear Information System (INIS)

    Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure. (orig.)

  3. Analysis of the relationship between lung cancer drug response level and atom connectivity dynamics based on trimmed Delaunay triangulation

    Science.gov (United States)

    Zou, Bin; Wang, Debby D.; Ma, Lichun; Chen, Lijiang; Yan, Hong

    2016-05-01

    Epidermal growth factor receptor (EGFR) mutation is a pathogenic factor of non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs), such as gefitinib, are widely used in NSCLC treatment. In this work, we investigated the relationship between the number of EGFR residues connected with gefitinib and the response level for each EGFR mutation type. Three-dimensional trimmed Delaunay triangulation was applied to construct connections between EGFR residues and gefitinib atoms. Through molecular dynamics (MD) simulations, we discovered that when the number of EGFR residues connected with gefitinib increases, the response level of the corresponding EGFR mutation tends to descend.

  4. Hyoid Displacement in Post-Treatment Cancer Patients: Preliminary Findings

    Science.gov (United States)

    Zu, Yihe; Yang, Zhenyu; Perlman, Adrienne L.

    2011-01-01

    Purpose: Dysphagia after head and neck cancer treatment is a health care issue; in some cases, the cause of death is not cancer but, rather, the passage of food or liquid into the lungs. Hyoid displacement is known to be important to safe swallowing function. The purpose of this study was to evaluate hyoid displacement after cancer treatment.…

  5. Randomized double-blind trial of prophylactic topical Evozac® Calming Skin Spray for gefitinib-associated acne-like eruption

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-07-01

    Full Text Available Yalan Wang,* Yunpeng Yang,* Jinxia Xu, Juan Yu, Xia Liu, Ruizhen Gao, Li Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China *These authors contributed equally to this work Background: "Gefitinib" is a first-generation epidermal growth factor receptor tyrosine-kinase inhibitor. More than half of patients receiving gefitinib develop acne-like eruption. Evozac® Calming Skin Spray (Evaux Laboratoires, Évaux-les-Bains, France is made of Évaux thermal spring water and commonly used for the treatment of dermatological toxicities caused by anti- epidermal growth factor receptor therapy. The aim of the study reported here was to test the effect of Evozac Calming Skin Spray on the prevention of rash in patients receiving gefitinib. Methods: Non-small-cell lung cancer patients preparing to initiate gefitinib therapy were randomly assigned to apply Evozac Calming Skin Spray or physiological saline to the face three times a day. The treatment was started on the same day as initiation of gefitinib therapy and continued for 4 weeks. Results: A total of 51 patients in the Evozac Calming Skin Spray group and 50 patients in the physiological saline group completed the study per the protocol. The number of facial lesions peaked at the end of 3 weeks in both groups. There were significantly fewer lesions in the Evozac Calming Skin Spray group than in the physiological saline group at the end of 1 week (0.25 versus [vs] 1.10, P=0.031 and 3 weeks (6.67 vs 12.26, P=0.022. Patients from the Evozac Calming Skin Spray group also developed fewer facial lesions at the end of 2 weeks and 4 weeks, however, the difference was not statistically significant. At the end of 4 weeks, fewer patients from the Evozac Calming Skin Spray group developed rash of grade 2 or greater severity (17.6% vs 36.0%, P=0.037, or experienced rash

  6. NVP-BEZ235 overcomes gefitinib-acquired resistance by down-regulating PI3K/AKT/ mTOR phosphorylation

    Directory of Open Access Journals (Sweden)

    Sun ZH

    2015-01-01

    Full Text Available Zhihua Sun,2,* Qiuhui li,1,* Sheng Zhang,1 Jing Chen,1 Lili Huang,3 Jinghua Ren,1 Yu Chang,1 Yichen Liang,1 Gang Wu1 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Oncology department, Xiangyang central Hospital, Xiangyang, Hubei, People’s Republic of China; 3Radiation Oncology Department, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China *These authors contributed equally to this work Background: Patients harboring activating mutations in epidermal growth factor receptors (EGFR are particularly sensitive to EGFR tyrosine kinase inhibitors (TKIs. However, most patients develop an acquired resistance after a period of about 10 months. This study focuses on the therapeutic effect of NVP-BEZ235, a dual inhibitor of phosphatidylinositol- 3-kinase/mammalian target of rapamycin (PI3K/mTOR, in gefitinib-resistant non-small cell lung cancer. Methods: H1975 cell line was validated as a gefitinib-resistant cell model by the nucleotide-sequence analysis. We used the 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay to detect the growth of H1975 cell line in vitro. H1975 cells' migration was detected by the migration assay. Xenograft models were used to investigate the growth of gefitinib-resistant non-small cell lung cancer in vivo. Western blot and immunohistochemical analysis were used to investigate the level of PI3K/protein kinase B(AKT/mTOR signaling pathway proteins. Results: We show that NVP-BEZ235 effectively inhibited the growth of H1975 cells in vivo as well as in vitro. Similarly, H1975 cell migration was reduced by NVP-BEZ235. Further experiments revealed that NVP-BEZ235 attenuated the phosphorylation of PI3K/AKT/mTOR signaling pathway proteins. Conclusion: Taken together, we suggest that NVP-BEZ235 inhibits gefitinib-resistant tumor growth by downregulating PI3K

  7. The CANSURVIVOR Project : meeting post-treatment cancer survivors’ needs

    OpenAIRE

    Ivers, Mary E.; Dooley, Barbara A.; Bates, Ursula

    2009-01-01

    Cancer survivor numbers in Ireland are increasing due to the success of modern treatments. Although most survivors have a good quality of life not all survivors return to 'normal' after treatment. The HSE funded CANSURVIVOR research project has found that many survivors have difficulties and need help to recover and adjust after cancer treatment. Over a number of exploratory studies using interviews, focus groups and a survey of 262 breast, prostate, colorectal and lung cancer survivors, the ...

  8. Complexities of Adherence and Post-Cancer Lymphedema Management

    OpenAIRE

    Ostby, Pamela L.; Jane M Armer

    2015-01-01

    Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL), a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing ...

  9. Mucin-producins Lung Cancer and Response to Gefitinib.

    OpenAIRE

    Yasushi,Akiyama; Junko,Kato; Kenichiro,Itoh; Chihnatsu,Moriyama; Michihiro,Fujino; Masashi,Ohe; Fujiya,Kishi

    2006-01-01

    A53-year-01d woman who was hypoxemic due to primary lung adenocarcinoma with both pleuritis and pericarditis carcinomatosa was treated with gefitinib,an inhibitor of the epithelial growth factor receptor (EGFR) tyrosine kinase.The tumor seemed to produce mucin because the extremely high serum KL-6 and almost normal Sp-D values on admission.After 3 days of treatment,the patient became asymptomatic and oxygen was discontinued.The response to this drug was remarkable on chest CT findings.Mucin o...

  10. The post hoc use of randomised controlled trials to explore drug associated cancer outcomes

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; Zoungas, Sophia; Chalmers, John;

    2013-01-01

    on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of Randomised controlled trials (RCTs) designed for other purposes. METHODOLOGICAL CHALLENGES TO CONSIDER: We set out to perform a post......INTRODUCTION: Drug-induced cancer risk is of increasing interest. Both observational studies and data from clinical trials have linked several widely used treatments to cancer. When a signal for a potential drug-cancer association is generated, substantiation is required to assess the impact...... challenges must be addressed to enhance the likelihood of reliable conclusions. Advantages of post-hoc analyses of RCTs include quality of data collected and sometimes randomisation to exposure of interest. Limitations include confounding and sample size, which is fixed to suit the purposes of the trial...

  11. Perspectives of the Breast Cancer Survivorship Continuum: Diagnosis through 30 Months Post-Treatment

    Directory of Open Access Journals (Sweden)

    Jennifer M. Hulett

    2015-05-01

    Full Text Available This study explored breast cancer survivors’ perspectives regarding their experiences of the survivorship continuum from diagnosis through 30 months post-treatment. The sample included women (N = 379 with newly-diagnosed breast cancer undergoing treatment at a Midwestern university-affiliated cancer center. Semi-structured interviews were conducted using the Lymphedema and Breast Cancer Questionnaire at time of diagnosis, post-operatively, quarterly during the first year, and then semi-annually thereafter through 30 months post-treatment. A mixed-methodology was used to analyze participants’ comments. Themes central to long-term survivorship experiences included social support, positive worldviews, breast cancer and lymphedema health literacy, religious/spiritual beliefs, self-empowerment, and recovery expectations. These themes were consistent with a psychoneuroimmunological model of health in which psychosocial variables mediate stress and influence health outcomes. Qualitative data showed that social support and positive worldviews were the two themes with the most significant impact on long-term breast cancer survivorship experiences. Survivors expressed a need to advance their health care literacy in order to share ownership of breast cancer and lymphedema treatment decisions. Since breast cancer is an immune-mediated disease, long-term survivorship planning should address psychosocial factors that influence the long-term psychological distress associated with immune dysfunction.

  12. Identification of Degradant Impurity in Gefitinib by Using Validated RRLC Method

    OpenAIRE

    Madireddy Venkataramanna; Indukuri Venkata Somaraju; Kondra Sudhakar Babu

    2011-01-01

    Degradation pathway for gefitinib is established as per ICH recommendations by validated and stability in-dicating reverse phase liquid chromatographic method. Gefitinib is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress condi-tions. Two impurities are studied among which one impurity is found prominent degradant. The stress sam-ples are assayed against a qualified reference standard and the mass bala...

  13. Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

    Energy Technology Data Exchange (ETDEWEB)

    Scholten, Ernst T. [University Medical Centre, Department of Radiology, Utrecht (Netherlands); Kennemer Gasthuis, Department of Radiology, Haarlem (Netherlands); Horeweg, Nanda [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Erasmus University Medical Centre, Department of Pulmonary Medicine, Rotterdam (Netherlands); Koning, Harry J. de [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Centre Groningen, Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Mali, Willem P.T.M.; Jong, Pim A. de [University Medical Centre, Department of Radiology, Utrecht (Netherlands)

    2015-01-15

    To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

  14. Post Diagnosis Diet Quality and Colorectal Cancer Survival in Women

    OpenAIRE

    Fung, Teresa T.; Kashambwa, Rutendo; Sato, Kaori; Chiuve, Stephanie E.; Fuchs, Charles S.; Wu, Kana; Giovannucci, Edward; Ogino, Shuji; Hu, Frank B.; Meyerhardt, Jeffrey A.

    2014-01-01

    Background: Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival. Methods: 1201 women diagnosed with stage I–III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alt...

  15. Global histone post-translational modifications and cancer:Biomarkers for diagnosis,prognosis and treatment?

    Institute of Scientific and Technical Information of China (English)

    Shafqat; Ali; Khan; Divya; Reddy; Sanjay; Gupta

    2015-01-01

    Global alterations in epigenetic landscape are now recognized as a hallmark of cancer. Epigenetic mechanismssuch as DNA methylation,histone modifications,nucleosome positioning and non-coding RNAs are proven to have strong association with cancer. In particular,covalent post-translational modifications of histone proteins are known to play an important role in chromatin remodeling and thereby in regulation of gene expression. Further,histone modifications have also been associated with different aspects of carcinogenesis and have been studied for their role in the better management of cancer patients. In this review,we will explore and discuss how histone modifications are involved in cancer diagnosis,prognosis and treatment.

  16. Post-sampling mortality and non-response patterns in the English Cancer Patient Experience Survey: Implications for epidemiological studies based on surveys of cancer patients

    OpenAIRE

    Abel, Gary A; Saunders, Catherine L; Lyratzopoulos, Georgios

    2015-01-01

    BACKGROUND: Surveys of the experience of cancer patients are increasingly being introduced in different countries and used in cancer epidemiology research. We examine how sampling processes, post-sampling mortality and survey non-response influence the representativeness of cancer patient surveys. METHODS: We examined predictors of post-sampling mortality and non-response among patients initially included in the sampling frame of the English Cancer Patient Experience Survey. We also comp...

  17. Post-discharge symptoms following fast-track colonic cancer surgery: a phenomenological hermeneutic study

    DEFF Research Database (Denmark)

    Krogsgaard, Marianne; Dreyer, Pia; Egerod, Ingrid; Jarden, Mary

    2014-01-01

    OBJECTIVE: To obtain knowledge of patients' experiences of postoperative symptoms during the initial two weeks following fast-track colonic cancer surgery. METHOD: Semi-structured in-depth interviews with seven colonic cancer patients two weeks post hospital discharge. Analysis was performed using...... programmes lead to shorter hospitalisation and improved physical performance, post-colonic surgery patients experience various symptoms after discharge. Healthcare professionals need to address symptoms that might have immediate and long-term consequences on patients' everyday life. Follow-up studies are...

  18. Post-traumatic growth among elderly women with breast cancer compared to breast cancer-free women

    DEFF Research Database (Denmark)

    Brix, Sofie Andersen; Bidstrup, Pernille Envold; Christensen, Jane;

    2013-01-01

    Although breast cancer (BC) may have negative psychological sequelae, it may also be experienced as an existential challenge, which can derive personal growth. Only one study has been conducted, however, on whether women with BC experience more post-traumatic growth (PTG) than BC-free women. We...

  19. Cancer genetic counseling: communication and counselees' post-visit satisfaction, cognitions, anxiety and needs fulfillment.

    OpenAIRE

    Pieterse, A H; van Dulmen, A M; Beemer, F A; Bensing, J M; Ausems, M.G.E.M.

    2007-01-01

    Little is known about the relation between communication during cancer genetic counseling and outcome. We assessed associations between counselor-counselee communication and counselee satisfaction, cognitions, anxiety, and fulfillment of major needs, corrected for pre-visit levels as appropriate. In total 171 consecutive new counselees, mainly referred for breast or colon cancer, received pre- and post-visit questionnaires assessing needs/fulfillment, knowledge, perceived control (PPC), anxie...

  20. Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients undergoing lung resection

    OpenAIRE

    YANO, MOTOKI; Sasaki, Hidefumi; MORIYAMA, SATORU; HIKOSAKA, YU; YOKOTA, KEISUKE; Kobayashi, Susumu; HARA, MASAKI; Fujii, Yoshitaka

    2011-01-01

    Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer patients is a critical factor in post-operative mortality. The cause of AE development is unknown and AE may occur in patients without the diagnosis of IPF. We have conducted a retrospective study of consecutive patients who underwent lung cancer surgery since January 2004. Sixty-two patients with fibrous findings in preoperative high-resolution computed tomography were enrolled in the present study and clinicopatho...

  1. Enhancing Supportive-Educative Nursing Systems to Reduce Risk of Post-Breast Cancer Lymphedema

    OpenAIRE

    Jane M Armer; Shook, Robin P.; Schneider, Melanie K; Brooks, Constance W.; Peterson, Julie; Stewart, Bob R.

    2009-01-01

    This study describes the use of data regarding self-care agency to enhance a supportive-educative nursing system for breast cancer survivors to reduce the risk of developing lymphedema post surgery. Impetus for this study came from the analysis of participant feedback from a parent study (Lance Armstrong Foundation pilot study) that sought to plan an educational program for nurses that will improve their supportive-educative nursing system when working with breast cancer survivors. The goal i...

  2. Pyometra presenting in conjunction with bowel cancer in a post-menopausal women: a case report

    OpenAIRE

    Soleymani majd, Hooman; Watermeyer, Sean; Ismail, Lamiese

    2008-01-01

    This case describes a 71 year old, post-menopausal woman who developed vaginal discharge. This complaint ultimately led to the discovery of bowel cancer in conjunction with a large sterile pyometra. The pyometra was not due to genital malignancy. The most likely conclusion is that the pyometra may have arisen as an inflammatory response to the adjacent bowel pathology. This case report highlights the need for clinicians to consider non-gynaecological cancer as a possible cause for otherwise u...

  3. Post-chemotherapy arthralgia and arthritis in lung cancer

    Directory of Open Access Journals (Sweden)

    Aref H Amiri

    2012-01-01

    Full Text Available Objective: Evaluate the characteristics of arthritis, arthralgia and musculoskeletal pain after chemotherapy in patients with lung cancer. Materials and Methods: In this study, we evaluate the characteristics of 17 patients with joint symptoms following receiving chemotherapy for lung cancer. Demographic information of patients including sex, age, time of rheumatologic findings after starting of chemotherapy, time of improvement after starting of medication, and relevant laboratory findings for each patient. Results: A total of seventeen patients (six women with mean age 41.2 ± 5.2 years and 11 men with mean age 42.5 ± 8.2 that received standard chemotherapy for lung cancer according to stage of disease. Joint symptoms usually began about seven months after the first session of chemotherapy. Patients had an average of two tender joints and 1 hr of morning stiffness. Four patients were positive for anti-nuclear antibody, and none of patient was positive for rheumatoid factor. Non-steroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DMARD, corticosteroids, and venlafaxine were prescribed. Four patients did not show an improvement. Follow-up was available for all patients. 11 patients showed favorable responses, characterized by a significant decrease (more than 50% in morning stiffness, pain, and tender joint counts after a mean of three months′ treatment. Two patients had complete resolution of symptoms and did not required further medications for arthritis, arthralgia or musculoskeletal pain. Conclusion: Chemotherapy-related arthropathy in lung cancer is not uncommon. Early treatment with NSAID, DMARD, and corticosteroids is effective in the majority of patients.

  4. Post-traumatic stress symptoms and post-traumatic growth in 223 childhood cancer survivors: predictive risk factors

    Directory of Open Access Journals (Sweden)

    Marta eTremolada

    2016-02-01

    Full Text Available With modern therapies and supportive care, survival rates of childhood cancer have increased considerably. However, there are long-term psychological sequelae of these treatments that may not manifest until pediatric survivors are into adulthood. The prevalence of post-traumatic stress disorder (PTSD in young adult survivors of childhood cancer ranges from 6.2% to 22%; associated risk factors are young age at the assessment, female gender, low education level and some disease-related factors. The aim of this study was to investigate, in adolescent and young adult (AYA survivors of childhood cancer, the incidence and severity of post-traumatic stress symptoms (PTSS, and to identify the risk factors and the associated post-traumatic growth (PTG index.Participants were 223 AYA cancer survivors recruited during follow-up visits in the Oncohematology Clinic of the Department of Child and Woman’s Health, University of Padua. Data were collected from self-report questionnaires on PTSS incidence, PTG mean score, perceived social support, and medical and socio-demographic factors. Ex-patients’ mean age at the assessment was 19.33 years (SD = 3.01, 15-25, 123 males and 100 females, with a mean of years off-therapy of 9.64 (SD=4.17. Most (52.5% had survived an hematological disorder and 47.5% a solid tumor when they were aged, on average, 8.02 years (SD=4.40.The main results indicated a moderate presence of clinical (≥9 symptoms: 9.4% and sub-clinical PTSS (6-8 symptoms: 11.2%, with the avoidance criterion most often encountered. Re-experience symptoms and PTG mean score were significantly associated (r=0.24 p=0.0001. A hierarchical regression model (R2 = 0.08; F = 1.46; p = 0.05 identified female gender (β = 0.16; p = 0.05 and less perceived social support (β = -0.43; p = 0.05 as risk factors to developing PTSS. Another hierarchical regression model assessed the possible predictors of the PTG total score (R2 = 0.36; F = 9.1; p = 0.0001, with

  5. Recovery at the post anaesthetic care unit after breast cancer surgery

    DEFF Research Database (Denmark)

    Gärtner, Rune; Callesen, Torben; Kroman, Niels Thorndahl;

    2010-01-01

    Extant literature shows that women having undergone breast cancer surgery have substantial problems at the post-anaesthesia care unit (PACU). Based on nursing reports and elements of the discharge scoring system recommended by The Danish Society of Anaesthesiology and Intensive Care Medicine, the...

  6. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Helmerhorst, Theo; Habbema, Dik;

    2012-01-01

    To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result....

  7. Recovery at the post anaesthetic care unit after breast cancer surgery

    DEFF Research Database (Denmark)

    Gärtner, Rune; Callesen, Torben; Kroman, Niels Thorndahl; Kehlet, Henrik

    2010-01-01

    Extant literature shows that women having undergone breast cancer surgery have substantial problems at the post-anaesthesia care unit (PACU). Based on nursing reports and elements of the discharge scoring system recommended by The Danish Society of Anaesthesiology and Intensive Care Medicine, the...... present prospective, observational study aims to determine why these patients stayed at PACU....

  8. Complexities of Adherence and Post-Cancer Lymphedema Management

    Directory of Open Access Journals (Sweden)

    Pamela L. Ostby

    2015-11-01

    Full Text Available Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL, a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005–2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eight studies included outcome measures of adherence to BCRL treatment regimens with a subsequent improvement in reduced limb volumes and/or perceptions of self-efficacy and self-regulation. A major limitation is the few number of rigorously developed outcome measures of BCRL adherence. In addition, randomized studies are needed with larger sample sizes to establish adequate levels of evidence for establishing best practice standards for improving adherence to BCRL self-management treatment regimens.

  9. Complexities of Adherence and Post-Cancer Lymphedema Management.

    Science.gov (United States)

    Ostby, Pamela L; Armer, Jane M

    2015-01-01

    Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL), a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005-2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eight studies included outcome measures of adherence to BCRL treatment regimens with a subsequent improvement in reduced limb volumes and/or perceptions of self-efficacy and self-regulation. A major limitation is the few number of rigorously developed outcome measures of BCRL adherence. In addition, randomized studies are needed with larger sample sizes to establish adequate levels of evidence for establishing best practice standards for improving adherence to BCRL self-management treatment regimens. PMID:26580657

  10. A comparative study of pre- and post-menopausal breast cancer: Risk factors, presentation, characteristics and management

    OpenAIRE

    Surakasula, Aruna; Nagarjunapu, Govardhana Chary; Raghavaiah, K. V.

    2014-01-01

    Objective: Breast cancer is the most common female cancer worldwide and is the second most commonly diagnosed cancer in Indian women. This study evaluates the differences between pre- and post-menopausal breast cancer women regarding risk factors, nature of disease presentation, tumor characteristics, and management. Methods: This is a prospective observational study, conducted in the Oncology Department of St. Ann's Cancer Hospital, for a period of 6 months from January to August 2012. Data ...

  11. Treatment of cultured glioma cells with the EGFR-TKI gefitinib (''Iressa'', ZD1839) increases the uptake of astatinated EGF despite the absence of gefitinib-mediated growth inhibition

    International Nuclear Information System (INIS)

    The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib (''Iressa'', ZD1839), a reversible growth inhibitor of EGFR-expressing tumour cells, has been shown to enhance the antitumour effect of ionising radiation, and also to increase the uptake of radioiodinated EGF. Thus, combination of gefitinib treatment and radionuclide targeting is an interesting option for therapy of brain tumours that are difficult to treat with conventional methods. The aim of this study was to evaluate how pre-treatment with gefitinib affects binding of astatinated EGF (211At-EGF) to cultured glioma U343 cells, which express high levels of EGFR. The growth of U343 cells in the presence of gefitinib was investigated, and it was found that gefitinib does not significantly inhibit the growth of these cells. Nevertheless, the uptake of 211At-EGF in U343 cells was markedly increased (up to 3.5 times) in cells pre-treated with gefitinib (1 μM). This indicates that a combination of gefitinib treatment and radionuclide targeting to EGFR might be a useful therapeutic modality, even for patients who do not respond to treatment with gefitinib alone. (orig.)

  12. Post diagnosis diet quality and colorectal cancer survival in women.

    Directory of Open Access Journals (Sweden)

    Teresa T Fung

    Full Text Available Dietary factors are known to influence colorectal cancer (CRC risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC survival.1201 women diagnosed with stage I-III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010, alternate Mediterranean Diet score (aMED and Dietary Approaches to Stop Hypertension score (DASH and derived two dietary patterns, Western (unhealthy and prudent (healthy, by principal component analysis for each woman.During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles = 0.71, 95% CI 0.52-0.98, p trend = 0.01 as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1 = 0.72, 95% CI = 0.43-1.21, p trend = 0.07. When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5-15 g/d = 1.30, 95%CI = 1.05-1.61 and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving = 1.11, 95% CI = 1.01-1.23. No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality.Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations.

  13. The pathology of thyroid cancer in Ukraine post Chernobyl

    International Nuclear Information System (INIS)

    We have analyzed data on the sex and age distribution of 122 cases which have been operated at the Institute of Endocrinology and Metabolism in Kiev, Ukraine during the period January 1990 to December 1994 and compared these to information on 154 cases recorded by the UK Childhood Cancer Registry in England and Wales over the period 1963-1992. The histology has also been reviewed in 114 cases from Ukraine and in 81 cases in England and Wales. In addition immunocytochemistry for calcitonin, thyroglobulin, ret, met, IGF1 receptor and p53 and in situ hybridisation for thyroglobulin, calcitonin, and IGF1 mRNAs has been performed on a sample of cases from each of the two series. Our results show that there are clear differences between the sex and age distributions of the two series. In England and Wales there is a smooth rise with increasing age, but in Ukraine there was a peak incidence at eight years of age. The sex distribution was closer to equivalence in Ukraine then in England and Wales. The majority of thyroid carcinomas were papillary in type in both series, but Ukraine showed a higher frequency (96% compared with 68%). In addition, there was a particularly high incidence of the solid/follicular subtype of papillary carcinoma in children from Ukraine. There is a clear change in the age threshold for development of thyroid carcinoma over time, consistent with a causative agent at the time of the Chernobyl accident, and suggesting that the causative agent does not persist in the environment. These findings provide strong evidence for exposure to radioisotopes of iodine as the cause of the considerable increase in the incidence of childhood thyroid cancer in the Ukraine

  14. A Longitudinal Study of Post-Traumatic Growth and Psychological Distress in Colorectal Cancer Survivors.

    Science.gov (United States)

    Occhipinti, Stefano; Chambers, Suzanne K; Lepore, Stephen; Aitken, Joanne; Dunn, Jeff

    2015-01-01

    The stability of post-traumatic growth over time and the relationship between post-traumatic growth and traditional distress outcomes remains unclear. We tracked post-traumatic growth in a population-based sample of colorectal cancer patients from soon after diagnosis to five years subsequently to assess the heterogeneity of a post-traumatic growth response to cancer over time and describe the simultaneous and longitudinal relationships between post-traumatic growth and psychological distress. 1966 colorectal patients who were five months post diagnosis were assessed six times over a five year period. There was considerable heterogeneity associated with both psychological distress and benefit finding scores over time. However, both for benefit finding and psychological distress, the variation in individual scores suggested an underlying positive linear trend and both lagged and lagged change components. Specifically, benefit finding and psychological distress are mutual leading indicators of each other. First, benefit finding served as a leading indicator of distress, in that increases in reported benefit finding from year to year predicted higher future increases in psychological distress. As well, in an inverse relationship, psychological distress served as a leading indicator of benefit finding, such that increases in reported distress from year to year predicted lower future increases in benefit finding. Post-traumatic growth may reflect patients coping efforts to enhance perceptions of wellbeing in response to escalating cancer-related threats, acting as harbinger of increasing trajectories of psychological distress. This explanation is consistent with a cognitive dissonance response in which threats to the integrity of the self then lead to a tendency to accentuate positive aspects of the self. PMID:26418357

  15. Locoregional post-mastectomy radiotherapy for breast cancer: literature review

    International Nuclear Information System (INIS)

    Postoperative radiotherapy is controversial after radical mastectomy. Recent clinical trials have shown an increase in survival with this irradiation and conclusions of previous meta-analyses should be reconsidered and conclusions of previous meta-analyses should be reconsidered. The results of a large number of randomized clinical trials in which women received post-mastectomy radiotherapy or not have been renewed. These trials showed a decrease in locoregional failure with the use of postoperative radiotherapy but survival advantages have not been clearly identified. A large number of randomized clinical trials compared postoperative radiotherapy alone, chemotherapy alone and the association of the two treatments. They showed that chemotherapy was less active locally than radiotherapy and that radiotherapy and chemotherapy significantly increased both disease-free and overall survival rates in the groups which received postoperative radiotherapy. These favourable results were, however, obtained with optimal radiotherapy techniques and a relative sparing of lung tissue and cardiac muscle. Many retrospective clinical analyses concluded that results obtained in locoregional failure rate were poor and that these failures led to an increase in future risks. Both radiotherapy and systemic treatment should be delivered after mastectomy, reserved for patients with a high risk of with a diameter ≥ 5 cm. However, radiotherapy could produce secondary effects, and techniques of radiotherapy should be optimal. (author)

  16. Successful treatment of one patient with advanced non-small cell lung cancer with icotinib hydrochloride in replacement of gefitinib%吉非替尼更换为盐酸埃克替尼成功治疗晚期非小细胞肺癌1例分享

    Institute of Scientific and Technical Information of China (English)

    张力; 关秋红; 赵艳伟; 夏莹; 肖毅

    2013-01-01

    表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)不良反应以皮疹、腹泻为主,吉非替尼(易瑞沙)和厄洛替尼分别于2005年和2007年在中国上市并获得了良好的疗效,但是仍然有部分可能获益的患者因不良反应而不能接受EGFR-TKI的治疗.盐酸埃克替尼(凯美纳)是我国研制的、具有完全自主知识产权的、高效特异性EGFR-TKI.本病例服用吉非替尼后出现Ⅲ~Ⅳ度腹泻,应用止泻药无效,患者因无法耐受停药.患者改用盐酸埃克替尼口服至今共7个月,未见明显不良反应,用药后1个月疗效评估:病情稳定(SD),体能状况、生活质量得到改善.说明盐酸埃克替尼治疗晚期非小细胞肺癌(NSCLC)具有较好的有效性、安全性和耐受性,与吉非替尼、厄洛替尼相比,疗效较优且不良反应较少.%Common adverse reactions of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) due to drug toxicity are rash and diarrhea.Positive curative effect has been observed after gefitinib (Iressa(R),ZD1839) and erlotinib (Tarceva(R),Ro50-8231) were introduced into China in 2005 and 2007,respectively.However,some patients who were likely to benefit from the therapy might not accept EGFR-TKIs because of severe adverse event (AE) during the treatment.Conmana(R) (icotinib hydrochloride,BPI-2009H) is a newly developed and highly specific EGFR-TKI that is designed in China with independent intellectual property right.In this case,the patient experienced Ⅲ ~ Ⅳ-level diarrhea after taking gefitinib,and antidiarrheal drugs were ineffective.The intolerable AE led to drug withdrawal.Treatment was then transformed into icotinib therapy and had been on for 7 months without apparent AE observed.After the first cycle of icotinib (30 days),objective responses were evaluated to be SD,physical conditions and the quality of life were improved.This suggests that icotinib is effective and well-tolerated in advanced NSCLC patients

  17. Physical treatment of lung cancer

    International Nuclear Information System (INIS)

    Trend of physical treatment and its outcome of lung cancer are described together with authors' experience. In locally advanced non-small cell lung cancer (NSCC) at stages IIIA and B, radiotherapy, chemotherapy (CT) and their combined therapy (RCT) have been major mainly in US since 1980s. After phase I/II trials of RCT by Okayama Lung Cancer Study Group where 5-year survival with nondisease is shown to be 31% (2003), phase III trial has been performed with results to be reported in 2008. A similar study by West Japan Oncology Group is now in summary. The secondary carcinogenesis not by radiation post RCT has become a problem: 10 years after, reportedly 61% incidence. Concerning the choice and regimen of CT medicals, there are many discussions. In recurrent/advanced NSCC, inhibitors of epidermal growth factor receptor tyrosine kinase (RTK) (gefitinib and recently, erlotinib) will be further useful, and molecular target medicals like an anti-vascular endothelial growth factor antibody (bevacizumab) and other novel RTK inhibitors will be also promising. In small cell lung cancer (SCC), efficacy 50% of amrubicin has been reported in a phase II trial recently. Prophylactic cranial irradiation in the extensive cases has been recognized effective also recently. CT studies with a large dose of anti-cancer drugs of SCC are still under progress. Along with the introduction of many molecular target drugs, physical treatment of lung cancer is to be bright in future. (R.T.)

  18. LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

    Science.gov (United States)

    Mura, M; Hopkins, T G; Michael, T; Abd-Latip, N; Weir, J; Aboagye, E; Mauri, F; Jameson, C; Sturge, J; Gabra, H; Bushell, M; Willis, A E; Curry, E; Blagden, S P

    2015-09-24

    RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression. PMID:25531318

  19. Reproductive history and pancreatic cancer incidence and mortality in a cohort of post-menopausal women

    OpenAIRE

    Stevens, Richard J.; Roddam, Andrew W; Green, Jane; Pirie, Kirstin; Bull, Diana; Reeves, Gillian K.; Beral, Valerie

    2009-01-01

    There is inconsistent evidence about the effect of reproductive history on women’s risk of pancreatic cancer. In the Million Women Study, a prospective cohort of middle-aged women in the UK, we examined associations between reproductive history and pancreatic cancer incidence and mortality, controlling for age, socioeconomic status, geographic region, body mass index, smoking and history of diabetes. During 7.1 million person-years of follow-up in 995,192 post-menopausal women there were 1,18...

  20. Vimentin and post-translational modifications in cell motility during cancer - a review.

    Science.gov (United States)

    Shi, A-M; Tao, Z-Q; Li, R; Wang, Y-Q; Wang, X; Zhao, J

    2016-07-01

    The post-translational modifications (PTMs) are defined as the covalent modification or enzymatic modification of proteins during or after protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signaling. Moreover, it is a known fact that PTM regulation offers an immense array and depth of regulatory possibilities. The present review article will focus on their possible role in cancer cell motility with special reference to vimentin, an intermediate filament (IF), as the later is an important process responsible for life-threatening state viz. cancer metastasis. PMID:27383311

  1. A meta-analysis of prevalence rates and moderating factors for cancer-related post-traumatic stress disorder

    OpenAIRE

    Abbey, Gareth; Thompson, Simon B N; Hickish, Tamas; Heathcote, David

    2014-01-01

    Objective Systematic reviews highlight a broad range of cancer-related post-traumatic stress disorder (CR-PTSD) prevalence estimates in cancer survivors. This meta-analysis was conducted to provide a prevalence estimate of significant CR-PTSD symptoms and full diagnoses to facilitate the psychological aftercare of cancer survivors. Methods A systematic literature search was conducted for studies using samples of cancer survivors by using validated clinical interviews and questionnaires to ass...

  2. Correlates and predictors of benefit finding and post-traumatic growth in Childhood cancer survivors

    Czech Academy of Sciences Publication Activity Database

    Koutná, Veronika; Blatný, Marek; Kepák, T.; Jelínek, Martin

    Lisabon: Wiley, 2014. 351-351. [16th World Congress of Psycho - oncology and Psycho social Academy. 20.10.2014-24.10. 2014, Lisabon] R&D Projects: GA ČR(CZ) GAP407/11/2421 Institutional support: RVO:68081740 Keywords : childhood cancer survivors * benefit finding * post-traumatic stress Subject RIV: AN - Psycho logy http://onlinelibrary.wiley.com/doi/10.1111/j.1099-1611.2014.3697/pdf

  3. [The Nutritional Care Experience of a Post-Operative Periampullary Cancer Patient With Cachexia].

    Science.gov (United States)

    Liou, Yan-Ting; Chiang, Pin-Yi; Shun, Shiow-Ching

    2016-04-01

    Cachexia is one of the most widely overlooked of the syndromes that are experienced by cancer patients. This syndrome is especially prevalent among patients with gastroenterology tract cancer. Although the National Comprehensive Cancer Network (NCCN) issued palliative-care practice guidelines for cachexia in 2015, guidelines have yet to be issued for the clinical setting. The authors reviewed the literature and applied their clinical experience to create an approach for identifying the degree of cachexia in a post-operative patient with periampullary cancer. This approach assesses the nutritional status, physical status, laboratory results, and gastrointestinal system functions of the patient using the Cachexia Assessment Scale (CAS) and NCCN Practice Guidelines for Cachexia. The patient improved under nursing care with an increase in nutritional intake and physical activity facilitating their process of post-surgical physical recovery. The authors hope that this experience using the combined CAS-NCCN Practice Guidelines will help clinical caregivers better understand how to apply the relevant guidelines in clinical settings. The developed approach may help nurses assess the comprehensive nutrition status of patients and related factors in order to provide interventions that will decrease the progression of cachexia effectively and promote quality of life. PMID:27026565

  4. Muc1 based breast cancer vaccines: role of post translational modifications

    International Nuclear Information System (INIS)

    Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

  5. Comparison of post contrast CT urography phases in bladder cancer detection

    International Nuclear Information System (INIS)

    The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment. (orig.)

  6. Comparison of post contrast CT urography phases in bladder cancer detection

    Energy Technology Data Exchange (ETDEWEB)

    Helenius, Malin; Dahlman, Par; Lonnemark, Maria; Magnusson, Anders [Uppsala University Hospital, Department of Surgical Sciences, Section of Radiology, Uppsala (Sweden); Brekkan, Einar [Uppsala University Hospital, Department of Surgical Sciences, Section of Urology, Uppsala (Sweden); Wernroth, Lisa [Uppsala University Hospital, Uppsala Clinical Research Center, Uppsala (Sweden)

    2016-02-15

    The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment. (orig.)

  7. The national cancer institute (NCI) and cancer biology in a 'post genome world'

    International Nuclear Information System (INIS)

    The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

  8. Optimizing the sequence of anti-EGFR targeted therapy in EGFR-mutant lung cancer

    OpenAIRE

    Meador, Catherine B.; Jin, Hailing; de Stanchina, Elisa; Nebhan, Caroline A.; Pirazzoli, Valentina; Wang, Lu; Lu, Pengcheng; Vuong, Huy; Hutchinson, Katherine E.; Jia, Peilin; Chen, Xi; Eisenberg, Rosana; Ladanyi, Marc; Politi, Katerina; Zhao, Zhongming

    2014-01-01

    Metastatic EGFR-mutant lung cancers are sensitive to the first- and second- generation EGFR tyrosine kinase inhibitors (TKIs), gefitinib, erlotinib, and afatinib, but resistance develops. Acquired resistance (AR) to gefitinib or erlotinib occurs most commonly (>50%) via the emergence of a second-site EGFR mutation, T790M. Two strategies to overcome T790M-mediated resistance are dual inhibition of EGFR with afatinib plus the anti-EGFR antibody, cetuximab (A+C), or mutant-specific EGFR inhibiti...

  9. Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative treatment in recurrent head and neck squamous cell carcinoma

    OpenAIRE

    Kushwaha, Vandana Singh; Gupta, Seema; Husain, Nuzhat; Khan, Huma; Negi, MPS; Jamal, Naseem; Ghatak, Ashim

    2015-01-01

    This study compared the efficacy and toxicity of Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil (5-FU) in patients of recurrent squamous cell carcinoma of head and neck (SCCHN) treated with palliative intent. Patients with recurrent SCCHN not amenable to curative treatment were randomly assigned to Gefitinib, Methotrexate or Methotrexate plus 5-FU arm. The primary end point was overall survival. Secondary end points of interest were objective response rate, toxicity and quality ...

  10. Inhibition of Intrahepatic Bile Duct Dilation of the Polycystic Kidney Rat with a Novel Tyrosine Kinase Inhibitor Gefitinib

    OpenAIRE

    Sato, Yasunori; Harada, Kenichi; Furubo, Shinichi; Kizawa, Kazuo; Sanzen, Takahiro; Yasoshima, Mitsue; Ozaki, Satoru; Isse, Kumiko; Sasaki, Motoko; Nakanuma, Yasuni

    2006-01-01

    The polycystic kidney (PCK) rat represents a liver and kidney cyst pathology corresponding to Caroli’s disease with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. We previously reported that an epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), significantly inhibited the abnormal growth of biliary epithelial cells of PCK rats in vitro. This study investigated the effects of gefitinib on cyst pathogenesis of the PCK rat both in vitr...

  11. Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients.

    Science.gov (United States)

    Wong, Chun-Kwok; Bao, Yi-Xi; Wong, Eliza Lai-Yi; Leung, Ping-Chung; Fung, Kwok Pui; Lam, Christopher Wai Kei

    2005-01-01

    Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p breast cancer patients. PMID:16047556

  12. Human cancer natural history, radiation induced immunodepression and post-operative radiation therapy

    International Nuclear Information System (INIS)

    For several types of cancers, post-operative radiation therapy is able to reduce the incidence of local recurrences, but has only a relatively small beneficial effect on total survival. Conversely to what has been claimed, this discrepancy is not due to a detrimental effect of radiotherapy. The data do not substantiate the hypothesis that irradiation through an impact on the immune system enhances growth of neoplastic foci outside of the irradiated volume. Several sets of data show that uncontrolled primary tumors or lymph node metastases can be important foci for distant spread. However, the analysis of the data shows that post-operative radiotherapy can prevent metastatic spread only in a small subset of patients, those without distant metastases at the initial treatment and in whom local recurrences can be a nidus for distant dissemination before being detected and treated. The results of the clinical trials carried out on patients with breast cancers show that this situation is frequently observed in patients with tumors located in the inner quadrants of the breast. The involvement of the internal mammary chain is relatively frequent in these patients

  13. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma.

    Science.gov (United States)

    Norden, Andrew D; Raizer, Jeffrey J; Abrey, Lauren E; Lamborn, Kathleen R; Lassman, Andrew B; Chang, Susan M; Yung, W K Alfred; Gilbert, Mark R; Fine, Howard A; Mehta, Minesh; Deangelis, Lisa M; Cloughesy, Timothy F; Robins, H Ian; Aldape, Kenneth; Dancey, Janet; Prados, Michael D; Lieberman, Frank; Wen, Patrick Y

    2010-01-01

    There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29-81) and median Karnofsky performance status (KPS) score 90 (range 60-100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. PMID:19562255

  14. Accumulation efficiency of cancer stem-like cells post γ-ray and proton irradiation

    International Nuclear Information System (INIS)

    Ionizing radiation (IR) has been proven to be a powerful medical treatment in cancer therapy. Rational and effective use of its killing power depends on understanding IR-mediated responses at the molecular, cellular and tissue levels. Increasing evidence supports that cancer stem-like cells (CSCs) play an important role in tumor regrowth and spread post radiotherapy, for they are resistant to various therapy methods including radiation. Presently, SW620 colon carcinoma monolayer culture cells were irradiated with γ-rays and protons of 2 Gy. Then apoptosis, clonogenic survival and the expression of CD133+ protein were examined. The results showed that there was no significantly difference either on long-term clonogenic survival or on short-term apoptosis ratio. However, compared with γ-rays, irradiation with protons was less efficient to accumulate CSCs at the same dose, although both protons and γ-rays can significantly accumulate the CD133+ CSCs subpopulation. In addition, the results of sphere formation assay also confirmed that proton irradiation is less efficient in CSCs accumulation, suggesting proton irradiation might have higher efficiency in CSCs elimination for cancer radiotherapy.

  15. Accumulation efficiency of cancer stem-like cells post γ-ray and proton irradiation

    Science.gov (United States)

    Quan, Yi; Wang, Weikang; Fu, Qibin; Mei, Tao; Wu, Jingwen; Li, Jia; Yang, Gen; Wang, Yugang

    2012-09-01

    Ionizing radiation (IR) has been proven to be a powerful medical treatment in cancer therapy. Rational and effective use of its killing power depends on understanding IR-mediated responses at the molecular, cellular and tissue levels. Increasing evidence supports that cancer stem-like cells (CSCs) play an important role in tumor regrowth and spread post radiotherapy, for they are resistant to various therapy methods including radiation. Presently, SW620 colon carcinoma monolayer culture cells were irradiated with γ-rays and protons of 2 Gy. Then apoptosis, clonogenic survival and the expression of CD133+ protein were examined. The results showed that there was no significantly difference either on long-term clonogenic survival or on short-term apoptosis ratio. However, compared with γ-rays, irradiation with protons was less efficient to accumulate CSCs at the same dose, although both protons and γ-rays can significantly accumulate the CD133+ CSCs subpopulation. In addition, the results of sphere formation assay also confirmed that proton irradiation is less efficient in CSCs accumulation, suggesting proton irradiation might have higher efficiency in CSCs elimination for cancer radiotherapy.

  16. The effect of progressive resistance training on lean body mass in post-treatment cancer patients - A systematic review

    DEFF Research Database (Denmark)

    Lønbro, Simon

    2014-01-01

    Loss of lean body mass is a common problem in many post-treatment cancer patients and may negatively affect physical capacity in terms of maximal muscle strength and functional performance. The purpose of this study was to systematically review the scientific evidence on the effect of progressive...... resistance training on lean body mass in post-treatment cancer patients. A comprehensive literature search was conducted and ultimately 12 studies were included. Methodological quality of the included studies was evaluated using the PEDro scale and the effect of progressive resistance training was reported...... 12 heterogenic studies there is moderate evidence supporting a positive effect of progressive resistance training on lean body mass in post-treatment cancer patients....

  17. AZD9291 in EGFR-mutant advanced non-small-cell lung cancer patients.

    Science.gov (United States)

    Remon, Jordi; Planchard, David

    2015-11-01

    Non-small-cell lung cancer (NSCLC) patients whose tumors have an EGFR-activating mutation develop acquired resistance after a median of 9-11 months from the beginning of treatment with erlotinib, gefitinib and afatinib. T790M mutation is the cause of this resistance in approximately 60% of cases. AZD9291 is an oral, irreversible, mutant-selective EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) developed to have potency against EGFR mutations, including T790M mutation, while sparing wild-type EGFR. A Phase I trial of AZD9291 in EGFR-mutant NSCLC patients, demonstrated high activity, essentially among T790M-mutant tumors, with a manageable tolerability profile. Ongoing Phase III trials are evaluating AZD9291 in EGFR-mutant patients as first-line treatment compared with erlotinib and gefitinib; and as second-line treatment compared with chemotherapy after progression on EGFR TKI in T790M-mutant tumors. Better identification of T790M-mutant tumors post EGFR TKI relapse and mechanisms of resistance to AZD9291 are the future challenges. This article reviews the emerging data regarding AZD9291 in the treatment of patients with advanced NSCLC. PMID:26450446

  18. Post-Traumatic Stress Disorder and Related Factors in Parents of Children With Cancer in South-East of Iran

    OpenAIRE

    Naderi, Majid; Firouzkoohi Moghadam, Mahboubeh; Hamzenejad, Mahdiyeh; Emamdadi, Abolfazl; Karami, Hossein

    2012-01-01

    Background Post-traumatic stress disorder (PTSD) comprises a collection of symptoms following exposure to injury-causing accidents of life. It is estimated that the prevalence of PTSD in children with malignancy and their parents is between 10-30% and even several years after treatment of malignancy this disorderremain in 20-20% of these patients. Objectives This study investigated the prevalence of post-traumatic stress disorder in parents of children with cancer. Materials and Methods In th...

  19. Studies on the Relationship between Neuroendocrine Cellular Differentiation in Gastric Cancers and Post-operative Survival Time

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To examine the ultrastructure of gastric cancer cells by the electron microscope, in order to assess the relationship between neuroendocrine differentiation and post-operative survival time.METHODS NSE, Syn and CgA immunohistochemical labeling was conducted in 168 cases with a common-type of gastric cancer. Electron microscopy was performed in 80 cases with positive immunohistochemical labeling.These cases were followed-up for over 5 years and the post-operative survival data analyzed.RESULTS Neuroendocrine granules were found by electron microscopy in 39 cases. The rate of neuroendocrine differentiation found was 23% (39/168), using routine diagnostic criteria and electron microscopy (REM).The post-operative survival time of gastric cancer patients with neuroendocrine differentiation was significantly shorter (P=0.0032) compared to those without neuroendocrine differentiation.CONCLUSION It is of significant clinical importance to determine if the neuroendocrine cells are differentiated in gastric cancers. The gastric cancer patients with neuroendocrine differentiation have a shorter post-operative survival time and a poorer prognosis. Electron microscopy is a reliable method of providing a diagnosis.

  20. Successful treatment of persistent bronchorrhea by gefitinib in a case with Recurrent Bronchioloalveolar Carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Shimono Takatsugu

    2003-07-01

    Full Text Available Abstract Background Bronchorrhea is one of late complaints in patients with bronchioloalveolar carcinoma (BAC and hampers their quality of life. Although an effective treatment for bronchorrhea in these patients has not been established, recently we have treated effectively one case of persistent bronchorrhea associated with clinical recurrent BAC with gefitinib (ZD1839, 'Iressa™'; AstraZeneca Japan; Osaka, Japan. Case Presentation A 63-year-old Japanese female had undergone left pneumonectomy with radical lymph node dissection (ND2a for diffuse type bronchioloalveolar carcinoma originated in left lower lobe. Multiple pulmonary metastases in right lung were found one year after operation. Pulmonary metastatic lesion has grown and she complained of progressive symptoms of massive watery sputum and dyspnea, four years after operation. Although her symptom was getting worse in spite of routine treatment, it completely disappeared within 2 weeks of starting oral gefitinib. Thereafter, she has been symptom-free and shows good partial response on repeat scan after 9 months of oral gefitinib. Conclusions The dramatic remission of persistent bronchorrhea by gefitinib in the presented case suggests that gefitinib might be a promising option for bronchioloalveolar carcinoma, particularly in cases with severe bronchorrhea. Although it is not possible to comment on whether the improvement came from tumor cell death itself or suppressive effect of mucin synthesis by the epidermal growth factor receptor-tyrosine kinase inhibitory action.

  1. 67 Scintigraphy shows altered colonic transit in patients post radiotherapy for prostatic cancer

    International Nuclear Information System (INIS)

    Full text: Radiotherapy (RTh) for prostatic cancer (CaP) frequently causes radiation proctitis with symptoms of diarrhoea, urgency and faecal incontinence. The contribution of altered colonic transit to these symptoms is not known. Colonic transit was therefore measured by scintigraphy following 4MBq oral 67Ga-citrate in 10 patients (56-81yr) undergoing RTh for CaP. Patients were studied 2 weeks before and at 1 and 12 months after RTh (dose 55-66Gy). Anterior and posterior abdominal scans were performed at 6, 24, 48 and 72 hours. Regions of interest and a composite image of the colon were derived and regional retention in the right and left colon and rectosigmoid region, colonic half clearance times and mean activity profiles determined using geometric mean data. Symptom severity was assessed using a validated questionnaire. There was an increase in stool frequency, faecal incontinence and urgency at 1 and 12 months post RTh (p<0.05). Although there was no difference in overall T1/2 there was reduced retention of tracer in the left colon (L) and rectosigmoid (R/S) region at 1 month with increased tracer retention in the right colon (R) at 1 and 12 months (p<0.05). Regional disturbances in colonic transit are seen in symptomatic patients post RTh for CaP that may contribute to acute symptoms with compensatory changes in the right colon. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  2. Merging technology and clinical research for optimized post-surgical rehabilitation of lung cancer patients

    Science.gov (United States)

    Brintnall, Ruth Ann; Cooper, Julie

    2016-01-01

    Background The 21st century has ushered in an age of wireless communication and technological breakthroughs providing researchers with opportunities and challenges as they incorporate this technology into their research. This paper presents the challenges our team encountered introducing new technologies and how they were overcome for an intervention for post-thoracotomy non-small cell lung cancer (NSCLC) patients. Methods Our intervention incorporated the Nintendo Wii Fit Plus virtual-reality walking and balance exercise into a home-based rehabilitation program. The intervention is novel and innovative in that the intervention provides light-intensity exercise post-thoracotomy for NSCLC patients immediately after return to home from the hospital. The intervention overcomes the barriers of conventional exercise programs that require travel, conventional exercise equipment, and begin months after surgery. Results When translating new technology to research, researchers need to consider a number of factors that need to be addressed. Institutional Review Boards may need further explanation as to why the technology is safe, potential participants may need to have unfounded concerns explained before enrolling, and the research team needs a plan for introducing the technology to participants with a vast range of skill sets and environments in which they will be using technology. In our study, we addressed each of these factors using varying approaches as we translated how the Wii would be used in a home-based exercise intervention by a highly vulnerable, post-thoracotomy NSCLC population. Conclusions While technology brings with it multiple barriers for successful implementation, our team showed that with proper planning and teamwork, researchers can navigate these issues bringing the full benefit of technology to even the most vulnerable of patient populations. PMID:26889481

  3. Positron Emission Tomography and head and neck cancers: Recurrence and post-treatment surveillance

    International Nuclear Information System (INIS)

    Recurrence of head and neck squamous cell carcinomas occurs early and currently, with poor prognosis. Post-therapeutic surveillance aims to diagnose a recurrence as early as possible in order to perform curative salvage therapy. The risk of recurrence is highest in locally advanced cancers. Morphological imaging, including Computed Tomography (CT Scan) and magnetic resonance imaging, can be limited by the anatomic changes following surgery and radiotherapy, and sometimes cannot provide early diagnosis of recurrence. Histology presents some risk of morbidity, especially in irradiated tissues, and sampling error. Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose (F.D.G.) is superior to conventional imaging for the diagnosis and staging of recurrence, especially when it is performed three months after the end of treatments. F.D.G.-PET has high sensitivity and negative predictive value for recurrence, so that further morphological and invasive investigations should not be performed in case of negative examination. On the other hand, because of its limited specificity and positive predictive value, any positive PET finding should be documented, in order to avoid false positives findings. The diagnosis of recurrence is the field of application in which F.D.G.-PET has the greatest impact on head and neck cancer management: it is considered as a standard. However, the interest of F.D.G.-PET during systematic follow-up has not yet been confirmed. PET should only be performed in difficult cases and within evaluation protocols. (authors)

  4. Meta-Analysis of First-Line Therapies in Advanced Non–Small-Cell Lung Cancer Harboring EGFR-Activating Mutations

    OpenAIRE

    Haaland, Benjamin; Tan, Pui San; Castro, Gilberto de; Lopes, Gilberto

    2014-01-01

    Introduction: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non–small-cell lung cancer harboring epidermal growth factor receptor–activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. Methods: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with ran...

  5. A one-year follow-up of post-traumatic stress disorder (PTSD) symptoms and perceived social support in cancer

    OpenAIRE

    Ballester Arnal, Rafael; Costa Requena, Gema; Gil Moncayo, Francisco; Qureshi, Adil

    2014-01-01

    Aims: Diagnosis of post-traumatic stress disorder (PTSD) symptoms in cancer patients fluctuates over the course of cancer according to the timing of assessment. In this longitudinal study, the prevalence of PTSD symptoms and the association between PTSD symptoms and the buffering variable of perceived social support were examined at one year follow-up. Procedure: People with different types of cancer were assessed (breast cancer, head and neck cancer, and colorectal tumor) on four occasions: ...

  6. Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation.

    Science.gov (United States)

    Zhang, Yalei; Yang, Haihong; Zhao, Meiling; He, Jianxing

    2012-06-01

    This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) was commenced. One week later, he was admitted under the impression of gefitinib-related interstitial pneumonitis, gefitinib was discontinued immediately and methylprednisolone with BIPAP assisted ventilation were used. The patient was followed up for 2 months after the start of treatment with corticosteroids and BIPAP assisted ventilation and remained well. PMID:22754672

  7. COMPARISON OF HYPOFRACTIONATED RADIATION THERAPY VERSUS CONVENTIONAL RADIATION THERAPY IN POST MASTECTOMY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Abhilash

    2016-03-01

    Full Text Available INTRODUCTION Breast cancer is the most common cancer in women worldwide and a leading cause of cancer death in females and accounts for 1.8 million new cases and approximately 0.5 million deaths annually. Patients who present with locally advanced breast cancer (LABC require multidisciplinary team approach that incorporates diagnostic imaging, surgery, chemotherapy and histopathological assessment, including molecular-based studies, radiation, and, if indicated, biologic and hormonal therapies. Hypofractionated radiation therapy following mastectomy has been used in many institutions for several decades and have demonstrated equivalent local control, cosmetic and normal tissues between 50 Gy in 25 fractions and various hypofractionated radiotherapy prescriptions employing 13-16 fractions. Evidence suggests that hypofractionated radiotherapy may also be safe and effective for regional nodal disease. AIMS AND OBJECTIVES To compare the local control and side effects of hypofractionated radiation therapy with conventional radiation therapy in post mastectomy carcinoma breast with stage II and III and to compare the tolerability and compliance of both schedules. MATERIALS AND METHODS The study was conducted on 60 histopathologically proven patients of carcinoma of breast, treated surgically with modified radical mastectomy. Group I patients were given external radiation to chest flap and drainage areas, a dose of 39 Gy/13 fractions/3.1 weeks, a daily dose 3 Gy for 13 fractions in 4 days a week schedule and Group II patients were given external radiation to chest flap and drainage areas, a dose of 50 Gy/25 fractions/5 weeks, to receive a daily dose 2 Gy for 25 fractions in a 5 days a week schedule. RESULTS The median age at presentation in Group I and II was 48 and 50 years respectively. Locoregional control after completion of radiotherapy in Group I vs. Group II was 26/30 (86.7% vs. 27/30 (90% respectively. Acute reactions and their grades in Group

  8. Protocol for a pilot randomised controlled trial of an online intervention for post-treatment cancer survivors with persistent fatigue

    Science.gov (United States)

    Corbett, Teresa; Walsh, Jane C; Groarke, AnnMarie; Moss-Morris, Rona; McGuire, Brian E

    2016-01-01

    Introduction Many post-treatment cancer survivors experience persistent fatigue that can disrupt attempts to resume normal everyday activities after treatment. Theoretical models that aim to explain contributory factors that initiate and sustain fatigue symptoms, or that influence the efficacy of interventions for cancer-related fatigue (CrF) require testing. Adjustment to fatigue is likely to be influenced by coping behaviours that are guided by the representations of the symptom. Objectives This paper describes the protocol for a pilot trial of a systematically and theoretically designed online intervention to enable self-management of CrF after cancer treatment. Methods and analysis This 2-armed randomised controlled pilot trial will study the feasibility and potential effectiveness of an online intervention. Participants will be allocated to either the online intervention (REFRESH (Recovery from Cancer-Related Fatigue)), or a leaflet comparator. Participants 80 post-treatment cancer survivors will be recruited for the study. Interventions An 8-week online intervention based on cognitive–behavioural therapy. Primary and secondary outcome measures The primary outcome is a change in fatigue as measured by the Piper Fatigue Scale (revised). Quality of life will be measured using the Quality of Life in Adult Survivors of Cancer Scale. Outcome measures will be collected at baseline, and at completion of intervention. Results The feasibility of trial procedures will be tested, as well as the effect of the intervention on the outcomes. Conclusions This study may lead to the development of a supportive resource to target representations and coping strategies of cancer survivors with CrF post-treatment. Setting Recruitment from general public in Ireland. Ethics and dissemination This trial was approved by the Research Ethics Committee at National University of Ireland Galway in January 2013. Trial results will be communicated in a peer-reviewed journal. Trial

  9. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    International Nuclear Information System (INIS)

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects

  10. Prostate-specific antigen (PSA) rate of decline post external beam radiotherapy predicts prostate cancer death

    International Nuclear Information System (INIS)

    Background and purpose: To assess the association between PSA velocity (PSAV) in the first 24 months after external beam radiotherapy (EBRT) and prostate cancer-specific mortality (PCSM) and all cause mortality. Materials and methods: All eligible patients in the South Australian (SA) Prostate Cancer Clinical Outcomes registry were followed. 848 Patients treated by definitive EBRT with more than one PSA recorded in the two year post-treatment were included. We calculated PSAV by linear regression. Results: The mean number of PSA measurements in the 2 year period was 4.4 (SD1.9). The median PSAVs across quartiles (Q1–Q4) were −4.17, −1.29, −0.38 and 0.20 ng/ml/yr. In multivariable analysis, a U-shaped relationship was seen between PSAV and PCSM with Q1–Q4 hazard ratios (HR) being 3.82 (1.46–10.00), 3.07 (1.10–8.58), 1, 5.15 (1.99–13.30) respectively. HR for all cause mortality in a similar model were 1.79 (1.07–2.98), 1.55 (0.93–2.59), 1.00 and 1.74 (1.04–2.90) for Q1 to Q4 respectively. A rapid PSA decline in the first year was a strong predictor of PCSM. However, in the second year PSA increase was positively associated with PCSM. Conclusion: A rapid decline in PSA in the first year following EBRT is positively associated with PCSM. This may be a useful early indicator of the need for additional therapies

  11. Psychosocial adjustments in patients with prostate cancer from pre-diagnosis to 6 months post-treatment.

    Science.gov (United States)

    Chien, Ching-Hui; Chuang, Cheng-Keng; Liu, Kuan-Lin; Huang, Xuan-Yi; Liu, Hsueh-Erh

    2016-02-01

    We evaluated changes in psychosocial adjustment over time and its associated factors in prostate cancer patients. A total of 69 patients with prostate cancer were surveyed at pre-diagnosis, 1 month and 6 months post-treatment. The questionnaires distributed to the patients consisted of the Psychosocial Adjustment to Illness Scale and the UCLA Prostate Cancer Index. The generalized estimating equations were used to analyse the collected data. The results of adjustments to psychological distress, the domestic environment and the social environment worsened post-treatment. However, the adjustment to health-care orientation was worst at the time of pre-diagnosis and improved during post-treatment. Patients who perceived an unfavourable health status reported poor adjustment in psychological distress. Patients exhibiting poor urinary function poorly adjusted to the domestic environment. Patients with sexual dysfunction exhibited poor adjustment to the social environment. Patients with low education demonstrated poor adjustment to health-care orientation. Further studies should assess the psychosocial adjustment among prostate cancer patients and provide interventions following pre-diagnosis. PMID:25307968

  12. Role of lung perfusion scintigraphy in predicting post-operative lung function in lung cancer patients undergoing pneumonectomy

    International Nuclear Information System (INIS)

    Full text: Surgery has been the mainstay of treatment for patients with early stage non-small cell lung cancer. There is an increased risk of postoperative complications, especially in patients with poor respiratory reserve, with pneumonectomy resulting in an unacceptable quality of life. The high risk of morbidity and mortality makes it mandatory to triage patients with anatomically resectable disease as suitable candidates for surgery. Aim: 1. The purpose of the study is to evaluate the role of lung perfusion scan in predicting postoperative lung function in lung cancer patients undergoing pneumonectomy based on the pre-operative Forced Expiratory Volume in 1 sec (FEV1). 2. The predicted post-operative FEV1 will be compared with the patient's lung function clinically based on a) number of days patient was on ventilation post-operatively, b) post-op respiratory complications/lung collapse. Materials and Methods: Imaging was done on Infinia Hawkeye (GE) dual headed gamma camera on 30 patients of lung cancer undergoing Pneumonectomy. Patients were injected 5 mCi of 99mTc-MAA and planar and tomographic images were obtained. A predicted postoperative value of FEV1 was calculated by the formula: postop predicted FEV1 = preop FEV1 - (FEV1 % contribution by affected lung/100). Patient's post-operative FEV1 was calculated for pneumonectomy. Patient was observed post-operatively and the following parameters were noted 1) Number of days patient was on ventilation post-operatively 2) Post-operative respiratory complications/lung collapse Pre-operative PFT's and 99mTc-MAA lung perfusion scan was done on 30 patients (mean age 45 yrs, range 18-64 yrs) and lung function in 1st week post-pneumonectomy based on their number of days on ventilation post-operatively and respiratory complications/lung collapse was noted. Result: 1) 20 patients underwent left pneumonectomy, 10 patients underwent right Pneumonectomy. 2) Predicted FEV1 for pneumonectomy patients was (mean ± SD 1.49 ± 0

  13. Sexual dysfunction in testicular cancer patients subjected to post-chemotherapy retroperitoneal lymph node dissection: a focus beyond ejaculation disorders.

    Science.gov (United States)

    Dimitropoulos, K; Karatzas, A; Papandreou, C; Daliani, D; Zachos, I; Pisters, L L; Tzortzis, V

    2016-05-01

    Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non-nerve-sparing PC-RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre-operatively and three months after RPLND, while post-operatively patients were asked to describe and evaluate changes in selected sexual parameters. Study findings demonstrate mixed pattern of changes in sexual functioning, with no difference in erectile functioning before and after operation. However, orgasmic function and intercourse and overall sexual satisfaction were found significantly impaired post-operatively. Sexual desire and frequency of attempted sexual intercourses were found significantly increased post-operatively, in comparison with pre-operative levels. With regard to patients' subjective perception on sexual functioning alterations after PC-RPLND, a significant number of patients reported higher levels of sexual desire, no difference in erectile function and worse orgasmic function and satisfaction post-operatively. Thus, patients subjected to PC-RPLND should be closely and routinely evaluated due to close relationship of sexual dissatisfaction with secondary psychological disorders. PMID:26268684

  14. Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy

    International Nuclear Information System (INIS)

    Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion. (authors)

  15. Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

    Science.gov (United States)

    2015-09-02

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

  16. Pneumatosis intestinalis and portal venous gas secondary to Gefitinib therapy for lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lee Joo

    2012-03-01

    Full Text Available Abstract Background Pneumatosis intestinalis (PI, defined as the presence of gas in the bowel wall, and portal venous gas (PVG are relatively rare radiological findings. Although several chemotherapeutic agents and anti-vascular endothelial growth factor agents are reported to be associated with PI and PVG, an association with anti-epidermal growth factor receptor (EGFR agents has not been described previously. Case presentation The present report describes a case of PI and PVG secondary to treatment with an EGFR tyrosine kinase inhibitor. A 66-year-old woman who had been diagnosed with metastatic lung adenocarcinoma presented with nausea, vomiting and abdominal distension after commencing gefitinib. A computed tomography (CT scan of the abdomen revealed PI extending from the ascending colon to the rectum, hepatic PVG, and infarction of the liver. Gefitinib therapy was discontinued immediately and the patient was managed conservatively. A follow-up CT scan 2 weeks later revealed that the PI and hepatic PVG had completely resolved. Conclusion This is the first report of PI and PVG caused by EGFR tyrosine kinase inhibitor. Although these complications are extremely rare, clinicians should be aware of the risk of PI and PVG in patients undergoing targeted molecular therapy.

  17. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected].

    NARCIS (Netherlands)

    Stewart, J.S.; Cohen, E.E.; Licitra, L.; Herpen, C.M.L. van; Khorprasert, C.; Soulieres, D.; Vodvarka, P.; Rischin, D.; Garin, A.M.; Hirsch, F.R.; Varella-Garcia, M.; Ghiorghiu, S.; Hargreaves, L.; Armour, A.; Speake, G.; Swaisland, A.; Vokes, E.E.

    2009-01-01

    PURPOSE: To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate. PATIENTS AND METHODS: Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral gef

  18. Pre- and Post-Operative Nomograms to Predict Recurrence-Free Probability in Korean Men with Clinically Localized Prostate Cancer

    OpenAIRE

    Minyong Kang; Chang Wook Jeong; Woo Suk Choi; Yong Hyun Park; Sung Yong Cho; Sangchul Lee; Seung Bae Lee; Ja Hyeon Ku; Sung Kyu Hong; Seok-Soo Byun; Hyeon Jeong; Cheol Kwak; Hyeon Hoe Kim; Eunsik Lee; Sang Eun Lee

    2014-01-01

    OBJECTIVES: Although the incidence of prostate cancer (PCa) is rapidly increasing in Korea, there are few suitable prediction models for disease recurrence after radical prostatectomy (RP). We established pre- and post-operative nomograms estimating biochemical recurrence (BCR)-free probability after RP in Korean men with clinically localized PCa. PATIENTS AND METHODS: Our sampling frame included 3,034 consecutive men with clinically localized PCa who underwent RP at our tertiary centers from...

  19. A prospective pilot study on the incidence of post-operative lymphedema in women with endometrial cancer

    Science.gov (United States)

    Hopp, Elizabeth E.; Osborne, Janet L.; Schneider, Deborah K.; Bojar, Claudia J.; Uyar, Denise S.

    2015-01-01

    To determine the incidence of lower-extremity lymphedema after surgical therapy including lymphadenectomy in endometrial cancer patients using standardized leg measurements. Also, to determine additional risk factors for the development of lymphedema and to study the effect of lymphedema on one's quality of life. In this prospective cohort study, patients with the diagnosis of endometrial cancer who were to undergo definitive surgical management were evaluated pre-operatively and followed post-operatively over the course of two years. Standardized leg measurements were performed by the same individuals at six time-points. Subjects also completed a standardized quality-of-life survey at each time-point. The incidence of lymphedema in 39 women with endometrial cancer using a standardized leg measurement protocol was 12.8% with lymphedema defined as a 20% increase in post-operative leg measurements. There was no significant association between the development of lymphedema and the number of pelvic or para-aortic lymph nodes removed, medical comorbidities, or surgical approach (p > 0.05). Of the five patients who met criteria for lymphedema, only one had worsening quality-of-life concerns post-operatively on the FACT-En, version 4, survey. This is the first prospective study using standardized leg measurements to calculate the incidence of post-operative lymphedema in endometrial cancer. Medical comorbidities, surgical approach, number of lymph nodes removed, and location of lymph nodes removed did not appear to affect the development of lymphedema in this cohort. A prospective, multicenter trial is needed to confirm these findings and to further assess the impact of lymphedema on one's quality of life. PMID:26937484

  20. Regional lung function impairment following post-operative radiotherapy for breast cancer using direct of tangential field techniques

    International Nuclear Information System (INIS)

    The effect of tangential and direct irradiation on regional lung function in 22 consecutive patients with breast cancer, treated by post-operative irradiation 3 months prior to examination. The tangential technique (total dose 32-36 Gy, 99Tcsup(m)-DTPA. Results were inconclusive, due to variable smoking habits. It is concluded that regional lung function was not significantly affected by the tangential technique, contrasting with a pronounced and harmful effect of the direct technique. (U.K.)

  1. Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Su; Kim, Sung Hoon; Park, Sonya Youngju; Park, Hye Lim; Seo, Ye Young; Choi, Woo Hee [The Catholic Univ. of Korea, Suwon (Korea, Republic of)

    2014-03-15

    The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients. We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups. Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %). Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p <0.05). The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic

  2. Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

    International Nuclear Information System (INIS)

    The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients. We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups. Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %). Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p <0.05). The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic

  3. The effect of progressive resistance training on lean body mass in post-treatment cancer patients – A systematic review

    International Nuclear Information System (INIS)

    Loss of lean body mass is a common problem in many post-treatment cancer patients and may negatively affect physical capacity in terms of maximal muscle strength and functional performance. The purpose of this study was to systematically review the scientific evidence on the effect of progressive resistance training on lean body mass in post-treatment cancer patients. A comprehensive literature search was conducted and ultimately 12 studies were included. Methodological quality of the included studies was evaluated using the PEDro scale and the effect of progressive resistance training was reported as the range of mean changes among RCTs and non-RCTs. Six RCTs and six non-RCTs were included in the study. In the RCTs the change in lean body mass in the progressive resistance training groups relative to control groups ranged from −0.4% to 3.9%, and in four of six trials the training effect was significantly larger than the change in the control groups. In the six non-RCTs, the mean change in lean body mass over time ranged from −0.01 to 11.8% which was significant in two of the trials. The included studies reported no or very limited adverse events following progressive resistance training. Based on 12 heterogenic studies there is moderate evidence supporting a positive effect of progressive resistance training on lean body mass in post-treatment cancer patients

  4. The Effects of Dinner-to-Bed Time and Post-Dinner Walk on Gastric Cancer Across Different Age Groups

    Science.gov (United States)

    Xu, Le; Zhang, Xi; Lu, Jun; Dai, Jia-Xi; Lin, Ren-Qin; Tian, Fang-Xi; Liang, Bing; Guo, Yi-Nan; Luo, Hui-Yu; Li, Ni; Fang, Dong-Ping; Zhao, Ruo-Hua; Huang, Chang-Ming

    2016-01-01

    Abstract Gastric cancer (GC) remains a major killer throughout the world. Despite the dramatic decrease in GC over the last century, its etiology has not yet been well characterized. This study investigated the possible independent and combined effects of the dinner-to-bed time and post-dinner walk on the risk for GC across different age groups. A population-based, case–control study was conducted in southeast China, including 452 patients with GC and 465 age-, race-, and gender-matched controls. A self-designed questionnaire was used to collect information on demographic characteristics, dinner-to-bed time, post-dinner walk, and other behavioral factors. Conditional logistic regression models were used to estimate the effects of the dinner-to-bed time and post-dinner walk as well as their joint effect on the risk for GC across different age groups. Individuals with dinner-to-bed time 55 years old. PMID:27100427

  5. A Study on the Pre-and Post-irradiation Effect of Blood Vessels in the Experimentally Induced Tongue Cancer

    International Nuclear Information System (INIS)

    The author observed the changes of vasculature of pre-and post-irradiation on DMBA induced rat tongue cancer. The study was performed by using vascular corrosion resin casting, and scanning electron microscopy. The results were as follows. 1. The capillaries runned parallely and formed bundles and, sometimes, plexus. The endothelial cells were arranged regularly and small pores were observed. 2. In irradiated normal tongue the capillaries were curved slightly and formed plexus on initial day of post-irradiation. On third day the capillaries and capillary pores were dilated and the endothelial cell arrangement was irregular. The effects of irradiation were gradually increased from initial to the 3rd day, though it was decreased after 7th day. 3. The vasculature of DMBA induced tongue cancer group were very irregular, and large avascular lesions were formed according to the cancer necrosis or tumor cell nest and the vasculature was narrowed and paralleled around the avascular lesion by compression of cancer cell nest. The vascular wall was roughened and dilated, forming club shaped or varix. 4. The vessels were curved and formed reticular network in irradiated DMBA induced tongue carinoma group. The free end of newly formed capillaries had regular width, and also irregular club shaped or aneurysmal dilation were observed. The vascular structures were destroyed and vessels were fused in tumor necrosis lesion. The radiation effects were marked on the first and third day of irradiation and the effects were decreased after seventh day and showed capillary regeneration.

  6. Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

    Directory of Open Access Journals (Sweden)

    Jay Ashokkumar Pandya

    2014-01-01

    Full Text Available Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months, and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining, fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.

  7. Neoadjuvant hormonal therapy is associated with comparable outcomes to neoadjuvant chemotherapy in post-menopausal women with estrogen receptor-positive breast cancer

    OpenAIRE

    Marcus, David M.; Switchenko, Jeffrey M.; Roshan ePrabhu; Ruth eO'Regan; Amelia eZelnak; Carolina eFasola; Donna eMister; Torres, Mylin A.

    2013-01-01

    Objectives: We compared outcomes in post-menopausal estrogen receptor-positive (ER+) breast cancer patients treated with neoadjuvant hormonal therapy (NAHT) or neoadjuvant chemotherapy (NACT).Methods: We retrospectively identified post-menopausal women who received either NAHT or NACT for non-metastatic, non-inflammatory, ER+, Her2neu negative breast cancer from 2004 to 2011. We compared long-term rates of locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS), ...

  8. Neoadjuvant Hormonal Therapy is Associated with Comparable Outcomes to Neoadjuvant Chemotherapy in Post-Menopausal Women with Estrogen Receptor-Positive Breast Cancer

    OpenAIRE

    Marcus, David M.; Switchenko, Jeffrey M.; Prabhu, Roshan; O’Regan, Ruth; Zelnak, Amelia; Fasola, Carolina; Mister, Donna; Torres, Mylin A.

    2013-01-01

    Objectives: We compared outcomes in post-menopausal estrogen receptor-positive (ER+) breast cancer patients treated with neoadjuvant hormonal therapy (NAHT) or neoadjuvant chemotherapy (NACT). Methods: We retrospectively identified post-menopausal women who received either NAHT or NACT for non-metastatic, non-inflammatory, ER+, Her2neu negative breast cancer from 2004 to 2011. We compared long-term rates of locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS),...

  9. Palliative chemotherapy in head and neck squamous cell cancer - What is best in Indian population? A time without symptoms, treatment toxicity score based study

    Directory of Open Access Journals (Sweden)

    V Anuradha

    2013-01-01

    Full Text Available Background: Patients with recurrent and metastatic head and neck Squamous Cell Cancer (HNSCC have poor prognosis with limited treatment options. In view of decimal prognosis, the treatment decision should include quality of life (QOL issues, cost-effectiveness besides the response rates and survival. Aim: Present retrospective analysis was conducted to evaluate efficacy (disease-free survival, pharmacoeconomics, and toxicity profile of four (4 different regimens, viz. gefitinib alone, gefitinib with methotrexate, methotrexate alone, or 5-FU with cisplatin. Materials and Methods: Case records between 2007 September and 2008 September were analyzed, 68 patients were found suitable for analysis. Patients received gefitinib (250 mg/day, methotrexate as 50 mg intramuscular weekly or a combination of the same or 5-FU 750 mg/m 2 /day for 4 days along with cisplatin 75 mg/m 2 /day on day 1 in 21-day cycle. Results: A total of 68 patients received therapy. Fifty-one patients have clinically meaningful response (stable disease + complete + partial responses (75% and had symptomatic improvement. The median progression-free survival was significantly superior in responders (those who achieved partial or complete response (8.4 months vs. 3.1 months, P=0.001. Methotrexate with gefitinib had maximum median survival and better overall QOL compared to the other treatment regimens. Weekly methotrexate is relatively cost-effective followed by methotrexate with gefitinib and gefitinib alone. 5-FU with cisplatin in our experience does not appear so attractive in view of high complication rates (when given in full doses and prolonged hospital stay. Conclusion: Based on the results of this retrospective analysis, methotrexate weekly as single agent or in combination with gefitinib appears as an attractive alternative regimen for patients with metastatic HNSCC including those having poor performance status. A prospective study was planned and submitted to the local

  10. Collaborative Research to Advance Precision Medicine in the Post-Genomic World | Office of Cancer Genomics

    Science.gov (United States)

    My name is Subhashini Jagu, and I am the Scientific Program Manager for the Cancer Target Discovery and Development (CTD2) Network at the Office of Cancer Genomics (OCG). In my new role, I help CTD2 work toward its mission, which is to develop new scientific approaches to accelerate the translation of genomic discoveries into new treatments. Collaborative efforts that bring together a variety of expertise and infrastructure are needed to understand and successfully treat cancer, a highly complex disease.

  11. Molecular mechanisms of cardiotoxicity of gefitinib in vivo and in vitro rat cardiomyocyte: Role of apoptosis and oxidative stress.

    Science.gov (United States)

    Korashy, Hesham M; Attafi, Ibraheem M; Ansari, Mushtaq A; Assiri, Mohammed A; Belali, Osamah M; Ahmad, Sheik F; Al-Alallah, Ibrahim A; Anazi, Fawaz E Al; Alhaider, Abdulqader A

    2016-06-11

    Gefitinib (GEF) is a multi-targeted tyrosine kinase inhibitor with anti-cancer properties, yet few cases of cardiotoxicity has been reported as a significant side effect associated with GEF treatment. The main purpose of this study was to investigate the potential cardiotoxic effect of GEF and the possible mechanisms involved using in vivo and in vitro rat cardiomyocyte model. Treatment of rat cardiomyocyte H9c2 cell line with GEF (0, 1, 5, and 10μM) caused cardiomyocyte death and upregulation of hypertrophic gene markers, such as brain natriuretic peptides (BNP) and Beta-myosin heavy chain (β-MHC) in a concentration-dependent manner at the mRNA and protein levels associated with an increase in the percentage of hypertrophied cardiac cells. Mechanistically, GEF treatment caused proportional and concentration-dependent increases in the mRNA and protein expression levels of apoptotic markers caspase-3 and p53 which was accompanied with marked increases in the percentage of H9c2 cells underwent apoptosis/necrosis as compared to control. In addition, oxidative stress marker (heme oxygenase-1, HO-1) and the formation of reactive oxygen species were increased in response to GEF treatment. At the in vivo level, treatment of Wistar albino rats for 21days with GEF (20 and 30mg/kg) significantly increased the cardiac enzymes (CK, CKmb, and LDH) levels associated with histopathological changes indicative of cardiotoxicity. Similarly, in vivo GEF treatment increased the mRNA and protein levels of BNP and β-MHC whereas inhibited the antihypertrophoic gene (α-MHC) associated with increased the percentage of hypertrophied cells. Furthermore, the mRNA and protein expression levels of caspase-3, p53, and HO-1 genes and the percentage of apoptotic cells were significantly increased by GEF treatment, which was more pronounced at the 30mg/kg dose. In conclusion, GEF induces cardiotoxicity and cardiac hypertrophy in vivo and in vitro rat model through cardiac apoptotic cell death

  12. Physical Distress, Emotional Status, and Quality of Life in Patients With Nasopharyngeal Cancer Complicated by Post-Radiotherapy Endocrinopathy

    International Nuclear Information System (INIS)

    Purpose: To explore factors affecting quality of life (QOL) among patients with nasopharyngeal cancer (NPC) complicated by post-radiotherapy endocrinopathy. Methods and Materials: This cross-sectional study was conducted in a tertiary medical center and involved a total of 43 post-radiotherapy, recurrence-free NPC patients with endocrinopathy. They performed self-assessment of their emotional status using the Beck Anxiety Inventory and Beck Depression Inventory-II, and their QoL with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire and the H and N35 cancer module. Results: Emotional and cognitive functioning of EORTC QLQ-C30 were the most affected. Fatigue, insomnia, and pain were the main concerns. Of the patients, 22 (51.2%) had anxiety and 19 (44.2%) had depression. Both depression and anxiety were negatively correlated with functional scales and global QoL but positively correlated with symptom scales. Multiple linear regression analysis revealed that physical distress symptoms of QLQ-C30 and physical functioning were the significant predictors of global QoL. Emotional and social functioning could predict depression, whereas emotional and physical functioning were significant predictors of anxiety. Conclusions: NPC patients with post-radiotherapy endocrinopathy exhibit impaired cognitive function and negative emotions. Symptoms of physical distress play an important role in QoL perception. Measurement of EORTC QLQ-C30 can be a useful instrument for the early detection of patients' impaired cognitive function and psychological morbidity. The high psychological distress related to the endocrine disturbances or the impact of NPC itself needs further study

  13. Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy

    Institute of Scientific and Technical Information of China (English)

    De-Chuan Chan; Kuo-Liang Shen; Yao-Chi Liu; Cheng-Jueng Chen; Jyh-Cherng Yu; Heng-Cheng Chu; Fa-Chang Chen; Teng-Wei Chen; Huan-Fa Hsieh; Tzu-Ming Chang

    2005-01-01

    AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy (IPC).METHODS: Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation (group A), and 16 did not (group B). Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group (group C). All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization.RESULTS: Gender, the type of resection, operating time,blood loss, tumor status and amount of narcotics were connparable in the three groups. However, the group C patients were older than those in groups A and B (67.5±17.7 vs 56.8±13.2, 57.5±11.7 years, P= 0.048). First bowel flatus occurred after 4.35±0.93 d in group A, 4.94±1.37 d in group B, and 4.71±1.22 d in group C (P>0.05). Oral feeding of a soft diet was tolerated 7.21±1.92 d after operation in group A, 10.15±2.17 d in group B, and 7.53±1.35 d in group C(groups A and C vsgroup B, P<0.05). There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients. Levels of C-reactive protein (CRP) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met.CONCLUSION: The results suggest that a combination of intravenous

  14. Breast cancer and mammography: knowledge, attitudes, practices and patient satisfaction post-mammography at the San Fernando General Hospital, Trinidad.

    Science.gov (United States)

    Gosein, Maria A; Pinto Pereira, Snehal M; Narinesingh, Dylan; Ameeral, Anthony

    2014-02-01

    Self-administered questionnaires were completed by 314 Trinidadian women, 40 years and older, to ascertain their breast cancer knowledge, attitudes, and practices. Those with higher education had greater knowledge of the benefits of early breast cancer detection (p breast cancer. Inaccurate beliefs particularly that breast compression causes cancer were more likely among those with the least education (p = .04). Obesity and alcohol were identified as risk factors by 29.3% and 12.4%, respectively. Over two-thirds (70%) of mammograms were primarily the doctor's decision. Over 90% of women were satisfied post-mammography, most (94.6%) with plans for future use. Some (15.6%) reported pain and 48.7% reported discomfort, with over 70% of these finding the examination less painful than anticipated. Targeted culturally sensitive awareness campaigns are needed. Clinicians must be sensitized to their importance in recommending mammography. Data on patient satisfaction and pain perception can be publicized to encourage women who are hesitant about mammography. PMID:24509017

  15. The Health Deviation of Post-Breast Cancer Lymphedema: Symptom Assessment and Impact on Self-Care Agency.

    Science.gov (United States)

    Armer, Jane M; Henggeler, Mary H; Brooks, Constance W; Zagar, Eris A; Homan, Sherri; Stewart, Bob R

    2008-01-01

    Breast cancer is the leading cancer among women world-wide, affecting 1 of 8 women during their lifetimes. In the US alone, some 2 million breast cancer survivors comprise 20% of all cancer survivors. Conservatively, it is estimated that some 20-40% of all breast cancer survivors will develop the health deviation of lymphedema or treatment-related limb swelling over their lifetimes. This chronic accumulation of protein-rich fluid predisposes to infection, leads to difficulties in fitting clothing and carrying out activities of daily living, and impacts self-esteem, self-concept, and quality of life. Lymphedema is associated with self-care deficits (SCD) and negatively impacts self-care agency (SCA) and physiological and psychosocial well-being. Objectives of this report are two-fold: (1) to explore four approaches of assessing and diagnosing breast cancer lymphedema, including self-report of symptoms and the impact of health deviations on SCA; and (2) to propose the development of a clinical research program for lymphedema based on the concepts of Self-Care Deficit Nursing Theory (SCDNT). Anthropometric and symptom data from a National-Institutes-of-Health-funded prospective longitudinal study were examined using survival analysis to compare four definitions of lymphedema over 24 months post-breast cancer surgery among 140 of 300 participants (all who had passed the 24-month measurement). The four definitions included differences of 200 ml, 10% volume, and 2 cm circumference between pre-op baseline and/or contralateral limbs, and symptom self-report of limb heaviness and swelling. Symptoms, SCA, and SCD were assessed by interviews using a validated tool. Estimates of lymphedema occurrence varied by definition and time since surgery. The 2 cm girth change provided the highest estimation of lymphedema (82% at 24 months), followed by 200 ml volume change (57% at 24 months). The 10% limb volume change converged with symptom report of heaviness and swelling at 24 months

  16. Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation

    OpenAIRE

    Zhang, Yalei; Haihong YANG; Zhao, Meiling; He, Jianxing

    2012-01-01

    This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) wa...

  17. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    International Nuclear Information System (INIS)

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC50). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: ► Non-responders had low EGFR expression, high PDGFR-β, and a low proliferation rate. ► PTEN is not indicative of response to a TKI. ► Erlotinib response was not associated with expression of the proteins examined. ► Imatinib-response correlated with expression of PDGFR-α. ► Gefitinib response correlated with increased expression of EGFR.

  18. Synergistic antitumor effect between gefitinib and fractionated irradiation in anaplastic oligodendrogliomas cannot be predicted by the Egfr signaling activity.

    OpenAIRE

    Sophie Pinel; Jihane Mriouah; Marc Vandamme; Alicia Chateau; François Plénat; Eric Guérin; Luc Taillandier; Valérie Bernier-Chastagner; Jean-Louis Merlin; Pascal Chastagner

    2013-01-01

    International audience In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment "gefitinib + radiotherapy" and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of a...

  19. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, Paula, E-mail: paula.kinsella@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Howley, Rachel, E-mail: rhowley@rcsi.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Doolan, Padraig, E-mail: padraig.doolan@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clarke, Colin, E-mail: colin.clarke@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Madden, Stephen F., E-mail: maddens@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clynes, Martin, E-mail: Martin.Clynes@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Farrell, Michael, E-mail: michaelfarrell@beaumont.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Amberger-Murphy, Verena, E-mail: Verena.Murphy@icorg.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); All Ireland Co-operative, Oncology Research Group, 60 Fitzwilliam Square, Dublin 2 (Ireland)

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC{sub 50}). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-{alpha} expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: Black-Right-Pointing-Pointer Non-responders had low EGFR expression, high PDGFR-{beta}, and a low proliferation rate. Black-Right-Pointing-Pointer PTEN is not indicative of response to a TKI. Black-Right-Pointing-Pointer Erlotinib response was not associated with expression of the proteins examined. Black-Right-Pointing-Pointer Imatinib-response correlated with expression of PDGFR-{alpha}. Black-Right-Pointing-Pointer Gefitinib response correlated with increased expression of EGFR.

  20. Concurrent chemoradiation with weekly Cisplatin, Docetaxel and Gefitinib: A study to assess feasibility, toxicity and immediate response

    OpenAIRE

    Prasad Eswaran; Kumaravelu S Azmi

    2013-01-01

    Objectives: Addition of docetaxel in the treatment regimen has shown improvement in survival of head and neck squamous cell carcinoma (HNSCC) patients. This study was conducted to evaluate the maximum tolerated dose of weekly docetaxel when combined with concurrent administration of weekly cisplatin, daily gefitinib, and radiation therapy. Materials and Methods: 21 patients with newly diagnosed HNSCC were included. Radiation therapy was planned to a dose of 66 Gy/33 fractions. Doses of ci...

  1. Concurrent chemoradiation with weekly Cisplatin, Docetaxel and Gefitinib: A study to assess feasibility, toxicity and immediate response

    Directory of Open Access Journals (Sweden)

    Prasad Eswaran

    2013-01-01

    Full Text Available Objectives: Addition of docetaxel in the treatment regimen has shown improvement in survival of head and neck squamous cell carcinoma (HNSCC patients. This study was conducted to evaluate the maximum tolerated dose of weekly docetaxel when combined with concurrent administration of weekly cisplatin, daily gefitinib, and radiation therapy. Materials and Methods: 21 patients with newly diagnosed HNSCC were included. Radiation therapy was planned to a dose of 66 Gy/33 fractions. Doses of cisplatin and gefitinib were kept constant at 30 mg/m 2 and 250 mg respectively. Dose of weekly docetaxel started with 5 mg/m 2 and escalated 5 mg/m 2 up to a maximum of 20 mg/m 2 . Serious adverse event was defined as grade 3/4 hematological and non-hematological toxicities. Results: All patients (three in dose level 1 [5 mg/m 2 ], level 2 [10 mg/m 2 ] and level 3 [15 mg/m 2 ] did not experience any hematological serious adverse events. Weekly docetaxel of 20 mg/m 2 could not be tolerated with the combination, and we encountered two hematological (neutropenia serious grade 4 adverse event and one grade 3 mucositis at level 4. Six patients were treated by omitting week 3 chemotherapy reducing the number of weekly cycles to a minimum of four. Gefitinib was continued throughout the treatment period. All patients tolerated the treatment well although with grade 2 hematological/non hematological toxicities. Conclusion: The maximal tolerated dose of weekly docetaxel added to weekly cisplatin and daily gefitinib during concurrent chemoradiation is 15 mg/m 2 . Toxicity profile is tolerable with a break in the chemotherapy regimen during radiation therapy. Aggressive nutritional support is essential prior to this regimen.

  2. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  3. From candidate gene studies to GWAS and post-GWAS analyses in breast cancer.

    Science.gov (United States)

    Fachal, Laura; Dunning, Alison M

    2015-02-01

    There are now more than 90 established breast cancer risk loci, with 57 new ones, revealed through genome-wide-association studies (GWAS) during the last two years. Established high, moderate and low penetrance genetic variants currently explain ∼49% of familial breast cancer risk. GWAS-discovered variants account for 14%, and it is estimated that another 1000 yet-to-be-discovered loci could contribute an additional ∼14% of familial risk. Polygenic risk scores can already be used to stratify breast cancer risk in the female population and could improve the targeting of mammographic screening programmes, which are at present largely based on age-specific risks. Fine-scale mapping and functional analyses are revealing candidate causal variants and the molecular mechanisms by which GWAS-hits may act. Better-powered GWAS and genome-wide sequencing projects are likely to continue identifying new breast cancer causal variants. PMID:25727315

  4. Development, implementation and evaluation of a multidisciplinary cancer rehabilitation programme : The CANSURVIVOR Project : meeting post-treatment cancer survivors’ needs

    LENUS (Irish Health Repository)

    Ivers, Mary E.

    2009-01-01

    Cancer survivor numbers in Ireland are increasing due to the success of modern treatments. Although most survivors have a good quality of life not all survivors return to \\'normal\\' after treatment. The HSE funded CANSURVIVOR research project has found that many survivors have difficulties and need help to recover and adjust after cancer treatment. Over a number of exploratory studies using interviews, focus groups and a survey of 262 breast, prostate, colorectal and lung cancer survivors, the researchers found that over 25% of survivors experienced significant difficulties with physical, emotional and social functioning, including symptoms such as insomnia and fatigue, while 33% experienced high levels of anxiety. Of particular concern were the findings that over 50% of survivors were overweight, 35% had reduced their physical activity levels and 13% continued to smoke after cancer, putting them at risk for further health problems. This evidence led to the development of an 8-week multi-disciplinary pilot rehabilitation programme. Significant quality of life improvements were achieved with increases in strength and fitness as well as a reduction in anxiety levels and dietary improvements. The researchers highlight the need for a structured, co-ordinated survivorship service, education of health professionals about survivorship and the provision of high quality information to survivors. This research was led by the School of Psychology at UCD in collaboration with the Physiotherapy and Nutrition departments of St. Vincent\\'s hospital.

  5. Obesity in post menopausal women with a family history of breast cancer: prevalence and risk awareness

    OpenAIRE

    Begum, Parvin; Richardson, Caroline E; Carmichael, Amtul R.

    2009-01-01

    Background: Obesity and physical activity are modifiable risk factors in the development of postmenopausal breast cancer. The aim of this study was to assess the level of awareness and prevalence of these factors in women attending family history clinics. Methods: Women attending the breast cancer family history clinic from 2004 to 2006 completed a questionnaire (SP15 format) about their knowledge of and exposure to various diet and lifestyle factors. All women had been counselled by a Co...

  6. Post-operative condition of breast cancer patients from standpoint of psycho-oncology: Preliminary results

    OpenAIRE

    Kovač Aleksandra; Popović-Petrović Svetlana; Nedeljković Miroslav; Kojić Marijana; Tomić Sanja

    2014-01-01

    Introduction. Information on being diagnosed to have cancer is always shocking for the patient, and it always causes a lot of psychosocial problems during its treatment. In these moments, patients need understanding, support and someone who can help them to apprehend all available options and choices clearly. The purpose of this study is to show the psychological states of patients with breast cancer after breast surgery, the importance of the psychological...

  7. Best Practice Guidelines in Assessment, Risk Reduction, Management, and Surveillance for Post-Breast Cancer Lymphedema

    OpenAIRE

    Jane M Armer; Jennifer M. Hulett; Bernas, Michael; Ostby, Pam; Stewart, Bob R.; Cormier, Janice N.

    2013-01-01

    Breast cancer-related lymphedema (LE) is a progressive, chronic disease that affects millions of cancer survivors and primarily results from surgical lymphatic vessel/node removal and radiation therapy. Patient education and support for importance of early detection is essential in helping health care providers detect lymphedema early, when there is the best chance to prevent progression. Improved imaging and surgical techniques have decreased the incidence of LE; however, effective risk-redu...

  8. Early Post Operative Enteral Versus Parenteral Feeding after Esophageal Cancer Surgery

    OpenAIRE

    Rajabi Mashhadi, Mohammad Taghi; Bagheri, Reza; Ghayour-Mobarhan, Majid; ZILAEE, Marzie; Rezaei, Reza; Maddah, Ghodratollah; Majidi, Mohamad Reza; Bahadornia, Mojgan

    2015-01-01

    Introduction: The incidence of malnutrition in hospitalized patients is reported to be high. In particular, patients with esophageal cancer are prone to malnutrition, due to preoperative digestive system dysfunctions and short-term non-oral feeding postoperatively. Selection of an appropriate method for feeding in the postoperative period is important in these patients. Materials and Methods: In this randomized clinical trial, 40 patients with esophageal cancer who had undergone esophagectomy...

  9. Transcriptional and post-transcriptional regulation of Sprouty1, a receptor tyrosine kinase inhibitor in prostate cancer.

    Science.gov (United States)

    Darimipourain, M; Wang, S; Ittmann, M; Kwabi-Addo, B

    2011-12-01

    Sprouty1 (Spry1) is a negative regulator of fibroblast growth factor signaling with a potential tumor suppressor function in prostate cancer (PCa). Spry1 is downregulated in human PCa, and Spry1 expression can markedly inhibit PCa proliferation in vitro. We have reported DNA methylation as a mechanism for controlling Spry1 expression. However, promoter methylation does not seem to explain gene silencing in all PCa cases studied to suggest other mechanisms of gene inactivation, such as alterations in trans-acting factors and/or post-transcriptional activity may be responsible for the decreased expression in those cases. Binding sites for Wilm's tumor (WT1) transcription factors EGR1, EGR3 and WTE are highly conserved between the mouse and human Spry1 promoter regions, suggesting an evolutionary conserved mechanism(s) involving WT1 and EGR in Spry1 regulation. Spry1 mRNA contains multiple microRNA (miRNA) binding sites in its 3'UTR region suggesting post-transcriptional control. We demonstrate that Spry1 is a target for miR-21-mediated gene silencing. miRNA-based therapeutic approaches to treat cancer are emerging. Spry1 is highly regulated by miRNAs and could potentially be an excellent candidate for such approaches. PMID:21826097

  10. Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study

    International Nuclear Information System (INIS)

    Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer. We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined. Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, P = 0.027). These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer

  11. Clinical Study on Early Post-operational Intraperitoneal Chemotherapy and Salviae in Treating Patients of Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    于庆生; 王炜; 汪小明; 王汉明; 帅剑峰

    2002-01-01

    Objective: To evaluate the safety, feasibility and short-term efficacy of early post-operational intraperitoneal chemotherapy (EPIC) combined with Salviae miltiorrhizae (SM) in treating patients with gastric cancer. Methods: The 136 patients enrolled were divided into 3 groups: the EPIC group, the EPVC group and the control group. The former two groups were treated with SM plus 5-FU started from the second or third day after operation for 5 continuous days by intraperitoneal infusion or intravenous dripping respectively, and the control group was untreated but conventional chemotherapy was given 3 weeks after surgical operation. Toxic and adverse effects of chemotherapy, post-operational complications, short-term survival rate and intra-abdominal tumor recurrence rate were observed and compared.Results: (1) Toxic adverse effects of chemotherapy that occurred in the EPIC group were less than those in the EPVC group significantly (P<0.05-0.01). (2) Occurrence of serious complications in the EPIC group was not higher than that in the other two groups. (3) The 1- and 2-year survival rate in the EPIC group was higher than those in the other two groups respectively (P<0.01), while the post-operational intra-abdominal recurrence rate in EPIC group was significantly lower than that in the other two groups (P<0.05). Conclusions: Combined therapy of SM and 5-FU in treating patients with gastric cancer by intraperitoneal infusion is not only safe and feasible with mild toxic and side effect, but also produces a more beneficial effects, including less intra-abdominal recurrence and satisfactory short-term survival rate .

  12. Pre- and post-operative nomograms to predict recurrence-free probability in korean men with clinically localized prostate cancer.

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    Full Text Available OBJECTIVES: Although the incidence of prostate cancer (PCa is rapidly increasing in Korea, there are few suitable prediction models for disease recurrence after radical prostatectomy (RP. We established pre- and post-operative nomograms estimating biochemical recurrence (BCR-free probability after RP in Korean men with clinically localized PCa. PATIENTS AND METHODS: Our sampling frame included 3,034 consecutive men with clinically localized PCa who underwent RP at our tertiary centers from June 2004 through July 2011. After inappropriate data exclusion, we evaluated 2,867 patients for the development of nomograms. The Cox proportional hazards regression model was used to develop pre- and post-operative nomograms that predict BCR-free probability. Finally, we resampled from our study cohort 200 times to determine the accuracy of our nomograms on internal validation, which were designated with concordance index (c-index and further represented by calibration plots. RESULTS: Over a median of 47 months of follow-up, the estimated BCR-free rate was 87.8% (1 year, 83.8% (2 year, and 72.5% (5 year. In the pre-operative model, Prostate-Specific Antigen (PSA, the proportion of positive biopsy cores, clinical T3a and biopsy Gleason score (GS were independent predictive factors for BCR, while all relevant predictive factors (PSA, extra-prostatic extension, seminal vesicle invasion, lymph node metastasis, surgical margin, and pathologic GS were associated with BCR in the post-operative model. The c-index representing predictive accuracy was 0.792 (pre- and 0.821 (post-operative, showing good fit in the calibration plots. CONCLUSIONS: In summary, we developed pre- and post-operative nomograms predicting BCR-free probability after RP in a large Korean cohort with clinically localized PCa. These nomograms will be provided as the mobile application-based SNUH Prostate Cancer Calculator. Our nomograms can determine patients at high risk of disease recurrence

  13. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Background and purpose: To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT). Materials and methods: Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25 Gy/10 fractions) and chest RT (40 Gy/15 fractions) were given simultaneously 4–8 weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival. Results: Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3 months, respectively (median follow-up = 21.8 months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic. Conclusions: Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.

  14. Identifying MRI markers to evaluate early treatment-related changes post-laser ablation for cancer pain management

    Science.gov (United States)

    Tiwari, Pallavi; Danish, Shabbar; Madabhushi, Anant

    2014-03-01

    Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment modality for cancer pain management that targets the cingulum (pain center in the brain), and has shown promise over radio-frequency (RF) based ablation which is reported to provide temporary relief. One of the major advantages enjoyed by LITT is its compatibility with magnetic resonance imaging (MRI), allowing for high resolution in vivo imaging to be used in LITT procedures. Since laser ablation for pain management is currently exploratory and is only performed at a few centers worldwide, its short-, and long-term effects on the cingulum are currently unknown. Traditionally treatment effects are evaluated by monitoring changes in volume of the ablation zone post-treatment. However, this is sub-optimal since it involves evaluating a single global parameter (volume) to detect changes pre-, and post-MRI. Additionally, the qualitative observations of LITT-related changes on multi-parametric MRI (MPMRI) do not specifically address differentiation between the appearance of treatment related changes (edema, necrosis) from recurrence of the disease (pain recurrence). In this work, we explore the utility of computer extracted texture descriptors on MP-MRI to capture early treatment related changes on a per-voxel basis by extracting quantitative relationships that may allow for an in-depth understanding of tissue response to LITT on MRI, subtle changes that may not be appreciable on original MR intensities. The second objective of this work is to investigate the efficacy of different MRI protocols in accurately capturing treatment related changes within and outside the ablation zone post-LITT. A retrospective cohort of studies comprising pre- and 24-hour post-LITT 3 Tesla T1-weighted (T1w), T2w, T2-GRE, and T2-FLAIR acquisitions was considered. Our scheme involved (1) inter-protocol as well as inter-acquisition affine registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters

  15. Post-radiation malignant fibrous histiocytoma following treatment of breast cancer: A case report

    International Nuclear Information System (INIS)

    Post-radiation malignant fibrous histiocytoma (MFH) of the breast is extremely rare. We report a case of post-radiation MFH that presented a rapidly growing mass in a 52-year-old woman who underwent breast-conserving therapy and adjuvant whole breast irradiation 6 years ago. To the best of our knowledge, only one case of primary MFH of the female breast have been reported with sonographic findings. We analyzed the sonographic and MRI findings with correlative histopathologic features, and then confirmed with surgical excision.

  16. Predicting post-treatment survivability of patients with breast cancer using Artificial Neural Network methods.

    Science.gov (United States)

    Wang, Tan-Nai; Cheng, Chung-Hao; Chiu, Hung-Wen

    2013-01-01

    In the last decade, the use of data mining techniques has become widely accepted in medical applications, especially in predicting cancer patients' survival. In this study, we attempted to train an Artificial Neural Network (ANN) to predict the patients' five-year survivability. Breast cancer patients who were diagnosed and received standard treatment in one hospital during 2000 to 2003 in Taiwan were collected for train and test the ANN. There were 604 patients in this dataset excluding died not in breast cancer. Among them 140 patients died within five years after their first radiotherapy treatment. The artificial neural networks were created by STATISTICA(®) software. Five variables (age, surgery and radiotherapy type, tumor size, regional lymph nodes, distant metastasis) were selected as the input features for ANN to predict the five-year survivability of breast cancer patients. We trained 100 artificial neural networks and chose the best one to analyze. The accuracy rate is 85% and area under the receiver operating characteristic (ROC) curve is 0.79. It shows that artificial neural network is a good tool to predict the five-year survivability of breast cancer patients. PMID:24109931

  17. Post-laryngectomy voice rehabilitation with a voice prosthesis in a young girl with advanced thyroid cancer.

    Science.gov (United States)

    Fukuhara, Takahiro; Miyoshi, Masayuki; Fujii, Taihei; Miyake, Naritomo; Taira, Kenkichiro; Koyama, Satoshi; Taguchi, Daizo; Fujiwara, Kazunori; Kataoka, Hideyuki; Kitano, Hiroya; Takeuchi, Hiromi

    2016-10-01

    The aim of this report is to evaluate the effects of voice rehabilitation with a voice prosthesis in a young patient with thyroid cancer. A 17-year-old girl underwent voice restoration with a voice prosthesis after laryngectomy to treat thyroid cancer. She completed voice-related questionnaires (the Voice Handicap Index-10 and Voice-Related Quality Of Life Survey) at ages 17 and 21 and underwent phonetic functional evaluation. The sound spectrograms of her phonation using the voice prosthesis showed low frequency sounds without an obvious basic frequency. She was ashamed of her hoarse voice and did not use her voice prosthesis during high school. However, after beginning to work at age 20, she used her voice to communicate in the workplace. At age 21, her questionnaire scores, especially those related to the physical and functional domains, improved compared with those at age 17. Voice restoration with a voice prosthesis is recommended for young patients who undergo laryngectomy for advanced thyroid cancer. The advantages of voice restoration with a voice prosthesis may increase when the patient reaches working age, and it may improve post-laryngectomy quality of life considerably. PMID:26960746

  18. Association between Soy Isoflavone Intake and Breast Cancer Risk for Pre- and Post-Menopausal Women: A Meta-Analysis of Epidemiological Studies

    OpenAIRE

    Meinan Chen; Yanhua Rao; Yi Zheng; Shiqing Wei; Ye Li; Tong Guo; Ping Yin

    2014-01-01

    BACKGROUND: Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intak...

  19. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald; Knoop, Ann S; Ditzel, Henrik J

    2014-01-01

    alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...... design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis and...

  20. Application of microvascular free osteocutaneous flaps in the management of post-radiation recurrent oral cancer

    International Nuclear Information System (INIS)

    Fifty-nine patients underwent free flap osteocutaneous reconstruction that consisted of flaps of the dorsum of the foot in 26 patients and iliac crest flaps in 33 with a success rate of 92 percent and a mortality rate of 1.6 percent. These flaps, which require the expertise of microvascular surgeons, are time-consuming and complicate operating room and time management, but they represent a remarkable advance in reconstruction that can facilitate cosmetic and functional recovery of the patient. In particular, they promote healing in radiation-recurrent oral cancer and represent a definitive form of management for established radionecrosis of the mandible. The large volume of tissue available with iliac crest osteocutaneous grafts permits the management of patients with extensive cancer involving the skin, mucosa, and bone, but cancer control may still be disappointing and there is a need for improved adjuvant chemotherapy protocols. This technique appears to be a dependable, repeatable, and significant advance in management of the patient with head and neck cancer

  1. Refining Post-Surgical Therapy for Women with Lymph Node-Positive Breast Cancer

    Science.gov (United States)

    In this trial, women with HER2-negative, HR-positive breast cancer and 1-3 positive lymph nodes with recurrence scores of 25 or lower will be randomized to undergo adjuvant chemotherapy before starting endocrine therapy or to begin endocrine therapy.

  2. Post-operative condition of breast cancer patients from standpoint of psycho-oncology: Preliminary results

    Directory of Open Access Journals (Sweden)

    Kovač Aleksandra

    2014-01-01

    Full Text Available Introduction. Information on being diagnosed to have cancer is always shocking for the patient, and it always causes a lot of psychosocial problems during its treatment. In these moments, patients need understanding, support and someone who can help them to apprehend all available options and choices clearly. The purpose of this study is to show the psychological states of patients with breast cancer after breast surgery, the importance of the psychological support, and first experiences in psycho-oncological management of breast cancer patients. Material and Methods. The study sample included 46 women, their average age being 52.32 (± 8.98, who had answered questions in a questionnaire in the period after surgery. Results. The patients experienced fears and worries associated with almost every part of cancer treatment likely to happen in the near future. The fear of chemotherapy and radiotherapy (67%, the horror of losing hair (59% and the fear of relapse or disease progression (57% were evident. Moreover, the patients dreaded the forthcoming pathological results and the decisions to be made by the Oncology Commission (57%, with accompanying insomnia caused by disturbing thoughts in 39% of the patients. Conclusion. These findings suggest that psychological support is important in this early period after breast surgery due to the vulnerability of the patients, and because it can diminish the risk of potential escalation of distress.

  3. Application of microvascular free osteocutaneous flaps in the management of post-radiation recurrent oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, I.B.; Manktelow, R.T.; Zuker, R.M.; Boyd, B.

    1985-10-01

    Fifty-nine patients underwent free flap osteocutaneous reconstruction that consisted of flaps of the dorsum of the foot in 26 patients and iliac crest flaps in 33 with a success rate of 92 percent and a mortality rate of 1.6 percent. These flaps, which require the expertise of microvascular surgeons, are time-consuming and complicate operating room and time management, but they represent a remarkable advance in reconstruction that can facilitate cosmetic and functional recovery of the patient. In particular, they promote healing in radiation-recurrent oral cancer and represent a definitive form of management for established radionecrosis of the mandible. The large volume of tissue available with iliac crest osteocutaneous grafts permits the management of patients with extensive cancer involving the skin, mucosa, and bone, but cancer control may still be disappointing and there is a need for improved adjuvant chemotherapy protocols. This technique appears to be a dependable, repeatable, and significant advance in management of the patient with head and neck cancer.

  4. The Impact of Post-Mastectomy Radiation Therapy on Male Breast Cancer Patients—A Case Series

    International Nuclear Information System (INIS)

    Objective: To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP). Methods and Materials: Men with a diagnosis of breast cancer referred to LRCP were reviewed. The seventh American Joint Committee on Cancer staging system was used. Patients treated with and without post-mastectomy radiation therapy (PMRT) were analyzed. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. Survival estimates were obtained using Kaplan-Meier methodology. Results: From January 1977 to December 2006, 81 men had invasive ductal carcinoma. The median age was 65 (range, 35–87 years). There were 15 Stage I, 40 Stage II, 20 Stage III, and 6 Stage IV patients. Median follow-up time was 46 months (range, 1–225 months). Of the 75 patients treated with curative intent, 29 did not receive PMRT and 46 completed PMRT. Patients who received PMRT demonstrated no benefit in overall survival (p = 0.872) but significantly better local recurrence free survival (p < 0.001) compared with those who did not receive RT. There was trend toward improving locoregional recurrence with PMRT in patients with high-risk features (node-positive, advanced stage, and ≤2 mm or unknown surgical margin). The median, 5-year, and 10-year disease-free survival and overall survival for the 75 patients were 77.7 months, 66.3%, 32.7%, and 91.2 months, 73.9%, and 36.6%, respectively. Conclusion: The experience at LRCP suggests that high-risk MBC patients should consider PMRT to improve their chance of local recurrence-free survival.

  5. Treatment of gastric remnant cancer post distal gastrectomy by endoscopic submucosal dissection using an insulation-tipped diathermic knife

    Institute of Scientific and Technical Information of China (English)

    Shoji Hirasaki; Hiromitsu Kanzaki; Minoru Matsubara; Kohei Fujita; Shuji Matsumura; Seiyuu Suzuki

    2008-01-01

    AIM: To evaluate the effectiveness of endoscopic submucosal dissection using an insulation-Upped diathermic knife (IT-ESD) for the treatment of patients with gastric remnant cancer.METHODS: Thirty-two patients with early gastric cancer in the remnant stomach, who underwent distal gastrectomy due to gastric carcinoma, were treated with endoscopic mucosal resection (EMR) or ESD at Sumitomo Besshi Hospital and Shikoku Cancer Center in the 10-year period from January 1998 to December 2007, including 17 patients treated with IT-ESD.Retrospectively, patient backgrounds, the one-piece resection rate, complete resection (CR) rate, operation time, bleeding rate, and perforation rate were compared between patients treated with conventional EMR and those treated with IT-ESD.RESULTS- The CR rate (40% in the EMR group ys 82% in the IT-ESD group) was significantly higher in the IT-ESD group than in the EMR group; however,the operation time was significantly longer for the ITESD group (57.6±31.9 min vs 21.1±12.2 min).No significant differences were found in the rate of underlying cardiopulmonary disease (IT-ESD group, 12% ys EMR group, 13%), one-piece resection rate (100% vs 73%), bleeding rate (18% vs 6.7%), and perforation rate (0% vs 0%) between the two groups.CONCLUSION: IT-ESD appears to be an effective treatment for gastric remnant cancer post distal gastrectomy because of its high CR rate.It is useful for histological confirmation of successful treatment.The long-term outcome needs to be evaluated in the future.

  6. Histomorphological study of tissues and cancers in post-radiotherapy - K.S. Hegde Medical Academy experience

    International Nuclear Information System (INIS)

    With increasing use of radiation therapy in cancer treatment and longer survival of patients, assessment of radiation associated changes in tissues and tumours has become an important issue in modern pathology. Besides killing tumour cells, therapeutic radiation also damages normal tissues and sometimes induces malignancies. Radiation associated changes can pose important diagnostic pitfalls in pathological assessment and therefore deserve more attention. This study aims to identify the radiation induced histomorphological changes in normal tissues and cancers. This is a retrospective study, conducted at K.S. Hegde Medical Academy between 2008 to 2013, in which all post-radiotherapy cases who presented to K.S. Hegde Medical Academy were included. A total of 24 cases were collected and morphological changes were studied. Out of total 24 cases, squamous cell carcinoma was identified in 14 cases, different grades of dysplasia in 5 cases and rest had other radiation induced changes. Most common site of lesion was Head and Neck in 20/24 cases. Irradiated native cells were characterized by nuclear and cytoplasmic enlargement, associated with degenerative changes i.e. necrosis and fibrosis. Tumour cells showed poor differentiation in 7/14 cases, moderate differentiation in 3/14 cases and remaining 4 had well differentiation. Severe dysplasia was seen in one case while mild to moderate dysplasia in 4/5 cases. Radiation will continue to increase in importance in the diagnosis and treatment of disease. For this reason considerable emphasis is placed on the biologic basis for the use of radiation in the treatment of malignant tumours. To conclude, as new cancer treatments are developed, it is essential to investigate their short as well as long term consequences, because quality of life must also be considered along with the therapeutic efficacy of cancer treatment. (author)

  7. Post-operative radiation therapy for advanced head and neck cancers

    International Nuclear Information System (INIS)

    Purpose: To discuss both general and specific indications for radiation following surgery for patients with cancers of the head and neck. Patients with advanced cancers of the head and neck are often not suitable candidates for treatment with definitive radiation, and are treated with surgery. Frequently these patients fail by recurring in either the primary sites or in the necks. Adjuvant radiation is therefore often a critical component in the management of these patients. While radiation can be done either prior to or after surgery, most centers prefer the postoperative setting. This refresher course will review general concepts of postoperative irradiation for the patient with head and neck cancer and apply these concepts to specific situations. The course will begin with a broad review of the indications for postoperative irradiation as not all patients undergoing surgery for cancers of the head and neck require additional treatment. We will also review the concept of using postoperative radiation to allow for more conservative surgery with preservation of function. The second portion of the course will focus on general techniques of postoperative irradiation. We will review concepts of patient setup and treatment portal design and describe how specific techniques are practiced at MDACC. Controversial topics, including field matching, total dose and fractionation, and the timing of postoperative radiation will be discussed. The final section of the course will review the results of postoperative irradiation as applied to the head and neck in general as well as to specific subsites. In addition to results for the common scenarios of squamous cell carcinomas of the oral cavity, pharynx and larynx, we will review results of postoperative irradiation for skin cancers of the head and neck, paranasal sinuses, and salivary glands

  8. Diffuse pulmonary metastases with negative 18FDG positron emission tomography/computed tomography and positive post-radioiodine therapy scan of papillary thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    LIN Yan-song; LIANG Zhi-yong; QIU Li-heng; CHENG Xin

    2012-01-01

    A female papillary thyroid cancer patient with diffuse micronodular pulmonary metastases was confirmed only by post radioactive iodine (RAI) therapy whole body scan (RxWBS).Her diagnostic iodine-131 whole body scan (DxWBS),chestCT and 18FDG PET/CT scan were all negative.Attention and pitfalls of this case concerning surgical and RAI dosemanagement are against current international guidelines on thyroid cancer.

  9. EGFR Transactivation by Peptide G Protein-Coupled Receptors in Cancer.

    Science.gov (United States)

    Moody, Terry W; Nuche-Berenguer, Bernardo; Nakamura, Taichi; Jensen, Robert T

    2016-01-01

    Lung cancer kills approximately 1.3 million citizens in the world annually. The tyrosine kinase inhibitors (TKI) erlotinib and gefitinib are effective anti-tumor agents especially in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. The goal is to increase the potency of TKI in lung cancer patients with wild type EGFR. G protein-coupled receptors (GPCR) transactivate the wild type EGFR in lung cancer cells. The GPCR can be activated by peptide agonists causing phosphatidylinositol turnover or stimulation of adenylylcyclase. Recently, nonpeptide antagonists were found to inhibit the EGFR transactivation caused by peptides. Nonpeptide antagonists for bombesin (BB), neurotensin (NTS) and cholecystokinin (CCK) inhibit lung cancer growth and increase the cytotoxicity of gefitinib. The results suggest that GPCR transactivation of the EGFR may play an important role in cancer cell proliferation. PMID:25563590

  10. Overprotective caregivers of elderly cancer patients: a case report.

    Science.gov (United States)

    Basso, Umberto; Brunello, Antonella; Magro, Cristina; Favaretto, Adolfo; Monfardini, Silvio

    2006-01-01

    The essential role of the caregiver in the management of elderly cancer patients is still poorly documented. This case report concerns a woman with metastatic lung carcinoma who was sincerely informed and successfully treated with chemotherapy and gefitinib only after gaining the trust of her overprotective daughter. Devoting time to the relatives represents a key element to create a communicative and efficient relationship with older cancer patients. PMID:17036533

  11. Effects of α-Tocopherol and β-Carotene Supplementation on Cancer Incidence and Mortality: 18-Year Post-Intervention Follow-Up of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study

    OpenAIRE

    Virtamo, Jarmo; Taylor, Phil R; Kontto, Jukka; Männistö, Satu; Utriainen, Meri; Weinstein, Stephanie J.; Huttunen, Jussi; Albanes, Demetrius

    2013-01-01

    In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study among 29,133 Finnish male smokers aged 50–69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the post-intervention effects of α-tocopherol and β-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplemen...

  12. Younger women's experiences of deciding against delayed breast reconstruction post-mastectomy following breast cancer: An interpretative phenomenological analysis.

    Science.gov (United States)

    Holland, Fiona; Archer, Stephanie; Montague, Jane

    2016-08-01

    Most women do not reconstruct their breast(s) post-mastectomy. The experiences of younger women who maintain this decision, although important to understand, are largely absent in the research literature. This interview-based study uses interpretative phenomenological analysis to explore the experiences of six women, diagnosed with primary breast cancer in their 30s/40s, who decided against delayed reconstruction. Findings reported here focus on one superordinate theme (decision-making) from a larger analysis, illustrating that the women's drive to survive clearly influenced their initial decision-making process. Their tenacity in maintaining their decision is highlighted, despite non-reconstruction sometimes being presented negatively by medical teams. Patient-centred support recommendations are made. PMID:25516557

  13. Effects of α-Tocopherol and β-Carotene Supplementation on Cancer Incidence and Mortality: 18-Year Post-Intervention Follow-Up of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study

    Science.gov (United States)

    Virtamo, Jarmo; Taylor, Phil R.; Kontto, Jukka; Männistö, Satu; Utriainen, Meri; Weinstein, Stephanie J.; Huttunen, Jussi; Albanes, Demetrius

    2014-01-01

    In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study among 29,133 Finnish male smokers aged 50–69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the post-intervention effects of α-tocopherol and β-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n=2,881) was 1.04 (95% confidence interval [CI], 0.96–1.11) among β-carotene recipients compared with nonrecipients. For prostate cancer (n=2,321) RR was 0.97 (95% CI, 0.89–1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing approximately 8 years post-intervention. Body mass index significantly modified the effect of α-tocopherol on prostate cancer (P for interaction=0.01): RR 1.00 (95% CI, 0.88–1.14) in normal-weight men, 0.87 (95% CI, 0.77–0.98) in overweight men, and 1.25 (95% CI, 1.01–1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98–1.05) for α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99–1.05) for β-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70–0.99), whereas β-carotene increased it (RR, 1.20; 95% CI, 1.01–1.42). In conclusion, supplementation with α-tocopherol and β-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality. PMID:24338499

  14. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.

    Science.gov (United States)

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M; Chen, Maoshan; Findlay, Jock K; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  15. Does Secondary Inflammatory Breast Cancer Represent Post-Surgical Metastatic Disease?

    OpenAIRE

    Salman Hashmi; Ladan Zolfaghari; Levine, Paul H

    2012-01-01

    The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation...

  16. Discovering environmental cancer: Wilhelm Hueper, post-World War II epidemiology, and the vanishing clinician's eye.

    Science.gov (United States)

    Sellers, C

    1997-01-01

    Today, our understanding of and approach to the exogenous causes of cancer are dominated by epidemiological practices that came into widespread use after World War II. This paper examines the forces, considerations, and controversies that shaped postwar risk factor epidemiology in the United States. It is argued that, for all of the new capabilities it brought, this risk factor epidemiology has left us with less of a clinical eye for unrecognized cancer hazards, especially from limited and localized exposures in the work-place. The focus here is on Wilhelm Hueper, author of the first textbook on occupational cancer (1942). Hueper became the foremost spokesman for earlier identification practices centering on occupational exposures. The new epidemiological methods and associated institutions that arose in the 1940s and 1950s bore an unsettled relation to earlier claims and methods that some, Hueper among them, interpreted as a challenge. Hueper's critique of the new epidemiology identified some of its limitations and potentially debilitating consequences that remain with us today. Images p1825-a p1827-a p1829-a PMID:9366640

  17. Post-surgical treatment and rehabilitation of the thyroid cancer patients

    International Nuclear Information System (INIS)

    There are 1232 patients opened on for thyroid cancer (TCP) had been examined after surgical treatment in compare with 55 persons without thyroid gland disorder. Desadaptation of TCP just after surgery had been dell with parathyroid insufficiency, disturbances of VII, IX-XII nervure. Increasing of arterial hypotension, chronic gastritis, myome in women, depressive reaction with decreasing of quality of life had been marked in thyroid cancer patients after 4,5±0,2 of treatment stating. In TCP more frequently suffered from neoplastic diseases of localization. Average parameters' level of pulmonary volume, immunology status, antioxidative activity was lover in TCP then it was in control group. Recurrence of thyroid cancer was deal with type of surgical treatment, TSH- suppression and compliments of TCP. It was revealed that thyroxin suppressive dose is deal from body mass index, higher in men then in women and in patients' group after radiotherapy. Disability of TCP related with postoperative complication and cardio-respiratory system status. These come to decreasing in work participation, mobility and communication. System of rehabilitation of TCP had been provided

  18. Adjuvant radioactive iodine (I131) therapy in patients with papillary thyroid cancer: comparison of ablation outcome post low and high doses of I131

    International Nuclear Information System (INIS)

    Full text of publication follows. Introduction: I131 ablation post total thyroidectomy is a well established adjuvant therapy in patients with papillary thyroid cancer. Many factors can affect ablation outcome including size of remnant thyroid tissue, stage of the disease and given dose of I131. Some authors stated that small doses of I131 can achieve successful complete ablation outcome comparable to high ablative dose. Aim: the aim of the current study is to compare successful complete ablation rate using low I131 ablation dose (30 mCi) versus high dose (100 mCi) post total thyroidectomy in patients with papillary thyroid cancer confined to the thyroid gland. Patients and methods: 129 patients with papillary thyroid cancer confined to the thyroid gland, with no regional lymph nodal or systemic metastases, candidates for I131 ablation therapy post total thyroidectomy, were included in the current study. 61 patients received 30 mCi ablative dose on our patient basis. The remaining 68 patients received high ablation dose (100 mCi). All patients performed follow up I131 whole body scan, neck ultrasound and unsuppressed serum thyroglobulin level (Tg) 6-9 months post I131 therapy. Successful complete ablation was considered in absence of any I131 avid thyroid tissue in the neck, free neck ultrasound and Tg level < 2 ng/ml. Results: successful complete ablation post 30 mCi of I131 was noted in 36 out of 61 patients (59%). On the other hand, this was observed post 100 mCi in 56 out of 68 patients (82.3%), with a statistically significant difference between both groups (p<0.05). Conclusion: in patients with papillary thyroid cancer confined to the thyroid gland, candidates for I131 ablation therapy post total thyroidectomy, high ablation dose of I131 (100 mCi) has significantly higher successful complete ablation rate compared to small I131 dose (30 mCi). (authors)

  19. Malignant fibrous histiocytoma of the urinary bladder as a post-radiation secondary cancer: a case report

    Directory of Open Access Journals (Sweden)

    Nimmanon Thirayost

    2011-11-01

    Full Text Available Abstract Introduction Malignant fibrous histiocytomas have been periodically reported as the primary tumor in various organs including the urinary bladder, and is the second most frequent sarcoma of the urinary tract in adults. This report discusses a case of the well established diagnosis of a malignant fibrous histiocytoma of the bladder occurring as a post-radiation cancer after the treatment of a cervical carcinoma. Our findings support those of many previous studies and make the view of the nature of the disease clearer. Case presentation We report the case of a 54-year-old Thai woman who had been treated with radiation therapy for cervical cancer, who presented to our facility with urinary incontinence. Initially, our patient was diagnosed as having a high-grade urothelial carcinoma. Subsequent radical surgery rendered the final pathological diagnosis, confirmed histologically and immunohistochemically as malignant fibrous histiocytoma, with clinical and pathological staging of T4b N0 M0. Adjuvant chemotherapy was provided for our patient. Conclusions This type of malignancy is very aggressive and easily misdiagnosed due to its rarity. Therefore, in a patient with a prior history of irradiation in the pelvic area, this should be considered as a differential diagnosis to ensure early correct diagnosis and treatment.

  20. Post-surgical use of radioiodine (I-131) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation : A consensus report

    NARCIS (Netherlands)

    Pacini, F; Schlumberger, M; Harmer, C; Berg, GG; Cohen, O; Duntas, L; Jamar, F; Jarzab, B; Limbert, E; Lind, P; Reiners, C; Franco, FS; Smit, J; Wiersinga, W

    2005-01-01

    Objective: To determine, based on published literature and expert clinical experience. current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. Design and methods: A literature review was performed and was then analyzed

  1. Personality Change Pre- to Post- Loss in Spousal Caregivers of Patients with Terminal Lung Cancer

    OpenAIRE

    Hoerger, Michael; Chapman, Benjamin P.; Prigerson, Holly G.; Fagerlin, Angela; Mohile, Supriya G.; Epstein, Ronald M; Lyness, Jeffrey M.; Duberstein, Paul R.

    2014-01-01

    Personality is relatively stable in adulthood but could change in response to life transitions, such as caring for a spouse with a terminal illness. Using a case-control design, spousal caregivers (n=31) of patients with terminal lung cancer completed the NEO-FFI twice, 1.5 years apart, before and after the patient’s death. A demographically-matched sample of community controls (n=93) completed the NEO-FFI on a similar timeframe. Based on research and theory, we hypothesized that bereaved car...

  2. Modified partially wide tangents technique in post-mastectomy radiotherapy for patients with left-sided breast cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qian; CHEN Jia-yi; HU Wei-gang; GUO Xiao-mao

    2010-01-01

    Background The role of internal mammary nodes (IMN) irradiation for breast cancer patients after mastectomy remains controversial. This study aimed to compare different techniques for radiation of the chest wall (CW) and IMN post-mastectomy for left-breast cancer patients in terms of dose homogeneity within planning target volume (PTV) and dose to critical structures.Methods Thirty patients underwent CT simulation, while CW, IMN, left lung, heart and contralateral breast were contoured. Three three-dimensional conformal radiotherapy (3D-CRT) techniques, namely, standard tangents, partially wide tangents (PWT), and modified PWT techniques plus intensity modulated radiotherapy (IMRT) technique have been used to radiate CW and IMN. In addition to the target coverage and dose homogeneity, we also evaluated the dose to the critical structures including heart, left lung and contralateral breast.Results All three 3D-CRT techniques provided satisfactory coverage regarding total PTV. The PWT and the modified PWT gave better coverage of IMN PTV with V47.5 of (96.83±4.56)% and (95.19±3.90)% compared to standard tangents ((88.16±7.77)%), P <0.05. The standard tangents also contributed the biggest IMN VD105%, VD110%, VD115% and VD120%. The lowest mean dose of the heart was achieved by the modified PWT ((8.47±2.30) Gy), compared with PWT ((11.97±3.54)Gy) and standard tangents ((11.18±2.53) Gy). The mean dose of lung and contralateral breast with the modified PWT was significantly lower than those with PWT. Comparing IMRT with the modified PWT, both techniques provided satisfactory coverage. The conformity indexes (CI) with IMRT (CI1: 0.71±0.02; CI2: 0.64±0.02) were better than those with the modified PWT (CI1: 0.50±0.02; CI2: 0.45±0.02). The mean dose, V5, V10 and V5-10 of heart and left lung with the modified PWT were significantly lower than those with the IMRT. The mean dose and VD2% of contralateral breast with the modified PWT were not significantly different

  3. Does Secondary Inflammatory Breast Cancer Represent Post-Surgical Metastatic Disease?

    Energy Technology Data Exchange (ETDEWEB)

    Hashmi, Salman; Zolfaghari, Ladan; Levine, Paul H., E-mail: sphphl@gwumc.edu [Department of Epidemiology and Biostatistics, George Washington University School of Public Services and Health Services, Washington, DC 20037 (United States)

    2012-02-20

    The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC at the traumatized site that have been identified by our IBC Registry (IBCR) and hypothesize that angiogenesis appearing as part of the healing process could act as an accelerant to an otherwise latent breast malignancy. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer.

  4. Does Secondary Inflammatory Breast Cancer Represent Post-Surgical Metastatic Disease?

    Directory of Open Access Journals (Sweden)

    Salman Hashmi

    2012-02-01

    Full Text Available The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC at the traumatized site that have been identified by our IBC Registry (IBCR and hypothesize that angiogenesis appearing as part of the healing process could act as an accelerant to an otherwise latent breast malignancy. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer.

  5. Does Secondary Inflammatory Breast Cancer Represent Post-Surgical Metastatic Disease?

    International Nuclear Information System (INIS)

    The phenomenon of accelerated tumor growth following surgery has been observed repeatedly and merits further study. Inflammatory breast carcinoma (IBC) is widely recognized as an extremely aggressive malignancy characterized by micrometastasis at the time of diagnosis, with one interesting subgroup defined as secondary IBC where pathologically identifiable IBC appears after surgical treatment of a primary non-inflammatory breast cancer. One possible mechanism can be related to the stimulation of dormant micrometastasis through local angiogenesis occurring as part of posttraumatic healing. In this report, we review cases of secondary IBC and others where localized trauma was followed by the appearance of IBC at the traumatized site that have been identified by our IBC Registry (IBCR) and hypothesize that angiogenesis appearing as part of the healing process could act as an accelerant to an otherwise latent breast malignancy. It is therefore possible that secondary IBC can be used as a model to support local angiogenesis as an important contributor to the development of an aggressive cancer

  6. Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance.

    Science.gov (United States)

    Wang, Yuetong; Huang, Hsin-Yi; Yang, Liu; Zhang, Zhanxia; Ji, Hongbin

    2016-01-01

    Drug resistance to tyrosine kinase inhibitor (TKI) is the main obstacle for efficient treatment of epidermal growth factor receptor (EGFR)-mutant lung cancer patients. Here we design a cetuximab-capped mesoporous silica nanoparticle (MP-SiO2 NP) as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded drugs including doxorubicin and gefitinib. This innovative nano-medicine can specifically target lung cancer cells with high EGFR expression rather than those with low EGFR level. Treatment of a gefitinib-resistant cell line derived from PC9 cell (PC9-DR) with the gefitinib-loaded cetuximab-capped MP-SiO2 NP showed a significant inhibition of cell growth. Moreover, this nano-medicine successfully suppressed the progression of PC9-DR xenograft tumors. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione (GSH) level in PC9-DR cells. Collectively, our study provides a novel approach to overcome EGFR-TKI resistance using cetuximab modified MP-SiO2 NP, which holds strong potential for effective management of EGFR-mutant lung cancer. PMID:27151505

  7. Early Post Operative Enteral Versus Parenteral Feeding after Esophageal Cancer Surgery

    Directory of Open Access Journals (Sweden)

    Mohammadtaghi Rajabi Mashhadi

    2015-09-01

    Full Text Available Introduction: The incidence of malnutrition in hospitalized patients is reported to be high. In particular, patients with esophageal cancer are prone to malnutrition, due to preoperative digestive system dysfunctions and short-term non-oral feeding postoperatively. Selection of an appropriate method for feeding in the postoperative period is important in these patients.   Materials and Methods: In this randomized clinical trial, 40 patients with esophageal cancer who had undergone esophagectomy between September 2008 and October 2009 were randomly assigned into either enteral feeding or parenteral feeding groups, with the same calorie intake in each group. The level of serum total protein, albumin, prealbumin, transferrin, C3, C4 and hs-C-reactive protein          (hs-CRP, as well as the rate of surgical complications, restoration of bowel movements and cost was assessed in each group.   Results: Our results showed that there was no significant difference between the groups in terms of serum albumin, prealbumin or transferrin. However, C3 and C4 levels were significantly higher in the enteral feeding group compared with the parenteral group, while hs-CRP level was significantly lower in the enteral feeding group. Bowel movements were restored sooner and costs of treatment were lower in the enteral group. Postoperative complications did not differ significantly between the groups. There was one death in the parenteral group 10 days after surgery due to myocardial infarction.   Conclusion:  The results of our study showed that enteral feeding can be used effectively in the first days after surgery, with few early complications and similar nutritional outcomes compared with the parenteral method. Enteral feeding was associated with reduced inflammation and was associated with an improvement in immunological responses, quicker return of bowel movements, and reduced costs in comparison with parenteral feeding.

  8. Effects of β - sodium aescinate on edema of affected upper limbs in patients post breast cancer operations%β-七叶皂苷钠治疗乳腺癌术后患侧上肢水肿的疗效观

    Institute of Scientific and Technical Information of China (English)

    施怀杰; 王爱玉

    2001-01-01

    @@ Background: Edema has effect on rehabilitation of the patients post breast cancer operations . Objective: The study on effects of β - sodium aescinate on subduing edema and acceleration to regress swell in patients post breast cancer operations was reported.

  9. Uni- and multivariate analysis of eight indications for post-operative radiotherapy and their significance for local-regional cure in advanced head and neck cancer

    International Nuclear Information System (INIS)

    Eighty consecutive patients with advanced head and neck cancer were treated with combined therapy of radical surgery and post-operative radiotherapy. Indications for post-operative radiotherapy were pathological staging of the primary tumour (pT3 or pT4), poorly differentiated or undifferentiated carcinoma (G3, G4), tumour thickness, tumour invasion in the surrounding tissues with slender tumour strands and solitary tumour cells, perineural spread, lymphangio-invasive tumour growth, multiple positive neck nodes or extranodal spread, and microscopical irradicality of the surgical margins. The contribution for prognosis of these indications for post-operative radiotherapy were retrospectively calculated in univariate and multivariate analysis. Of all investigated parameters, the mode of tumour invasion and lymphangio-invasive growth were independent prognostic factors. If these unfavourable prognostic signs are present, post-operative radiotherapy has to be intensified to at least curative doses of 66 Gy or more to areas at risk. (author)

  10. Lymph node ratio predicts the benefit of post-operative radiotherapy in oral cavity cancer

    International Nuclear Information System (INIS)

    Background: The standard treatment for non-metastatic oral cavity squamous cell carcinoma (OCSCC) is surgical resection followed by post-operative radiotherapy (PORT) with/without chemotherapy in high risk patients. Given the substantial toxicity of PORT we assessed lymph node ratio (LNR) as a predictor of PORT benefit. Design: By using the Surveillance, Epidemiology and End Results (SEER) database, we analyzed all node positive OCSCC patients diagnosed between 1988 and 2007 who underwent neck dissection. LNR was categorized into three groups: <6%, 6–12.5% and >12.5%. Results: In 3091 subjects identified, median survival was 32, 25 and 16 months for LNR Groups 1, 2 and 3, respectively. On multivariate analysis, survival was associated with age, race, grade, tumor size, nodal stage, extra-capsular extension, use of PORT and LNR. When stratified by LNR group, PORT was associated with a survival benefit only in Group 3 (LNR > 12.5%): 2 year survival 25% vs 37%. No benefit to PORT was seen when the LNR ⩽ 12.5%: 2 year survival 51% vs 54%. Conclusion: A low LNR is associated with extended survival in LN positive OCSCC. The survival benefit associated with PORT in this disease appears to be limited to those with a LNR > 12.5%. Validation is required prior to the clinical implementation of our findings

  11. A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Pilkington, Gerlinde; Boland, Angela; Brown, Tamara; Oyee, James; Bagust, Adrian; Dickson, Rumona

    2015-04-01

    Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC. PMID:25661113

  12. Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with 90Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent 18F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUVmax) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p 25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using 18F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  13. Melanoma-associated antigen expression and the efficacy of tyrosine kinase inhibitors in head and neck cancer

    DEFF Research Database (Denmark)

    Hartmann, Stefan; Brands, Roman C; Küchler, Nora; Fuchs, Andreas; Linz, Christian; Kübler, Alexander C; Müller-Richter, Urs D A

    2015-01-01

    Melanoma-associated antigen (MAGE) has been identified in a variety of types of cancer. The expression of several MAGE subgroups is correlated with poor prognosis and chemotherapeutic resistance. One target of chemotherapeutic treatment in head and neck cancer is the epidermal growth factor recep...... between MAGE-A5 and -A11 and lower efficacy of EGFR TKIs. Pretreatment analysis of MAGE-A status may therefore aid improvement of chemoprevention using erlotinib and gefitinib in head and neck cancer....

  14. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

    International Nuclear Information System (INIS)

    To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group). The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study. For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome

  15. Preclinical evaluation of 99mTc labeled gefitinib as a potential scintigraphic probe for the detection of tumors expressing epidermal growth factor receptors

    International Nuclear Information System (INIS)

    In the present study, we successfully radiolabeled gefitinib with 99mTc by direct labeling method. The radio-ligand had radiolabeling efficiency of >95.0% and in vitro stability of >80.0% at 24 h. The radiotracer cleared from blood bi-exponentially. Animal organ biodistribution data indicated hepato-renal excretion of the radiotracer. Scintigraphy carried out in tumor bearing mice (induced by EGFR expressing EAT cell lines) demonstrated that the radiotracer accumulated in the tumor site with T/NT ratio of 3.3±0.2 at 1 h. - Highlights: • Gefitinib – an epidermal growth factor receptor inhibitor was successfully radiolabeled with 99mTc and the resultant radiolabel 99mTc-gefitinib had high radiolabeling efficiency and in vitro stability. • The radiotracer cleared from blood bi-exponentially. • Animal organ biodistribution data demonstrated hepato-renal excretion of the radiotracer. • Gamma camera imaging in tumor bearing mice demonstrated that the radiotracer accumulated in the tumor site with high target to non target ratio. • The diagnostic efficacy of 99mTc-gefitinib needs clinical validation in tumors expressing high EGFR density

  16. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore); Zhu Congju; Wong Yinling; Gao Qiuhan; Ty, Albert; Wong, Meng Cheong [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore)

    2012-05-01

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are

  17. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    International Nuclear Information System (INIS)

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)–Akt-DNA–dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H2AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H2AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G2/M arrest and increased γ-H2AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H2AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G2/M

  18. Cancer-specific survival after radical nephroureterectomy for upper urinary tract urothelial carcinoma: proposal and multi-institutional validation of a post-operative nomogram

    OpenAIRE

    Yates, D R; Hupertan, V.; Colin, P.; Ouzzane, A; Descazeaud, A; Long, J. A.; Pignot, G; Crouzet, S; Rozet, F; Neuzillet, Y; Soulie, M.; Bodin, T; Valeri, A.; Cussenot, O; Rouprêt, M

    2012-01-01

    Background: Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU. Patients and methods: Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nom...

  19. Responses to concurrent radiotherapy and hormone-therapy and outcome for large breast cancers in post-menopausal women

    International Nuclear Information System (INIS)

    Introduction: This study aimed to evaluate responses and outcome of hormone-therapy (HT) and radiotherapy (RT) given concurrently for large breast cancers in post-menopausal women. Material and methods: Forty-two breast carcinomas in 41 women were treated with HT and concurrent RT to the breast ± lymph node bearing areas. For 30 tumours this was followed by breast surgery (with axillary lymph node dissection when the axilla had not been irradiated). RT delivered a median dose to the tumour of 50 Gy (48-66) and 75 Gy (65-84) for, respectively, preoperative and exclusive RT-HT. Median follow-up was 64 months. Results: Out of 42 clinically assessable tumours (after a mean dose of 50 Gy), 9 tumours (21%) had complete clinical responses, 24 (57%) partial responses, 9 (21%) stable disease. Breast-conserving surgery or exclusive RT-HT was possible in 74% of tumours. For 29 patients who underwent breast surgery, the rate of pathological complete responses was 17%. At 50 Gy no skin toxicity higher than grade 2 occurred. Five year OS, RFS and local control were, respectively, 85%, 84% and 97%. Lymphoedema occurred in one patient. Conclusion: Concurrent association of RT-HT demonstrated good efficacy, both in terms of clinical and pathological complete responses. It allowed breast conservation with acceptable tolerance and good 5-year local control

  20. Objective assessment of dermatitis following post-operative radiotherapy in patients with breast cancer treated with breast-conserving treatment

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken; Takenaka, Tadashi; Tanaka, Eiichi; Kuriyama, Keiko; Yoshida, Mineo [National Hospital Organization Osaka National Hospital (Japan). Dept. of Radiology; Yamazaki, Hideya; Nishimura, Tsunehiko [Kyoto Prefectural Univ. of Medicine (Japan). Dept. of Radiology; Kotsuma, Tadayuki [Osaka Univ. Graduate School of Medicine (Japan). Dept. of Radiation Oncology; Fujita, Yuka [Osaka Univ. Graduate School of Medicine (Japan). Dept. of Diagnostic and Interventional Radiology; Masuda, Norikazu [National Hospital Organization Osaka National Hospital (Japan). Dept. of Surgery

    2010-11-15

    To evaluate radiation dermatitis objectively in patients with breast cancer who had undergone post-operative radiotherapy after breast-conserving surgery. Skin color (L{sup *}, a{sup *}, and b{sup *} values) and moisture analyses were performed for both breasts (before, after, 1 month, 6 months, and 1 year after radiotherapy) to examine irradiated and non-irradiated skin divided into four quadrants in 118 patients. These patients underwent breast conservative surgery followed by 50 Gy/25 fractions (median) of radiotherapy with or without boost irradiation (10 Gy/5 fractions). L{sup *}, a{sup *}, and moisture values were changed by irradiation and maximized at completion or 1 month after radiotherapy. One year after radiotherapy, the skin color had returned to the range observed prior to radiotherapy. However, moisture did not return to previous values even 1 year after treatment. The lateral upper side (quadrant C) showed greater changes than other quadrants in the L{sup *} value (darker) at the end of radiotherapy. The Common Toxicity Criteria version 3 scores were found to correlate well with a{sup *} and L{sup *} values at the completion and 1 month after radiotherapy. Boost radiotherapy intensified reddish and darker color changes at the completion of radiotherapy, while chemotherapy did not intensify the skin reaction caused by radiotherapy. Moisture impairment as a result of irradiation lasts longer than color alterations. Objective assessments are useful for analyzing radiation dermatitis. (orig.)

  1. Racial and ethnic differences in personal cervical cancer screening amongst post-graduate physicians: Results from a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Ross Joseph S

    2008-10-01

    Full Text Available Abstract Background Racial and ethnic disparities in cervical cancer screening have been attributed to socioeconomic, insurance, and cultural differences. Our objective was to explore racial and ethnic differences in adherence to cervical cancer screening recommendations among female post-graduate physicians. Methods We conducted a cross-sectional survey at one university hospital among a convenience sample of 204 female post-graduate physicians (52% of all potential participants, examining adherence to United States Preventive Services Task Force cervical cancer screening recommendations, perception of adherence to recommendations, and barriers to obtaining care. Results Overall, 83% of women were adherent to screening recommendations and 84% accurately perceived adherence or non-adherence. Women who self-identified as Asian were significantly less adherent when compared with women who self-identified as white (69% vs. 87%; Relative Risk [RR] = 0.79, 95% Confidence Interval [CI], 0.64–0.97; P Conclusion Among a small group of insured, highly-educated physicians who have access to health care, we found racial and ethnic differences in adherence to cervical cancer screening recommendations, suggesting that culture may play a role in cervical cancer screening.

  2. Inhibition of the epidermal growth factor receptor in bladder cancer cells treated with the DNA-damaging drug etoposide markedly increases apoptosis

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Nexo, Ebba;

    2007-01-01

    : These results suggest that activation of the EGFR induced a cell-survival function when bladder cancer cells were treated with the DNA-damaging drug VP16, and that combined treatment with VP16 and the EGFR inhibitor gefitinib might improve the efficacy of treatment. Udgivelsesdato: 2007-Jan...

  3. Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore.

    Science.gov (United States)

    Gago-Dominguez, Manuela; Castelao, J Esteban; Sun, Can-Lan; Van Den Berg, David; Koh, Woon-Puay; Lee, Hin-Peng; Yu, Mimi C

    2004-11-01

    We have previously found marine n-3 fatty acids to be inversely related to post-menopausal breast cancer in Chinese women from Singapore. Post-menopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87]. Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is a suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial by-products. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis, nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71, 95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1 positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer relationships were observed in either pre-menopausal or post-menopausal women at baseline. However, post-menopausal women possessing the combined GSTM1 null and GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar

  4. The Health Deviation of Post-Breast Cancer Lymphedema: Symptom Assessment and Impact on Self-Care Agency

    OpenAIRE

    Armer, Jane M.; Henggeler, Mary H; Brooks, Constance W.; Zagar, Eris A.; Homan, Sherri; Bob R. Stewart

    2008-01-01

    Breast cancer is the leading cancer among women world-wide, affecting 1 of 8 women during their lifetimes. In the US alone, some 2 million breast cancer survivors comprise 20% of all cancer survivors. Conservatively, it is estimated that some 20-40% of all breast cancer survivors will develop the health deviation of lymphedema or treatment-related limb swelling over their lifetimes. This chronic accumulation of protein-rich fluid predisposes to infection, leads to difficulties in fitting clot...

  5. Design and process evaluation of an informative website tailored to breast cancer survivors’ and intimate partners’ post-treatment care needs

    OpenAIRE

    Pauwels Evelyn; Van Hoof Elke; Charlier Caroline; Lechner Lilian; de Bourdeaudhuij Ilse

    2012-01-01

    Abstract Background On-line provision of information during the transition phase after treatment carries great promise in meeting shortcomings in post-treatment care for breast cancer survivors and their partners. The objectives of this study are to describe the development and process evaluation of a tailored informative website and to assess which characteristics of survivors and partners, participating in the feasibility study, are related to visiting the website. Methods The development p...

  6. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

    OpenAIRE

    Kim, Choung-Soo; Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-01-01

    Purpose This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-...

  7. Using a mass media campaign to raise women's awareness of the link between alcohol and cancer: cross-sectional pre-intervention and post-intervention evaluation surveys

    OpenAIRE

    Dixon, Helen G; Pratt, Iain S; Scully, Maree L; Miller, Jessica R; Patterson, Carla; Hood, Rebecca; Slevin, Terry J

    2015-01-01

    Objectives To evaluate the effectiveness of a population-based, statewide public health intervention designed to improve women's awareness and knowledge of the link between alcohol and cancer. Design Cross-sectional tracking surveys conducted pre-intervention and post-intervention (waves I and III of campaign). Setting Western Australia. Participants Cross-sectional samples of Western Australian women aged 25–54 years before the campaign (n=136) and immediately after wave I (n=206) and wave I...

  8. The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer

    OpenAIRE

    Spych, Michał; Gottwald, Leszek; Klonowicz, Małgorzata; Biegała, Michał; Bibik, Robert; Fijuth, Jacek

    2010-01-01

    Introduction The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. Material and methods The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated...

  9. EGFR: The Paradigm of an Oncogene-Driven Lung Cancer

    OpenAIRE

    Riely, Gregory J.; Yu, Helena A.

    2015-01-01

    Somatic, activating mutations in Epidermal Growth Factor Receptor (EGFR) identify a significant minority of patients with non-small cell lung cancer (NSCLC). While these mutations are associated with an ~70% response rate to some EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, and afatinib), patients develop resistance (i.e. “acquired resistance”) after a median of 9–12 months. In patients with clinical acquired resistance, repeat biopsy of tumors has identified a number of relevant me...

  10. Neoadjuvant hormonal therapy is associated with comparable outcomes to neoadjuvant chemotherapy in post-menopausal women with estrogen receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    David M. Marcus

    2013-12-01

    Full Text Available Objectives: We compared outcomes in post-menopausal estrogen receptor-positive (ER+ breast cancer patients treated with neoadjuvant hormonal therapy (NAHT or neoadjuvant chemotherapy (NACT.Methods: We retrospectively identified post-menopausal women who received either NAHT or NACT for non-metastatic, non-inflammatory, ER+, Her2neu negative breast cancer from 2004 to 2011. We compared long-term rates of locoregional relapse free survival (LRFS, distant metastasis free survival (DMFS, and overall survival (OS using the Kaplan-Meier method. The Cox proportional hazards model was used to identify patient and disease factors significantly associated with these endpoints. Results: We identified 99 patients in our study, including 27 who received NAHT and 72 who received NACT. There were no differences in 4-year LRFS, DMFS, or OS between groups. On Cox proportional hazards modeling, the type of systemic therapy (NAHT vs. NACT was not associated with OS. However, patients with progesterone receptor (PR positive disease had a 92% lower risk of death compared to patients with PR negative disease.Conclusions: Our data suggest that outcomes are not adversely affected by NAHT in post-menopausal women with ER+ breast cancer. Therefore, NAHT is a viable and potentially less toxic option than NACT in appropriately selected patients. Furthermore, although PR negative disease appears to be associated with poor prognosis, intensification of systemic treatment with chemotherapy may not be associated with improvement of disease-related outcomes in this patient population.

  11. Post-mastectomy radiotherapy in Denmark: From 2D to 3D treatment planning guidelines of The Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Thomsen, Mette Skovhus; Berg, Martin; Nielsen, Hanne M.;

    2008-01-01

    , it was investigated whether it was possible to find a treatment technique alternative to the one recommended by the Danish Breast Cancer Cooperative Group (DBCG). A dosimetric comparison of a combined photon/electron 3-field technique (3F) and a partial wide tangent technique (PWT) was carried out on individual......This paper describes the procedure of changing from 2D to 3D treatment planning guidelines for post-mastectomy radiotherapy in Denmark. The aim of introducing 3D planning for post-mastectomy radiotherapy was to optimize the target coverage and minimize the dose to the normal tissues. Initially...... to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy...

  12. Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space

    Directory of Open Access Journals (Sweden)

    Sartor A Oliver

    2011-04-01

    Full Text Available Abstract Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC. Despite this designation, however, there is evidence that androgen receptor (AR-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 demonstrated that docetaxel chemotherapy could significantly improve survival. These results established first-line docetaxel as the standard of care for mCRPC. After resistance to further docetaxel therapy develops, treatment options were once again limited. Recently reported results from phase 3 trials have shown that additional therapy with the novel taxane cabazitaxel (with prednisone, or treatment with the antiandrogen abiraterone (with prednisone could improve survival for patients with mCRPC following docetaxel therapy. Compared with mitoxantrone/prednisone, cabazitaxel/prednisone significantly improved overall survival, with a 30% reduction in rate of death, in patients with progression of mCRPC after docetaxel therapy in the TROPIC trial. Similarly, abiraterone acetate (an inhibitor of androgen biosynthesis plus prednisone significantly decreased the rate of death by 35% compared with placebo plus prednisone in mCRPC patients progressing after prior docetaxel therapy in the COU-AA-301 trial. Results of these trials have thus established two additional treatment options for mCRPC patients in the "post-docetaxel space." In view of the continued AR

  13. MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer

    International Nuclear Information System (INIS)

    LATS2 is a member of the LATS tumor suppressor family. It has been implicated in regulation of the cell cycle and apoptosis. Frequent loss of heterozygosity (LOH) of LATS2 has been reported in human esophageal cancer. But, the LATS2 gene expression and its regulatory mechanism in esophageal cancer remain unclear. The present study has shown that LATS2 protein expression was mediated by miR-373 at the post-transcriptional level and inversely correlated with miR-373 amounts in esophageal cancer cell lines. Furthermore, we demonstrated that the direct inhibition of LATS2 protein was mediated by miR-373 and manipulated the expression of miR-373 to affect esophageal cancer cells growth. Moreover, this correlation was supported by data collected ex vivo, in which esophageal cancer tissues from esophageal squamous cell carcinoma (ESCC) patients were analyzed. Finally, by miRNA microarray analysis, four miRNAs including miR-373 were over-expressed in ESCC samples. Our findings reveal that miR-373 would be a potential oncogene and it participates in the carcinogenesis of human esophageal cancer by suppressing LATS2 expression.

  14. TRANSVERSUS ABDOMINIS PLANE BLOCK : A COMPLEMENTARY TECHNIQUE FOR POST OPERATIVE ANALGESIA IN LOWER ABDOMINAL GYNECOLOGICAL CANCER SURGERIES

    Directory of Open Access Journals (Sweden)

    Arathi

    2015-06-01

    Full Text Available BACKGROUND : Gynecological cancer surgeries differ from non - cancer surgeries as the former involves extensive dissection , and tissue handling , which contributes to increased nociception perioperatively. Radical hysterectomy with pelvic lymph node dissection is one of the most commonly performed surgeries in gynecological oncological set up. Transversus abdominis plane (TAP block is one of the new promising regional anesthesia technique complementing multi modal analgesic regimen. This is a prospective randomized controlled trial. We evaluated the role of the TAP block in Radical hysterectomy with pelvic lymph node dissection for periope rative analgesia and reducing the requirement of opioid consumption . METHODS : 100 patients of ASA grade 1 and 2 undergoing radical hysterectomy and pelvic lymph node dissection with below umbilical incision were randomized as block group to undergo TAP blo ck with bupivacaine 0.25% 20ml on each side (n=50 , versus non - block group (n=50. All patients received general anesthethesia. Block was performed before surgical incision bilaterally by using blind double pop technique in patients who were randomized to the block group. Intra operative analgesic regimen was with inj fentanyl 1.5 mic/k.g , repeated with 0.5mic/k.g depending on the requirement as assessed by the anaesthe - siologist based on haemodynamic parameters and post operatively by pain scores on numeri c visual analogue scale with inj . paracetamol 1gm followed by tramadol 2mg/kg and fentany 0.5mic/kg . Each patient was assessed post operatively at 0 , 2 , 4 , 6 , 8 , 12 , 16 , 20 , 24 hours for pain , nausea , vomiting and sedation . The data recorded . Descriptive a nd inferential sta ti stical analysis has been carried out using student t test , chi square/ fisher exact test in the present study. RESULTS : We studied 100 patients , 50 patients in block group and 50 patients in non - block group. The block group had significantly less pain

  15. POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage IIIA, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of M1 need to be further studied.

  16. Gastrin-Releasing Peptide Receptor Mediates Activation of the Epidermal Growth Factor Receptor in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sufi Mary Thomas

    2005-04-01

    Full Text Available Gastrin-releasing peptide receptor (GRPR and the epidermal growth factor receptor (EGFR are expressed in several cancers including non-small cell lung carcinoma (NSCLC. Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP, in NSCLC cells. GRP induced rapid activation of p44/42 MAPK in lung cancer cells through EGFR. GRP-mediated activation of MAPK in NSCLC cells was abrogated by pretreatment with the anti-EGFR-neutralizing antibody, C225. Pretreatment of NSCLC cells with neutralizing antibodies to the EGFR ligands, TGF-α or HB-EGF, also decreased GRP-mediated MAPK activation. On matrix metalloproteinase (MMP inhibition, GRP failed to activate MAPK in NSCLC cells. EGF and GRP both stimulated NSCLC proliferation, and inhibition of either EGFR or GRPR resulted in cell death. Combining a GRPR antagonist with the EGFR tyrosine kinase inhibitor, gefitinib, resulted in additive cytotoxic effects. Additive effects were seen at gefitinib concentrations from 1 to 18μM, encompassing the ID50 values of both gefitinib-sensitive and gefitinib-resistant NSCLC cell lines. Because a major effect of GRPR appears to be promoting the release of EGFR ligand, this study suggests that a greater inhibition of cell proliferation may occur by abrogating EGFR ligand release in consort with inhibition of EGFR.

  17. Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspa- se-3-mediated Apoptosis Induction

    Directory of Open Access Journals (Sweden)

    Sikdar Sourav

    2013-09-01

    Full Text Available Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP in white rats (Rattus norvegicus. Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one (5th, two (5th-6th and three (5th-7th months, respectively, and were sacrificed at the corresponding time- points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM, annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR, immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two- month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR expression, a

  18. The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations

    OpenAIRE

    Okamoto, Isamu; Mitsudomi, Tetsuya; Nakagawa, Kazuhiko; Fukuoka, Masahiro

    2010-01-01

    Gefitinib and erlotinib, small-molecule tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), were the first molecularly targeted agents to become clinically available for the treatment of non-small cell lung cancer (NSCLC). During the course of their clinical development, it has become clear that the substantial clinical benefit associated with EGFR-TKIs is limited ...

  19. Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Whoon Jong; Nichols, Romaine C. Jr. [Dept. of Radiation Oncology, Univ. of Florida, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: rnichols@floridaproton.org; And others

    2013-04-15

    Background: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. Material and methods: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. Results: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. Conclusion: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.

  20. A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province

    Directory of Open Access Journals (Sweden)

    Bryant Heather E

    2004-04-01

    Full Text Available Abstract Background Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. Methods In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. Results A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P Conclusions The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

  1. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib

    OpenAIRE

    Bean, James; Brennan, Cameron; Shih, Jin-Yuan; Riely, Gregory,; Viale, Agnes; Wang, Lu; Chitale, Dhananjay; Motoi, Noriko; Szoke, Janos; Broderick, Stephen; Balak, Marissa; Chang, Wen-Cheng; Yu, Chong-Jen; Gazdar, Adi; Pass, Harvey

    2007-01-01

    In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with t...

  2. Post-GWAS gene–environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women

    OpenAIRE

    Barrdahl, Myrto; Canzian, Federico; Joshi, Amit D.; Ruth C Travis; Chang-Claude, Jenny; Auer, Paul L.; Gapstur, Susan M.; Gaudet, Mia; Diver, W Ryan; Brian E Henderson; Haiman, Christopher A.; Fredrick R Schumacher; Le Marchand, Loïc; Berg, Christine D; Chanock, Stephen J.

    2014-01-01

    We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case–control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC...

  3. Effect of Tai Chi Chuan on serotonin and cortisol for monitoring stress and quality of life in post-treatment breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    William Wai Nam Tsang; Wings Tjing Yung Loo; Louis Wing Cheong Chow; Elizabeth Lam Yan Ng; Adrian Yun San Yip; Jianping Chen

    2014-01-01

    Objective Immediate physical exercise has been recommended for patients in the recovery phase to improve survival and quality of life ( QOL ) and reduce recurrence of disease .The new NCCN Guidelines for Survivorship also highlighted the role of exercise in post -cancer health , encouraging patients to perform light physical activity following treatment .The aim of our study is to effect of Tai Chi Chuan ( TCC) on serotonin and cortisol for monitoring stress and QOL in post-treatment breast cancer patients .Methods Totally 85 post-treatment breast cancer patients were enrolled in this study to observe the effects of practicing TCC on recovery , as well as stress and happiness which are indicators of QOL of in patients .Peripheral blood was drawn from study subjects to analyze the levels of serotonin , cortisol and high sensitive C-reactive protein ( HS-CRP) at baseline, and at 3, 6 and 12 months of TCC practice .Blood was drawn from healthy subjects only at baseline . A QOL questionnaire was administered to study subjects at three time points throughout the study , and once for healthy controls.The data were processed by analysis of variance of repeated measurement .Results At 3, 6 and 12 months time points following regular TCC exercise , WBC, RBC, hemoglobin in blood samples showed a statistically significant difference ( F=161.55 , 172.14 , 289.73; all P=0.00 ) ; the level of serotonin (biomarker for well-being), cortisol (indicator of stress) and HS-CRP (biomarker for inflammation) showed a statistical improvement (F=307.46, 182.85, 102.23; all P=0.00).After 3, 6 and 12 months of regular TCC exercise, according to the results of QOL questionnaire , the indicators including quality of sleep , perceived hunger, fatigue, contentment, stress and social interaction presented a significant difference (F=312.98 , 222.64 , 543.90 ,46.05 ,28.10 ,78.92 , all P<0.05 ) , while there was no statistical difference in life dissatisfaction ( F=56.61 , P=0 .166 ) Conclusions

  4. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer

    OpenAIRE

    Jin Sheng; Wenfeng Fang; Juan Yu; Nan Chen; Jianhua Zhan; Yuxiang Ma; Yunpeng Yang; Yanhuang; Hongyun Zhao; Li Zhang

    2016-01-01

    The effects of treatments to programmed death ligand-1 (PD-L1) expression is unknown. The aim of this study was to investigate the impact of neoadjuvant chemotherapy (NACT) on PD-L1 expression in non-small cell lung cancer (NSCLC) patients. PD-L1 expression was detected by immunohistochemistry (IHC) method in 32 paired tumor specimens pre and post-NACT. The positivity of PD-L1 on tumor cells (TCs) changed from 75% to 37.5% after NACT (p = 0.003). Cases with IHC score of 1, 2, 3 all underwent ...

  5. Comparison of diagnostic and post-theraphy radioiodine scan in well-differentiated thyroid cancer and the clinical outcome

    International Nuclear Information System (INIS)

    We compared the first postoperative diagnostic and post-therapy scans of patients who received therapeutic doses of I-131, to investigate the difference in clinical outcomes between patients with concordant findings of diagnostic and post-therapy scans and patients with discrepant (more lesions in post-therapy scan) findings. The first postoperative diagnostic and post-therapy radioiodine scans of the hundred forty three patients with well differentiated thyroid carcinoma were reviewed. Diagnostic scans were obtained following ingestion of 185 MBq of I-131 and post-therapy scans were obtained after therapeutic dose of 3.7-9.3 GBq of I-131. Successful ablation was defined as no radioiodine uptake on diagnostic radioiodine scan and normal range of serum thyroglobulin level (<10ng/ml) during serum TSH elevation. Discrepant scan findings were noted in 25 (17.5%) patients. Twenty-two patients (15.4%) showed more lesions in post-therapy scan and 3 patients (2.1%) showed stunning effect. Nine (64.3%) of 14 patients with distant metastasis revealed metastatic lesion(s) only on post-therapy scan. Stunning effect was considered as sublethal damage in 1 patient and treatment by a diagnostic dose in 2 patients. Ablation was achieved in 52.4% (75/43) of all patients. Ablation rate and mean cumulative radioiodine dose were not different statistically between concordant and discrepant groups. There were 17.5% difference between diagnostic and post-therapy scan findings when using 185 MBq of I-131 as a diagnostic dose. However, 64.3% of distant metastases were revealed only on post-therapy scan. Ablation rate and mean cumulative radioiodine dose were not different statistically between concordant and discrepant groups. The stunning effect was considered as not only sublethal damage but also treatment by a small diagnostic dose of radioiodine.=20

  6. A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members

    Directory of Open Access Journals (Sweden)

    Dawson Jeremy

    2010-06-01

    Full Text Available Abstract Background The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. Methods The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59% team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Results Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Conclusions Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on

  7. Result of salvage radiotherapy for post-operative PSA failure of prostate cancer. Evaluation of predictive factors

    International Nuclear Information System (INIS)

    Fifty-five patients with prostate specific antigen (PSA) failure were treated with salvage radiotherapy. Post-operative and post-radiotherapy PSA failure was defined as the PSA elevation (nadir +0.2 ng/ml) or the initiation of hormone therapy. The median follow-up period after salvage radiotherapy was 32 months (range; 1-67 months). The 3-yrs biochemical free survival and overall survival rate was 66.7% and 100%. Result of salvage radiotherapy for post-operation PSA failure is good and only the dose was significant predictive factor (60 Gy vs > 64 Gy; 53.9% vs 86.2%). (author)

  8. A Multi-stage Carcinogenesis Model to Investigate Caloric Restriction as a Potential Tool for Post-irradiation Mitigation of Cancer Risk

    Science.gov (United States)

    Tani, Shusuke; Blyth, Benjamin John; Shang, Yi; Morioka, Takamitsu; Kakinuma, Shizuko; Shimada, Yoshiya

    2016-01-01

    The risk of radiation-induced cancer adds to anxiety in low-dose exposed populations. Safe and effective lifestyle changes which can help mitigate excess cancer risk might provide exposed individuals the opportunity to pro-actively reduce their cancer risk, and improve mental health and well-being. Here, we applied a mathematical multi-stage carcinogenesis model to the mouse lifespan data using adult-onset caloric restriction following irradiation in early life. We re-evaluated autopsy records with a veterinary pathologist to determine which tumors were the probable causes of death in order to calculate age-specific mortality. The model revealed that in both irradiated and unirradiated mice, caloric restriction reduced the age-specific mortality of all solid tumors and hepatocellular carcinomas across most of the lifespan, with the mortality rate dependent more on age owing to an increase in the number of predicted rate-limiting steps. Conversely, irradiation did not significantly alter the number of steps, but did increase the overall transition rate between the steps. We show that the extent of the protective effect of caloric restriction is independent of the induction of cancer from radiation exposure, and discuss future avenues of research to explore the utility of caloric restriction as an example of a potential post-irradiation mitigation strategy. PMID:27390741

  9. Studies on the prediction of post-treatment pulmonary functions in lung cancer patients undergoing carbon radiotherapy, during which the first bronchi was included within the radiation field

    International Nuclear Information System (INIS)

    In cases of cancer that have developed at the site peripheral to the segmental bronchus, if the cancer tumor exists near the hilar area and if a dose of more than 95% is irradiated on the proximal portion of the segmental bronchus rather than on its inlet, stenosis or obstruction may occur in the central airway where there is no cancer infiltration. In such cases, it is expected that pulmonary functions may be lost to the same degree as cases in which lobectomy is performed; hence, patients with a poor pulmonary function may suffer from serious disorders. We studied these cases to determine whether it is possible to predict the post-treatment pulmonary functions prior to treatment. The dose to be irradiated on the first bronchi, cancer infiltration into which was not clarified, was set at a dose of 75% to be irradiated on the tumor. It is simple to predict values of pulmonary function from the proportion of the number of subsegmental branches, but a tendency was observed to underestimate values for vital capacity and overestimate values for FEV1.0. It is believed that the presence of underlying diseases, such as emphysema and asthma, may cause a gap between predicted and measured values. (author)

  10. Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall

  11. Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, Daniel J., E-mail: dkrauss@beaumont.edu [Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan (United States); Hu, Chen [NRG Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, Quebec (Canada); Souhami, Luis [McGill University, Montreal, Quebec (Canada); Gore, Elizabeth M. [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Chafe, Susan Maria Jacinta [Cross Cancer Institute, Edmonton, Alberta (Canada); Leibenhaut, Mark H. [Sutter General Hospital, Sacramento, California (United States); Narayan, Samir [Michigan Cancer Research Consortium CCOP (United States); Torres-Roca, Javier [H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Michalski, Jeff [Washington University, St. Louis, Missouri (United States); Zeitzer, Kenneth L. [Albert Einstein Medical Center, Bronx, New York, New York (United States); Donavanik, Viroon [Christiana Care Health Services Inc CCOP, Newark, Delaware (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, California (United States); McGowan, David G. [Cross Cancer Institute, Edmonton, Alberta (Canada); Jones, Christopher U. [Sutter General Hospital, Sacramento, California (United States); Shipley, William U. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2015-07-15

    Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall

  12. Dosimetric results in implant and post-implant and low rate in brachytherapy prostate cancer with loose seeds and attached

    International Nuclear Information System (INIS)

    The objective is determine differences dosimetry statistics on the dosimetry of the implant and post-implant in brachytherapy of low rate with implants permanent in prostate using seed of 125-I loose and attached Both in lives and in the post-prostatic plans dosimetric coverage is good and restrictions in urethra and rectum for both groups of patients are met. Not migrating with joined is evident, as well as better dosimetric homogeneity. (Author)

  13. Survey of post-gamma-ray colony-forming ability, DNA metabolism and oncogene status in non-malignant fibroblast strains from cancer-prone families and individual cancer patients

    International Nuclear Information System (INIS)

    The in vitro radiobiological studies described here have focused on highly selected individuals comprising some of the most likely cases of predisposition to radiogenic cancer ascertained to date. Our results argue against the existence, within the general population, of quantitatively significant subgroups sensitive to the carcinogenic effects of ubiquitous low-level radiation. In fact, of the forty-six cancer-susceptible conditions examined, only four (i.e. members of the cancer-prone lineage in two kindreds and two isolated patients), exhibited abnormal cellular response to γ-rays in vitro. These findings indicate that in this unprecedented collection of high cancer risk conditions, the incidence of abnormal radiation cytotoxicity is only about two-fold above that found in a randomly selected group of age-matched healthy subjects (i.e, about 9% [4/46 conditions] versus about 5% [1/21 volunteers]). This interpretation of the data assumes, however, that the post-γ-ray CFA assay performed on cultured dermal fibroblasts is a reliable and sensitive indicator of the donor's susceptibility to develop radiogenic cancer, irrespective of the anatomical site or histological type of the tumour(s). (author)

  14. Incidence of thyroid cancer among children of the Ukraine in 1996 as compared to previous post-Chernobyl years

    International Nuclear Information System (INIS)

    In 1996 a high incidence rate of thyroid cancer has persisted in Ukraine among children aged under 15 years, which averaged, according to preliminary data, 0.44 case per 100 thousand children's population. The geographical distribution of thyroid cancer cases in children of Ukraine is mainly related, as in previous years, with the most affected regions following the Chernobyl accident. The highest incidence of thyroid cancer (over 80%) was observed in those patients who were aged under 5 years at the moment of the accident, being the most radiosensitive age group. Among thyroid tumors removed in 1996, as in previous years, papillary carcinomas prevail, which are characterized by marked invasive properties. (author)

  15. Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy

    Directory of Open Access Journals (Sweden)

    Adriaenssens Nele

    2012-05-01

    Full Text Available Abstract Background Scapula alata (SA is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT. Methods The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. Results Of 119 evaluable patients, 13 (= 10.9% had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009, 6.1 (P = 0.016, and 6.1 (P = 0.005, respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% (P = 0.036 and abduction decreased by 8.6% (P = 0.046 among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. Conclusion The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.

  16. Which biomarker predicts benefit from EGFR-TKI treatment for patients with lung cancer?

    OpenAIRE

    Uramoto, H; Mitsudomi, T.

    2007-01-01

    Subsets of patients with non-small cell lung cancer respond remarkably well to small molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptor (EGFR) such as gefitinib or erlotinib. In 2004, it was found that EGFR mutations occurring in the kinase domain are strongly associated with EGFR-TKI sensitivity. However, subsequent studies revealed that this relationship was not perfect and various predictive markers have been reported. These include EGFR gene copy numbe...

  17. Review of the current targeted therapies for non-small-cell lung cancer

    OpenAIRE

    Nguyen, Kim-Son H.; Neal, Joel W.; Wakelee, Heather

    2014-01-01

    The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review...

  18. Management of breast cancer in an Asian man with post-traumatic stress disorder: a case report

    OpenAIRE

    Patel, Faaizah; Achuthan, Rajgopal; Hyklova, Lucie; Hanby, Andrew M.; Speirs, Valerie

    2016-01-01

    Background Migration to the UK has increased considerably, which is reflected in the diverse multicultural population which includes asylum seekers and economic migrants. Differences in ethnic and cultural values between the host and newcomer populations could impact on effective health care provision, especially in gender-biased conditions such as breast cancer. Breast cancer is rare in men and the diagnosis is often met with disbelief. This case report describes an unusual case of breast ca...

  19. Orofacial rehabilitation of patients with post-cancer treatment-An overview and report of three cases

    OpenAIRE

    K S Guttal; V G Naikmasur; C B Rao; R K Nadiger; S S Guttal

    2010-01-01

    According to World Health Organisation statistics, individuals of the Indian subcontinent have the highest prevalence of orofacial cancer. Surgery, radiation, chemotherapy or combination therapies are commonly administered treatment modalities for treatment of oral cancer. Surgical resection can be mutilating, disfiguring and may deeply affect self-image of patients. Orofacial defects have unique limitations and challenges. A coordinated effort from the surgeon, oral physician and the maxillo...

  20. Sodium borocaptate (BSH) for Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model: boron biodistribution at 9 post administration time-points

    International Nuclear Information System (INIS)

    The therapeutic success of Boron Neutron Capture Therapy (BNCT) depends centrally on boron concentration in tumor and healthy tissue. We previously demonstrated the therapeutic efficacy of boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) as boron carriers for BNCT in the hamster cheek pouch oral cancer model. Given the clinical relevance of sodium mercaptoundecahydro-closo-dodecaborate (BSH) as a boron carrier, the aim of the present study was to expand the ongoing BSH biodistribution studies in the hamster cheek pouch oral cancer model. In particular, we studied 3 additional post-administration time-points and increased the sample size corresponding to the time-points evaluated previously, to select more accurately the post-administration time at which neutron irradiation would potentially confer the greatest therapeutic advantage. BSH was dissolved in saline solution in anaerobic conditions to avoid the formation of the dimer BSSB and its oxides which are toxic. The solution was injected intravenously at a dose of 50 mg 10 B/kg (88 mg BSH / kg). Different groups of animals were killed humanely at 7, 8, and 10 h after administration of BSH. The sample size corresponding to the time-points 3, 4, 6, 9 and 12 h was increased. Samples of blood, tumor, precancerous tissue, normal pouch tissue, cheek mucosa, parotid gland, palate, skin, tongue, spinal cord marrow, brain, liver, kidney, spleen and lung were processed for boron measurement by Optic Emission Spectroscopy (ICP-OES). Boron concentration in tumor peaked to 24-34 ppm, 3-10 h post-administration of BSH, with a spread in values that resembled that previously reported in other experimental models and human subjects. The boron concentration ratios tumor/normal pouch tissue and tumor/blood ranged from 1.3 to 1.8. No selective tumor uptake was observed at any of the time points evaluated. The times post-administration of BSH that would be therapeutically most useful would be 5, 7 and 9 h. The

  1. Isoforms of elongation factor eEF1A may be differently regulated at post-transcriptional level in breast cancer progression

    Directory of Open Access Journals (Sweden)

    Vislovukh A. A.

    2013-01-01

    Full Text Available Eukaryotic translation elongation factor 1A exists as two 98 % homologous isoforms: eEF1A1 (A1 and eEF1A2 (A2 which are tissue and development specific. Despite high homology in an open reading frame (ORF region, mRNAs coding for eEF1A1 and eEF1A2 are different in their untranslated regions (UTR, suggesting a possibility of their dissimilar post-transcriptional regulation. Aim. To analyze the existence of cis-acting motifs in the UTRs of EEF1A1/A2 mRNAs, to confirm the possibility of post-transcriptional control of eEF1A1 and eEF1A2 expression. Methods. An ensemble of bioinformatic methods was applied to predict regulatory motifs in the UTRs of EEF1A1/A2 mRNAs. Dual-luciferase reporter assay was employed to detect post-transcriptional regulation of eEF1A1/A2 expression. Results. Numerous regulatory motifs in the UTR of EEF1A1/A2 mRNAs were found bioinformatically. The experimental evidence was obtained for the existence of negative regulation of EEF1A1 and positive regulation of EEF1A2 mRNA in the model of breast cancer development. Conclusions. EEF1A1 and EEF1A2 mRNAs contain distinct motifs in the UTRs and are differently regulated in cancer suggesting the possibility of their control by different cellular signals.

  2. Influence of bellyboard on the volume and dose of small bowel in three-dimensional conformal radiation therapy of post-operative Stage II + III rectum cancer

    International Nuclear Information System (INIS)

    Objective: To prospectively assess the effect of bellyboard on volume and dose of small bowel in post-operative stage II + III rectum cancer patient treated with three-dimensional conformal radio- therapy. Methods: Nine patients with rectum cancer after radical operation were examined by sim-CT scan. Two sets of images were taken for the whole pelvis with or without bellyboard. A three-beam treatment plan of three-dimensional conformal radiation therapy was made by the XioCMS treatment planning system. The max dose, the mean dose and the dose on V5, V10, V15, V20, V25, V30, V35, V40, V45, V50, V55 were evaluated in the plan of two positions. Results: Of the two sets of plans, the mean dose of the plan with bellyboard was lower than without bellyboard (1749.4 cGy vs 2124.8 cGy, P=0.023). And the high-dose volume of the plan with bellyboard was smaller than without bellyboard (V50: 51.4 cm3 vs 57.7 cm3, P 0.319). However, the low dose volume was signicantly larger than that in the plan with bellyboard(V5: 376.3 cm3 vs 230.1 cm3, P =0.001). And the mean dose(3557.0 cGy vs 4036.1 cGy, P=0.001)and V15-V50 of the bladder were significantly reduced by the bellyboard. Conclusion: The use of bellyboard signicantly reducess the mean dose in small bowel and bladder, and increases the low-dose volume of small bowel for post-operative stage II + III rectum cancer patient when treated with three-dimensional conformal radiotherapy. (authors)

  3. Objective and subjective factors as predictors of post-traumatic stress symptoms in parents of children with cancer--a longitudinal study.

    Directory of Open Access Journals (Sweden)

    Annika Lindahl Norberg

    Full Text Available BACKGROUND: Parents of children with cancer report post-traumatic stress symptoms (PTSS years after the child's successful treatment is completed. The aim of the present study was to analyze a number of objective and subjective childhood cancer-related factors as predictors of parental PTSS. METHODS: Data were collected from 224 parents during and after their child's cancer treatment. Data sources include self-report questionnaires and medical records. RESULTS: In a multivariate hierarchical model death of the child, parent's perception of child psychological distress and total symptom burden predicted higher levels of PTSS. In addition, immigrants and unemployed parents reported higher levels of PTSS. The following factors did not predict PTSS: parent gender, family income, previous trauma, child's prognosis, treatment intensity, non-fatal relapse, and parent's satisfaction with the child's care. CONCLUSIONS: Although medical complications can be temporarily stressful, a parent's perception of the child's distress is a more powerful predictor of parental PTSS. The vulnerability of unemployed parents and immigrants should be acknowledged. In addition, findings highlight that the death of a child is as traumatic as could be expected.

  4. Post Graduate Multidisciplinary Development Programme – Impact on the Interpretation of Pelvic MRI in Rectal Cancer Patients

    DEFF Research Database (Denmark)

    Pedersen, Bodil Ginnerup; Blomqvist, Lennart; Brown, Gina; Fenger-Grøn, Morten; Moran, Brendan; Laurberg, Søren

    2011-01-01

    . Objective: To assess the impact of a multidisciplinary team course for doctors in West Denmark on the technical quality, reporting and interpretation of pelvic MRI in rectal cancer. Design: Interventional, observational study. Two expert reviewers served as reference standard in the evaluation of...... consecutively performed pelvic MRI scans against which the evaluations from the participating centres were compared. Settings: Five imaging centres in West Denmark performing pelvic MRI in rectal cancer, from March 1, to December 31, 2007. Patients: One hundred and eighty patients with newly diagnosed rectal...... cancer were enrolled. Interventions: A multidisciplinary team course including on-site-visits. Main Outcome Measures: The MR-scans were evaluated concerning technical performance, reporting, interpretation and the ability to correctly allocate patients to chemo-irradiation based on imaging findings pre...

  5. Orofacial rehabilitation of patients with post-cancer treatment-An overview and report of three cases

    Directory of Open Access Journals (Sweden)

    K S Guttal

    2010-01-01

    Full Text Available According to World Health Organisation statistics, individuals of the Indian subcontinent have the highest prevalence of orofacial cancer. Surgery, radiation, chemotherapy or combination therapies are commonly administered treatment modalities for treatment of oral cancer. Surgical resection can be mutilating, disfiguring and may deeply affect self-image of patients. Orofacial defects have unique limitations and challenges. A coordinated effort from the surgeon, oral physician and the maxillofacial prosthodontist to treat such patients is the need of the hour. This article presents an overview of the orofacial rehabilitation of postcancer treatments along with case reports.

  6. Exercise may reduce depression but not anxiety in self-referred cancer patients undergoing chemotherapy. Post-hoc analysis of data from the 'Body & Cancer' trial

    DEFF Research Database (Denmark)

    Midtgaard, Julie; Stage, Maria; Møller, Tom;

    2011-01-01

    chemotherapy (The 'Body & Cancer' trial). Methods. Two hundred and nine self-referred patients (52 males, 157 females, mean age 47 years) were randomised into an intervention group and a waiting-list control group. Anxiety and depression was measured by the Hospital Anxiety and Depression Scale. Results. At......Abstract Background. The diagnosis and treatment of cancer may cause clinically significant and persistent psychological morbidity. The objective of this study was to determine the short-term effect of a six week exercise intervention on anxiety and depression in cancer patients undergoing...... baseline, 23.5% and 11.5% of the population scored >8 on the HADS and were classified as suspicious or definite cases of anxiety and depression, respectively. Adjusted for baseline score, disease and demographic covariates the estimated intervention effect showed improvement at six weeks for depression of...

  7. A randomized trial comparing radiotherapy alone versus radiotherapy with Geftinib in locally advance oral cavity cancer

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Singh

    2013-01-01

    Full Text Available Background: Concurrent chemo radiation is the current standard of care in locally advanced head and neck cancer, but in our set-up, all patients cannot be admitted for chemotherapy or cannot tolerate chemo radiation, or do not want surgery and/or surgery is not possible. The present study was planned to compare the efficacy of concomitantly administered Gefitinib with radiation therapy and radiation alone in locally advanced oral cavity cancer that are not fit or able to tolerate concurrent chemotherapy. Material and Methods: This was a single center, nonstratified, single blind, nonplacebo-controlled, parallel group intervention study with imbalanced randomization performed at our institute. Adult patients aged 40-65 years, male or female, irrespective of epidermal growth factor receptor (EGFR status, Karnofsky scale score more than 70, biopsy-proven SCC, locally advance oral cavity cancer, normal hematology parameters, renal function and liver function tests for normal before recruitment were enrolled in the study. Exclusion criteria were patients who were previously treated with either chemotherapy or radiotherapy (RT. Arm1 include only RT, whereas arm 2 includes Gefitinib with RT. Results: Sixty patients were included in the study, 30 in each arm. In Gefitinib plus RT arm, complete response was seen in 18 patients (60%, in only RT arm, complete response was seen in 10 patients (33.33%. There was no significant difference in acute toxicities and late toxicities. Conclusion: This study shows significant response to treatment and improvement in the Gefitinib plus RT as compared with RT alone. However, the findings of this study need to be confirmed by a study with a larger group of patients and a longer period of follow-up.

  8. Transforming growth factor-beta plasma dynamics and post-irradiation lung injury in lung cancer patients

    NARCIS (Netherlands)

    Novakova-Jiresova, A; van Gameren, MM; Coppes, RP; Kampinga, HH; Groen, HJM

    2004-01-01

    Purpose: To investigate the relevance of transforming growth factor-beta (TGF-beta) dynamics in plasma for identification of patients at low risk for developing pneumonitis as a complication of thoracic radiotherapy (RT). Patients and methods: Non-small cell lung cancer patients undergoing conventio

  9. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

    International Nuclear Information System (INIS)

    Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA

  10. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy

    Directory of Open Access Journals (Sweden)

    Versmessen Harijati

    2012-10-01

    Full Text Available Abstract Background Health-related quality of life (HRQOL assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR and hypofractionated tomotherapy (TT have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. Methods A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS or mastectomy (MA were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. Results On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms, nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better

  11. A prospective randomised controlled trial of concurrent chemoradiation versus concurrent chemoradiation along with gefitinib in locally advanced squamous cell carcinoma of head and neck

    Directory of Open Access Journals (Sweden)

    Biswamit Bhattacharya

    2014-01-01

    Full Text Available Background: The primary aim of the study was to find out whether addition of Gefitinib to standard cisplatin-based chemo-radiation can offer better treatment outcome at the cost of acceptable toxicities. Materials and Methods: Between January 2011 and June 2012, 64 patients were enrolled in the study following obtaining institutional ethical committee clearance and proper informed consent from the patients. Patients recruited were randomly allocated into a control arm (who received External Beam Radiotherapy with conventional 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy along with concomitant injection cisplatin at the dose of 30 mg/m 2 of body surface area on every week during radiation and study arm (who received radiotherapy with 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy, along with concomitant injection cisplatin at the dose of 30 mg/m 2 of body surface area on every week during radiation, plus Tablet Gefitinib (250 mg/day orally during the total duration of radiation treatment. However, only 61 patients (31 in the control arm and 30 in the study arm were available for analysis. The two groups were comparable in terms of age distribution, sex distribution, performance status, stage, primary site and histological grade. Results: 29.03% patients achieved complete response (CR in the control arm while 36.67% patients achieved CR in the study arm (CR, but the difference was not significant statistically (P = 0.5255. Total number of patients achieving overall response (CR + partial response in control arm was 19 (61.29% while it was 23 in the study arm (76.67%. However, the difference of overall response between the study arm and the control arm was not statistically significant (P = 0.1947. Disease free survival (DFS rate at 1 year was 22.58% for the control arm and 33.33% for the study arm but it was not statistically significant (P = 0.515. Addition of Gefitinib to standard concurrent cisplatin

  12. A phase I and pharmacokinetics study of intravenous calcitriol in combination with oral dexamethasone and gefitinib in patients with advanced solid tumors

    Science.gov (United States)

    Muindi, Josephia R.; Johnson, Candace S.; Trump, Donald L.; Christy, Renee; Engler, Kristie L.

    2009-01-01

    Purpose The primary objective of this study was to determine the maximum tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in combination with a fixed oral dose of dexamethasone and gefitinib in patients with refractory solid tumors. Methods A fixed oral dose of dexamethasone of 4 mg/day was given every 12 h × 3 doses starting 12 h prior to i.v. calcitriol administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and weekly thereafter. The starting calcitriol dose level was 57 μg and escalation occurred in cohorts of three patients until the MTD was defined. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Serum calcitriol PK studies were performed on day 1 (calcitriol + dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). Results A total of 20 patients were treated. Dose-limiting hypercalcemia was observed in two out of the four patients receiving 163 mcg/week of calcitriol. Mean (±SE) peak serum calcitriol concentration (Cmax) at the MTD (125 μg/week calcitriol) was 11.17 ± 2.62 ng/ml and the systemic exposure (AUC0–72 h) of 53.30 ± 10.49 ng h/ml. The relationship between calcitriol dose and either Cmax or AUC was linear over the 57–163 μg dose range. Conclusions The addition of a low dose of dexamethasone allowed the safe escalation of calcitriol to the MTD of 125 μg/week. This dose level resulted in serum calcitriol concentrations that are associated with pre-clinical antitumor activity. However, no antitumor activity was noted clinically in patients with solid tumors. PMID:19396601

  13. The importance of life quality questionnaire in patients with prostate cancer, pre- and post-radical prostatectomy

    OpenAIRE

    Gina A. Ciucă; Ovidiu Bratu; Dan Spînu; Marius Dinu; Cătălin Farcaș; Constantin A. Rădulescu; Robert Popescu; Dragoș Marcu; Dan Mischianu; Petru Armean

    2016-01-01

    This study analyzes the satisfaction of the patients with radical prostatectomy according to the signs and symptoms included in the EORTC QLQ – C30 and EORTC QLQ – PR25 questionnaires, including their relation with the health state that influences the pre and postoperative life quality. Fifty patients with prostate cancer in a localized stage were studied and analyzed in a prospective manner and for a period of 12 months, before and 6 months after the radical prostatectomy. In ...

  14. SU-E-T-14: A Feasibility Study of Using Modified AP Proton Beam for Post-Operative Pancreatic Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ding, X; Witztum, A; Kenton, O; Younan, F; Dormer, J; Kremmel, E; Lin, H; Liu, H; Tang, S; Both, S; Kassaee, A; Avery, S [UniversityPennsylvania, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Due to the unpredictability of bowel gas movement, the PA beam direction is always favored for robust proton therapy in post-operative pancreatic cancer treatment. We investigate the feasibility of replacing PA beam with a modified AP beam to take the bowel gas uncertainty into account. Methods: Nine post-operative pancreatic cancer patients treated with proton therapy (5040cGy, 28 fractions) in our institution were randomly selected. The original plan uses PA and lateral direction passive-scattering proton beams. Beam weighting is about 1:1. All patients received weekly verification CTs to assess the daily variations(total 17 verification CTs). The PA direction beam was replaced by two other groups of AP direction beam. Group AP: takes 3.5% range uncertainty into account. Group APmod: compensates the bowel gas uncertainty by expanding the proximal margin to 2cm more. The 2cm margin was acquired from the average bowel diameter in from 100 adult abdominal CT scans near pancreatic region (+/- 5cm superiorly and inferiorly). Dose Volume Histograms(DVHs) of the verification CTs were acquired for robustness study. Results: Without the lateral beam, Group APmod is as robust as Group PA. In Group AP, more than 10% of iCTV D98/D95 were reduced by 4–8%. LT kidney and Liver dose robustness are not affected by the AP/PA beam direction. There is 10% of chance that RT kidney and cord will be hit by AP proton beam due to the bowel gas. Compared to Group PA, APmod plan reduced the dose to kidneys and cord max significantly, while there is no statistical significant increase in bowel mean dose. Conclusion: APmod proton beam for the target coverage could be as robust as the PA direction without sacrificing too much of bowel dose. When the AP direction beam has to be selected, a 2cm proximal margin should be considered.

  15. Role of receptor tyrosine kinases in gastric cancer: New targets for a selective therapy

    Institute of Scientific and Technical Information of China (English)

    JC Becker; C Müller-Tidow; H Serve; W Domschke; T Pohle

    2006-01-01

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab,cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.

  16. The impact of hormone therapy on post-implant dosimetry and outcome following Iodine-125 implant monotherapy for localised prostate cancer

    International Nuclear Information System (INIS)

    Background and purpose: Many patients with localised prostate cancer present with symptoms of benign prostatic hypertrophy (BPH) and require neoadjuvant hormone therapy to shrink the gland before brachytherapy. The impact of this hormone therapy has been evaluated in 667 patients treated with Iodine seed monotherapy. Patients and methods: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. The mean age was 63 years (42-77 years). Three hundred and forty-six (51.9%) patients had a short course of neo adjuvant hormone therapy and 321 (49.1%) did not. The prescribed minimum peripheral dose was 145 Gy (TG43). Patients were followed up to a maximum of 8.2 years and a minimum of 18 months. Statistical analysis was performed to identify factors that would predict PSA relapse-free survival (PSA-RFS) defined by the American Society for Therapeutic Radiology and Oncology (ASTRO). Results: Overall the PSA relapse-free survival is 76.1 and 72.6% for patient cohorts being on pre-treatment hormones and not, respectively (P=0.107). Subdivided into risk groups the low risk group showed 92.5% PSA-RFS with hormones and 75.1% without (P=0.327). The intermediate group 75.7% with hormones and 72.9% without (P=0.148) and for the high-risk group 51.1% with and 51.1% without hormones (P=0.942). Evaluation of post-implant dosimetry in patients with and without hormone therapy showed that the D90 for those who received hormone therapy was 130.8 Gy compared with 145.1 Gy for those who did not (P<0.001). This may be related to the degree of oedema at the time of post-implant dosimetry. The CT to ultrasound prostate volume ratio was 1.17 for patients who received hormone therapy and 0.98 for those who did not (P<0.001). It is suggested that in the interval between stopping hormone therapy and doing post-implant dosimetry there was an increase in prostate volume, which results in a lower D90. Significant correlation was

  17. Pattern of External Breast Prosthesis Use by Post Mastectomy Breast Cancer Patients in India: Descriptive Study from Tertiary Care Centre.

    Science.gov (United States)

    Ramu, D; Ramesh, Rakesh S; Manjunath, Suraj; Shivakumar; Goel, Vipin; Hemnath, G N; Alexander, Annie

    2015-12-01

    In India, Breast cancer is now the most common cancer in urban and 2nd most common in rural areas [1]. The incidence is rising, more younger women are getting affected and due to increase in survival rates there is an increase in the total number of women suffering from breast Cancer. So far there are no studies evaluating the pattern of breast prosthesis use in Indian scenario. The aim of this study is to address the patterns of external breast prosthesis used in India and view of Indian women on such prosthesis after mastectomy for breast cancer. This was a descriptive longitudinal study. In this study we interviewed (telephonic) 63 people, after three years of completing treatment under The Department of Surgical Oncology, St. Johns medical college, Bangalore. Among the study group, 27 members (40 %) were using various prosthesis, rest 36 women were not using any type of prosthesis. Among the users of prosthesis, silicon prosthesis was used by 6 women, padded cups by 8 women, cloth or cotton by 12 women and 1 woman used other type of prosthesis. Most women use simple items like cloth and cotton (44 %). Next most commonly used prosthesis are padded cups(). Only 22 % of women were found using silicon prosthesis in this study. Most of the well educated patients used external prosthesis either in the form of silicon prosthesis or padded cups. Most of women below age of 50 used external breast prosthesis. Use of prosthesis was more in urban compared to rural population (48 % vs 25 %). Prosthesis users worried more about the body image than women not using prosthesis. 25 % of women using prosthesis had body image issues where as only 5 % of non prosthesis users had such problems. Prosthesis users need improvement in terms of comfort, size, shape and affordability. Most common reasons for not using prosthesis are age, lack of motivation and awareness. Less than half of the women included in this study used external prosthesis after mastectomy for breast cancer

  18. SU-E-P-56: Dosimetric Comparison of Three Post Modified Radical Mastectomy Radiotherapy Techniques for Locally Advanced Left-Sided Breast Cancer and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Zhang, W; Lu, J; Wu, L; Wu, F; Huang, B; Li, D [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China)

    2015-06-15

    Purpose: To compare the dosimetry of post modified radical mastectomy radiotherapy (PMRMRT) for left-sided breast cancer using 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: We created ten sets of PMRMRT plans for ten consecutive patients and utilized two tangential and one or two supraclavicular beams in 3DCRT, a total of 5 beams in IMRT and two optimized partial arcs in VMAT. The difference in results between any two of the three new plans, between new and previous 3DCRT plans were compared and analyzed by ANOVA (α =0.05) and paired-sample t-test respectively. P values less than 0.05 were considered statistically significant. Results: Both IMRT and VMAT plans had similar PTV coverage, hotspot area and conformity (all p>0.05), and significantly higher PTV coverage compared with new 3DCRT (both p<0.001). IMRT plans had significantly less heart and left lung radiation exposure compared with VMAT (all p<0.05). The 3DCRT plans with larger estimated CTV displacement had better target coverage but worse OARs sparing compared to those with smaller one. Conclusion: IMRT has dosimetrical advantages over the other two techniques in PMRMRT for left-sided breast cancer. Individually quantifying and minimizing CTV displacement can significantly improve dosage distribution. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)

  19. SU-E-P-56: Dosimetric Comparison of Three Post Modified Radical Mastectomy Radiotherapy Techniques for Locally Advanced Left-Sided Breast Cancer and Beyond

    International Nuclear Information System (INIS)

    Purpose: To compare the dosimetry of post modified radical mastectomy radiotherapy (PMRMRT) for left-sided breast cancer using 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: We created ten sets of PMRMRT plans for ten consecutive patients and utilized two tangential and one or two supraclavicular beams in 3DCRT, a total of 5 beams in IMRT and two optimized partial arcs in VMAT. The difference in results between any two of the three new plans, between new and previous 3DCRT plans were compared and analyzed by ANOVA (α =0.05) and paired-sample t-test respectively. P values less than 0.05 were considered statistically significant. Results: Both IMRT and VMAT plans had similar PTV coverage, hotspot area and conformity (all p>0.05), and significantly higher PTV coverage compared with new 3DCRT (both p<0.001). IMRT plans had significantly less heart and left lung radiation exposure compared with VMAT (all p<0.05). The 3DCRT plans with larger estimated CTV displacement had better target coverage but worse OARs sparing compared to those with smaller one. Conclusion: IMRT has dosimetrical advantages over the other two techniques in PMRMRT for left-sided breast cancer. Individually quantifying and minimizing CTV displacement can significantly improve dosage distribution. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)

  20. [Response of Pharmaceutical Companies to the Crisis of Post-Marketing Clinical Trials of Anti-Cancer Agents -- Results of Questionnaires to Pharmaceutical Companies].

    Science.gov (United States)

    Nakajima, Toshifusa

    2016-04-01

    Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media. PMID:27220801

  1. Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial.

    Science.gov (United States)

    Crosbie, Emma J; Roberts, Chris; Qian, Wendi; Swart, Ann Marie; Kitchener, Henry C; Renehan, Andrew G

    2012-04-01

    Body mass index (BMI) is a major risk factor for endometrial cancer incidence but its impact on post-treatment survival is unclear. We investigated the relationships of BMI (categorised using the WHO definitions) with clinico-pathological characteristics and outcome in women treated within the MRC ASTEC randomised trial, which provides data from patients who received standardised allocated treatments and therefore reduces biases. The impact of BMI on both recurrence-free survival (RFS) and overall survival (OS) was analysed using the Cox regression models. An apriori framework of evaluating potential biases was explored. From 1408 participants, there were 1070 women with determinable BMI (median=29.1 kg/m(2)). Histological types were endometrioid (type 1) in 893 and non-endometrioid (type 2) in 146 women; the proportion of the latter decreasing with increasing BMI (8% versus 19% for obese III WHO category versus normal weight, p(trend)=0.003). For type 1 carcinomas, increasing BMI was associated with less aggressive histopathological features (depth of invasion, p=0.006; tumour grade, p=0.015). With a median follow-up of 34.3 months, there was no influence of BMI on RFS - adjusted HRs per 5 kg/m(2) were 0.98 (95% CI 0.86, 1.13) and 0.95 (0.74, 1.24), for type 1 and 2 carcinomas; and no influence on OS - adjusted HRs per 5 kg/m(2) were 0.96 (0.81, 1.14) and 0.92 (0.70, 1.23), respectively. These findings demonstrate an important principle: that an established link between an exposure (here, obesity) and increased incident cancer risk, does not necessarily translate into an inferior outcome following treatment for that cancer. PMID:22100903

  2. Metabolic Response on Post-therapy FDG-PET Predicts Patterns of Failure After Radiotherapy for Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Siegel, Barry A.; Dehdashti, Farrokh [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Grigsby, Perry W. [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States)

    2012-05-01

    Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and Materials: The records of 238 patients with cervical cancer were reviewed. All patients were treated with a combination of external radiotherapy and intracavitary brachytherapy. Two hundred and nineteen patients (92%) received concurrent chemotherapy. All patients underwent pretreatment FDG-PET, and posttherapy FDG-PET was performed within 8-16 weeks of the completion of radiotherapy. Posttherapy FDG-PET results were categorized as complete metabolic response (CMR), partial metabolic response (PMR), and progressive disease (PD). Failure patterns were categorized as none, isolated local failure (central pelvis {+-} pelvic lymph nodes), distant failure, or combined local plus distant failure. Results: Of the 91 patients (38%) who had a recurrence, 22 had isolated local failures, and 69 had distant failures (49 distant failures and 20 combined local plus distant failures). Of the 173 patients with a CMR, 40 (23%) experienced treatment failure. All 25 patients with PD experienced treatment failure, which was distant in 24 patients (96%). Among the 40 patients with PMR, no failure has been observed for 14 patients (35%). Of the 26 failures within the PMR group, 15 (58%) were limited to the pelvis. Differences in the patterns of failure between the three groups (CMR, PMR, PD) were statistically significant (chi-square test; p < 0.0001). Conclusions: The majority of failures after definitive radiotherapy for cervical cancer include distant failures, even in the setting of concurrent chemotherapy. PMR within the cervix or lymph nodes is more commonly associated with isolated local recurrence.

  3. Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Cordero, F.; Pardini, B.; Korenková, Vlasta; Vymetálková, Veronika; Bielik, Ludovít; Vodičková, Ludmila; Pitule, P.; Liška, V.; Matejka, V. M.; Levý, M.; Buchler, T.; Kubista, Mikael; Naccarati, Alessio; Vodička, Pavel

    2014-01-01

    Roč. 54, č. 9 (2014), s. 769-778. ISSN 0899-1987 R&D Projects: GA ČR GAP304/10/1286; GA ČR GPP304/11/P715; GA MZd NT14329; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : colorectal cancer * DNA instability * DNA repair Subject RIV: EB - Genetics ; Molecular Biology; EI - Biotechnology ; Bionics (BTO-N) Impact factor: 4.808, year: 2014

  4. Role of post-therapy 131Iodine SPECT-CT in risk stratification and management of patients with differentiated thyroid cancer

    International Nuclear Information System (INIS)

    contamination of skin and in 1/13 intermediate risk patient was changed to low risk category (thus changing the post ablation TSH suppression criteria). Conclusion: SPECT/CT data significantly altered the initial risk of recurrence estimates in 4 of 33 patients (12.12%) and changed subsequent patient management in 13 out of 33 patients (39.39%). This study suggests that 131Iodine SPECT/CT has a significant role in the management strategy of differentiated thyroid cancer

  5. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  6. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  7. The immune system during the pre-cancer and the early cancer period. IL-2 production by PBL from post-menopausal women with and without endometrial carcinoma.

    Science.gov (United States)

    Yron, I; Schickler, M; Fisch, B; Pinkas, H; Ovadia, J; Witz, I P

    1986-09-15

    We report on alterations in IL-2 production and cell proliferation following PHA stimulation of peripheral blood lymphocytes (PBL) from stage-I endometrial carcinoma (EC) patients, and on mechanisms involved in these alterations. Our study includes 3 groups: EC patients, post-menopausal women at high risk of developing EC, and age-matched healthy women. IL-2 production was markedly lower in most EC patients than in healthy controls. Varying levels of IL-2 were produced by PBL from women in the high-risk group. The proliferative response of PBL to PHA appeared to correlate with levels of IL-2 production. Our results suggest that macrophages are involved, in part, in the modulation of T-cell functions of EC patients. PMID:3488968

  8. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Horst F Zitzelsberger

    2009-12-01

    Full Text Available Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC, for example, activation of the receptor tyrosine kinase (RTK genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1 by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  9. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei; Wang, Mei; Weier, Jingly F.; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich G.

    2009-03-09

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  10. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    International Nuclear Information System (INIS)

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations. (authors)

  11. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    OpenAIRE

    Shih-Chieh Chang; Jin-Yuan Shih; Cheng-Yu Chang

    2011-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patie...

  12. Characteristics and outcomes of patients with advanced non-small-cell lung cancer who declined to participate in randomised clinical chemotherapy trials

    OpenAIRE

    Tanai, C; Nokihara, H; Yamamoto, S.; Kunitoh, H; Yamamoto, N.; Sekine, I.; Ohe, Y; Tamura, T.

    2009-01-01

    There are inadequate data on the outcomes of patients who declined to participate in randomised clinical trials as compared with those of participants. We retrospectively reviewed the patient characteristics and treatment outcomes of both participants and non-participants in the two randomised trials for chemotherapy-naive advanced non-small-cell lung cancer. Trial 1 compared four platinum-based combination regimens. Trial 2 compared two sequences of carboplatin plus paclitaxel and gefitinib ...

  13. Post-operative irradiation techniques for advanced larynx and hypopharynx cancer: a dosimetric comparison using anthropomorphic phantoms

    International Nuclear Information System (INIS)

    Objective: Using anthropomorphic phantoms, to compare the matchline inhomogeneity and spinal cord sparing aspects of 3 previously described post-operative irradiation techniques for patients status-post laryngectomy. Materials and Methods: Two anthropomorphic phantoms were constructed with human bones and tissue equivalent material. One was sectioned coronally and one sagittally/parasagittally. Both had a stoma placed 2 cm above the sternal notch. Film compressed between the sections served as the dosimetric tool. Simulation films were taken and fields outlined for 3 different techniques as follows: 1) University of Florida's (UF), Gainesville, 3-field, 2) modified Cleveland Clinic's (CC) Single Isocenter/Asymmetric Collimators (the matchline was feathered twice during this experiment) and 3) MD Anderson's (MDA) 3-field. Conformal blocks were constructed and ported to confirm accuracy. A formal treatment plan was completed and then executed on both phantoms to a scaled dose equivalent of 60 Gy to isocenter. The exposed film infrared optical density was converted into dose and then normalized to the prescription dose to yield isodose plots. Isodose zones exceeding 100% had to measure at least 15mm in diameter to be considered significant in accordance with ICRU Report 50 guidelines. Results: Table 1 indicates the degree of matchline inhomogeneity for each method with percent isodose values. Both the MDA and UF techniques provided a 1.0-1.5 cm non-irradiated spinal cord gap between the opposed laterals and AP supraclavicular (APS) fields while underdosing a considerable volume of tissue potentially at risk for recurrence along parasagittal planes at the level of field junction. The CC technique showed no such underdosed regions. Table 1. % Isodose Across Matchline. Anterior, Mid and Posterior coronal planes measure 4,7 and 9 cm deep from the anterior neck surface respectively. Conclusions: This anthropomorphic phantom dosimetric analysis suggests that all 3 methods

  14. Short-term effects of supplementary feeding with enteral nutrition via jejunostomy catheter on post-gastrectomy gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    WU Quan; YU Jian-chun; KANG Wei-ming; MA Zhi-qiang

    2011-01-01

    Background Most gastric cancer patients who undergo gastrectomy develop malnutrition.It is,therefore,crucial to establish an effective means to provide nutrition for these patients.To perform home enteral nutrition (EN) to ensure adequate nutritional intake in gastric cancer patients,we placed a jejunostomy catheter during gastric surgery.Most patients showed improved nutritional status.Methods Twenty-nine inpatients at our hospital underwent radical gastrectomy and jejunostomy from December 2002 to December 2007 and were designated as the jejunostomy group,and 32 matched patients without a jejunostomy tube were designated as the tube-free group.The jejunostomy group was treated with EN from 72 hours to 3 months postoperatively.The tube-free group did not receive EN.Data including preoperative and postoperative body weight,body mass index (BMI),nutrition risk screening (NRS) score,Karnofsky performance score (KPS),and laboratory biochemical indicators were documented respectively and compared.Results Compared with preoperative week 1,both groups showed decreased body weight and BMI at 3 months postoperatively.The weight loss in the jejunostomy group ((7.1±3.3) kg) was significantly less than that in the tube-free group ((9.9±3.1) kg).Similarly,BMI decreased by (2.4+1.0) kg/m2 in the jejunostomy group,which was significantly less than in the tube-free group ((3.2±0.9) kg/m2).The number of patients with postoperative NRS ≥3 was decreased in the jejunostomy group,but was increased in the tube-free group,and this difference was significant.There were no significant differences between the two groups in total lymphocyte count,hemoglobin,albumin and prealbumin,and adverse drug effects.Conclusions Short-term (3 months) EN supplementation via jejunostomy tube can reduce the risk of malnutrition and weight loss,and improve tolerance of chemotherapy.Tube feeding is reliable for achieving these goals because it is not important whether or not the patients have appetites.

  15. Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  16. cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Wallner Kent E

    2009-07-01

    Full Text Available Abstract Background To evaluate the impact of external beam radiation therapy (XRT on weekly ultrasound determined post-void residual (PVR urine volumes in patients with prostate cancer. Methods 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66 or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59. All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. Results The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively. Patients with a larger baseline PVR (>40 cc had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR ( Conclusion Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.

  17. cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

    International Nuclear Information System (INIS)

    To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes

  18. Influential factors on the effectiveness of 131I treatment on post-surgical differentiated thyroid cancer patients

    International Nuclear Information System (INIS)

    Objective: To investigate the influential factors on the effectiveness of the first 131I ablation therapy on thyroid remnant and of 131I treatment on metastatic lesions in differentiated thyroid cancer (DTC) patients. Methods: Retrospectively, 46 DTC cases (divided into complete-ablation group and incomplete-ablation group) of first 131I ablation were enrolled, and 40 DTC cases (divided into remission group and in-remission group) of consecutive 131I treatments on metastatic lesions were enrolled. Influential factors were analyzed (t-test, t'-test, χ2-test, Fisher exact test) and logistic regression analysis was performed. Results: For the first 131I ablation effectiveness, surgical method, remnant thyroid weight, thyroid stimulating hormone (TSH) level, interval between surgery and 131I ablation therapy,metastatic status were selected as influential factors (χ2 = 5.804, t' =-5.258, t' =7.376, χ2 = 8.867, χ2 = 8.615, all Pχ1 ( remnant thyroid weight) -3.149χ2 (lymph node metastasis) -3.373χ3 (distant metastasis). For metastatic treatment effectiveness, remission rate of papillary DTC was higher than that of follicular DTC, remission rate of patients with lymph node metastasis was higher than that of distant metastasis, remission rate of total thyroidectomy was higher than that of other types of thyroidectomy (Fisher exact test, χ2 = 7.278, Pχ4 ( TSH level) - 0.250χ5 (Tg level). Conclusions: Influential factors of success rate of the first 131I ablation therapy included surgical method, remnant thyroid weight, TSH level, interval between surgery and 131I ablation therapy and metastatic status, while determinant factors were thyroid remnant weight, lymph node metastatic status and distant metastatic status. The influential factors of success rate of 131I treatment on metastatic lesions included pathological type, surgical method, metastatic status, TSH level and Tg level, while determinant factors were TSH level and Tg level before the first 131I ablation

  19. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  20. Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to Chromosome 5q31.1: A Post-GWAS Study

    Science.gov (United States)

    Ke, Juntao; Lou, Jiao; Chen, Xueqin; Li, Jiaoyuan; Liu, Cheng; Gong, Yajie; Yang, Yang; Zhu, Ying; Zhang, Yi; Gong, Jing

    2015-01-01

    Large-scale genome-wide association studies (GWAS) have established chromosome 5q31.1 as a susceptibility locus for colorectal cancer (CRC), which was still lack of causal genetic variants. We searched potentially regulatory single nucleotide polymorphisms (SNPs) in the overlap region between linkage disequilibrium (LD) block of 5q31.1 and regulatory elements predicted by histone modifications, then tested their association with CRC via a case-control study. Among three candidate common variants, we found rs17716310 conferred significantly (heterozygous model: OR = 1.273, 95% confidence interval (95%CI) = 1.016–1.595, P = 0.036) and marginally (dominant model: OR = 1.238, 95%CI = 1.000–1.532, P = 0.050) increase risk for CRC in a Chinese population including 695 cases and 709 controls. This variation was suggested to be regulatory altering the activity of enhancer that control PITX1 expression. Using epigenetic information such as chromatin immunoprecipitation-sequencing (ChIP-seq) data might help researchers to interpret the results of GWAS and locate causal variants for diseases in post-GWAS era. PMID:26381143

  1. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  2. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer.

    Science.gov (United States)

    Sheng, Jin; Fang, Wenfeng; Yu, Juan; Chen, Nan; Zhan, Jianhua; Ma, Yuxiang; Yang, Yunpeng; Yanhuang; Zhao, Hongyun; Zhang, Li

    2016-01-01

    The effects of treatments to programmed death ligand-1 (PD-L1) expression is unknown. The aim of this study was to investigate the impact of neoadjuvant chemotherapy (NACT) on PD-L1 expression in non-small cell lung cancer (NSCLC) patients. PD-L1 expression was detected by immunohistochemistry (IHC) method in 32 paired tumor specimens pre and post-NACT. The positivity of PD-L1 on tumor cells (TCs) changed from 75% to 37.5% after NACT (p = 0.003). Cases with IHC score of 1, 2, 3 all underwent apparent decrease (p = 0.007). However, no significant changes were observed on tumour-infiltrating immune cells (ICs) (p = 0.337). Subgroup and semiquantitative analyses all presented similar results. Moreover, patients with response to NACT presented significantly reduced PD-L1 expression on TCs (p = 0.004). Although it was not confirmed by the Cox proportional hazard regression model, there was an apparent difference in disease-free-survival (DFS) between negative-to-positive switch of PD-L1 status and the contrary group (median DFS: 9.6 versus 25.9, p = 0.005). Our data revealed that antecedent chemotherapy for NSCLC may results in inconsistency of PD-L1 expression. PD-L1 expression is suggested to be monitored around treatment and on serial samples, at least, on the latest tumor specimen. PMID:26822379

  3. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients

    Science.gov (United States)

    Inoue, Akira; Yoshida, Kazushi; Morita, Satoshi; Imamura, Fumio; Seto, Takashi; Okamoto, Isamu; Nakagawa, Kazuhiko; Yamamoto, Nobuyuki; Muto, Satoshi; Fukuoka, Masahiro

    2016-01-01

    Background The Japan Guidelines of Lung Cancer Therapy recommend epidermal growth factor receptor-tyrosine kinase inhibitors as a first-line therapy for advanced/recurrent non-small cell lung cancer patients with epidermal growth factor receptor mutation. Although survival periods in recent reports of epidermal growth factor receptor-tyrosine kinase inhibitor treatment have been getting longer, the reasons why are unclear. We investigated the survival, prognostic factors and real-world treatment of non-small cell lung cancer patients with epidermal growth factor receptor mutation in clinical practice. Methods Non-small cell lung cancer patients (n = 1660) who started first-line treatment from January 2008 to December 2012 were enrolled. Patients were diagnosed with epidermal growth factor receptor mutation-positive advanced/recurrent non-small cell lung cancer by histology or cytology samples. The primary objective was to estimate overall survival. The secondary objectives were to determine prognostic factors, real-world treatment patterns and efficacy of gefitinib treatment. We calculated the treatment exposure rate for each treatment category using the following formula: exposure rate = person-years for the treatment category/total person-years × 100. Results The median overall survival was 30.8 months. Sex, age, histology, epidermal growth factor receptor mutation type, clinical stage and performance status affected overall survival. The exposure rates for all epidermal growth factor receptor-tyrosine kinase inhibitors, gefitinib and platinum-doublet chemotherapy were 62.1, 46.4 and 8.5% respectively. Overall 56.1% of patients were administered gefitinib as first-line therapy, and 39.0% were treated with ≥2 epidermal growth factor receptor-tyrosine kinase inhibitor regimens. The median progression-free survival in the first-line gefitinib group was 11.4 months. Factors affecting prognosis were sex, histology, clinical stage and performance status. Conclusion

  4. Dosimetric comparison for volumetric modulated arc therapy and intensity-modulated radiotherapy on the left-sided chest wall and internal mammary nodes irradiation in treating post-mastectomy breast cancer

    OpenAIRE

    Zhang, Qian; Yu, Xiao Li; Hu, Wei Gang; Chen, Jia Yi; Wang, Jia Zhou; Ye, Jin Song; Guo, Xiao Mao

    2015-01-01

    Background The aim of the study was to evaluate the dosimetric benefit of applying volumetric modulated arc therapy (VMAT) on the post-mastectomy left-sided breast cancer patients, with the involvement of internal mammary nodes (IMN). Patients and methods The prescription dose was 50 Gy delivered in 25 fractions, and the clinical target volume included the left chest wall (CW) and IMN. VMAT plans were created and compared with intensity-modulated radiotherapy (IMRT) plans on Pinnacle treatmen...

  5. The Pre-surgical and Post-surgical Treatment Experience of Patients with Lung Cancer%肺癌手术患者的手术前后护理体会

    Institute of Scientific and Technical Information of China (English)

    秦翠萍

    2014-01-01

    目的:探讨肺癌患者手术前后的护理措施。方法总结20例肺癌患者手术前后护理方法过程。结果老年人术后早期并发症达30%,症经过积极治疗和加强护理,所有患者均痊愈出院。结论对肺癌手术患者加强围手术期护理,可减少手术并发症和降低术后早期死亡率。%Objective The pre-surgical and post-surgical treatment of patients with lung cancer to be investigated.Methods Summarizing the pre-surgical and post-surgical treatment methods of 20 cases of patients with lung cancer.ResultsThe post-surgical complications incidence of elderly patients reaches to 30 percent,with active treatment and enhanced attendance,al patients are cured and discharged from hospital.Conclusion Enhancing perioperative nursing for patients with lung cancer could decrease the surgical complications as wel as the early postoperative mortality.

  6. Exogenous or endogenous TSH stimulation before radioiodine therapy of metastatic thyroid cancer patients? The answer from post-therapy whole-body scan

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: human thyroid-stimulating hormone (rhTSH) is a well establish preparation method for ablation therapy with 131I in patients with differentiated thyroid cancer (DTC). However, for residual or metastatic disease, the advantage of rhTSH-aided 131I compared with the conventional preparation with thyroid hormone withdrawal (THW) still is a subject of discussion. The aim of our study was to compare the efficacy of rhTSH versus THW preparation for 131I therapy of metastatic DTC, based on the post-therapeutic whole body scan (ptWBS) information. Material and methods: 10 DTC patients (4 female and 6 males; age: 53 ± 19 years) with iodine-avid metastasis (5 patients with lung, 2 with bone, 1 with lymph node, 1 with lung+bone+lymph node and 1 with lung+bone+hepatic), were submitted to several (mean per patient: 3.6) radioiodine therapeutic courses, between January 2004 and February 2013. Endogenous TSH stimulation was used in most treatments (n=28) but rhTSH was the choice in 12 therapies (once in 8 patients and twice in 2 patients). For every patient, the interval between two consecutive treatments with different stimulation methods was less than 11 months. Post-therapy WBS was performed one week after radioiodine administration. The radioiodine avidity for the metastatic lesions seen on the rhTSH-aided ptWBS was compared, on a within-patient comparison basis, to the radioiodine avidity for the metastatic lesions seen on the THW-aided ptWBS. Results: in patients with positive metastasis on ptWBS after THW, no visible radioiodine uptake was seen on rhTSH-aided ptWBS in 4 patients (2 cases of lung metastasis, 1 case of lymph node and 1 case of bone metastases). A significant reduction of 131I uptake was recorded in 4 cases (2 with pulmonary, 1 with lung+bone+lymph node and 1 with lung+bone+hepatic). No significant differences were detected between both TSH stimulation methods in the other 2 patients, 1 with pulmonary and the other with

  7. Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Hotta

    Full Text Available BACKGROUND: In advanced non-small-cell lung cancer (NSCLC, with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP has improved over the years and to what degree SPP correlates with overall survival (OS. METHODS AND FINDINGS: Median progression-free survival (MPFS time and median survival time (MST were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r(2 to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001 in parallel to the increase in MST (11.253-day increase per year; p<0.001; MPFS improved little (1.863-day increase per year. Overall, a stronger association was observed between MST and SPP (r(2 = 0.8917 than MST and MPFS time (r(2 = 0.2563, suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r(2 = 0.4428, 0.7242, and 0.9081 in 1988-1994, 1995-2001, and 2002-2007, respectively. CONCLUSIONS: SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials.

  8. Research Progress on Resistance Mechanisms of Epidermal Growth Factor Receptor 
Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuan LI

    2012-02-01

    Full Text Available With a greater understanding of tumor biology, novel molecular-targeted strategies that block cancer progression pathways have been evaluated as a new therapeutic approach for treating non-small cell lung cancer (NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer in some populations of NSCLC patients. However, the efficacy of EGFR-TKIs is limited by either primary (de novo or acquired resistance after therapy. This review will focus on recently identified mechanisms of primary and acquired resistance to EGFR TKIs and strategies currently being employed to overcome resistance.

  9. The Effects of Dinner-to-Bed Time and Post-Dinner Walk on Gastric Cancer Across Different Age Groups: A Multicenter Case-Control Study in Southeast China.

    Science.gov (United States)

    Xu, Le; Zhang, Xi; Lu, Jun; Dai, Jia-Xi; Lin, Ren-Qin; Tian, Fang-Xi; Liang, Bing; Guo, Yi-Nan; Luo, Hui-Yu; Li, Ni; Fang, Dong-Ping; Zhao, Ruo-Hua; Huang, Chang-Ming

    2016-04-01

    Gastric cancer (GC) remains a major killer throughout the world. Despite the dramatic decrease in GC over the last century, its etiology has not yet been well characterized.This study investigated the possible independent and combined effects of the dinner-to-bed time and post-dinner walk on the risk for GC across different age groups.A population-based, case-control study was conducted in southeast China, including 452 patients with GC and 465 age-, race-, and gender-matched controls. A self-designed questionnaire was used to collect information on demographic characteristics, dinner-to-bed time, post-dinner walk, and other behavioral factors. Conditional logistic regression models were used to estimate the effects of the dinner-to-bed time and post-dinner walk as well as their joint effect on the risk for GC across different age groups.Individuals with dinner-to-bed time 55 years old. PMID:27100427

  10. Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: Results of the phase II RTCMIENDOMETRE French multicentre trial

    International Nuclear Information System (INIS)

    Purpose/objective: Whole “conventional” pelvic irradiation (up to 45–50 Gy) following hysterectomy is associated with a high rate of adverse gastro-intestinal (GI) adverse events, of which around 60% correspond to acute grade 2 toxicity. The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer. Materials/methods: Patients with post-operative stage Ib G3, Ic or II endometrial carcinomas with no history of chronic inflammatory bowel disease were eligible. Guidelines for volume delineation and dose prescription were detailed in the protocol. The investigators were advised to use a web-based atlas developed for the RTOG 0418 study. The dose of the vaginal and nodal PTV was 45 Gy in 25 fractions. To assess the ability of the participating centres to comply with the protocol guidelines, they were requested to complete a dummy run procedure before inclusion of their 1st patient. GI and genito-urinary (GU) toxicity were graded according to the CTCAE V 3.0 classification and were prospectively recorded every week during irradiation, as well as at time of brachytherapy insertions and during the follow-up visit at week 15 (W15). Special attention was given to note any changes to the grade of adverse events between W5 and W15. Results: From May 2008 to April 2010, 49 patients from 6 centres were recruited for the trial. One patient could not be treated, one patient died of vascular stroke at W3 without toxicity, and 1 patient refused to be followed-up after treatment. Thus, 46 cases were available for analysis at W15. The distribution by stage was as follows: Ib 16.3%, Ic 64.2%, II 20.4%. Thirty six patients (75%) received an additional vaginal vault boost of 6–10 Gy delivered by HDR brachytherapy in 1 or 2 fractions. Among the 47 patients who completed IMRT, 27% (95% CI 14.5–39.7%) developed at

  11. Targeting the EGFR pathway for cancer therapy

    DEFF Research Database (Denmark)

    Johnston, JB; Navaratnam, S; Pitz, MW; Maniate, JM; Wiechec, Emilia; Baust, H; Gingerich, J; Skliris, GP; Murphy, LC; Los, M

    Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally...... have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific...... side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e...

  12. Development of Nano-Liposomal Formulations of Epidermal Growth Factor Receptor Inhibitors and their Pharmacological Interactions on Drug-Sensitive and Drug-Resistant Cancer Cell Lines

    Science.gov (United States)

    Trummer, Brian J.

    A rapidly expanding understanding of molecular derangements in cancer cell function has led to the development of selective, targeted chemotherapeutic agents. Growth factor signal transduction networks are frequently activated in an aberrant fashion, particularly through the activity of receptor tyrosine kinases (RTK). This has spurred an intensive effort to develop receptor tyrosine kinase inhibitors (RTKI) that are targeted to specific receptors, or receptor subfamilies. Chapter 1 reviews the pharmacology, preclinical, and clinical aspects of RTKIs that target the epidermal growth factor receptor (EGFR). EGFR inhibitors demonstrate significant success at inhibiting phosphorylation-based signaling pathways that promote cancer cell proliferation. Additionally RTKIs have physicochemical and structural characteristics that enable them to function as inhibitors of multi-drug resistance transport proteins. Thus EGFR inhibitors and other RTKIs have both on-target and off-target activities that could be beneficial in cancer therapy. However, these agents exert a number of side effects, some of which arise from their hydrophobic nature and large in vivo volume of distribution. Side effects of the EGFR inhibitor gefitinib include skin rash, severe myelotoxicity when combined with certain chemotherapeutic agents, and impairment of the blood brain barrier to xenobiotics. Weighing the preclinical and clinical observations with the EGFR inhibitors, we developed the primary overall hypothesis of this research: that drug-carrier formulations of RTKIs such as the EGFR inhibitors could be developed based on nanoparticulate liposomal carriers. Theoretically, this carrier strategy would ameliorate toxicity and improve the biodistribution and tumor selectivity of these agents. We hypothesized specifically that liposomal formulations could shift the biodistribution of EGFR inhibitors such as gefitinib away from skin, bone marrow, and the blood brain barrier, and toward solid tumors

  13. A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members

    OpenAIRE

    Dawson Jeremy; Richardson Alison; McManus Chris; Collins Gary; Sippitt Joanna M; Taylor Cath; Richards Michael; Ramirez Amanda J

    2010-01-01

    Abstract Background The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer te...

  14. The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study

    International Nuclear Information System (INIS)

    Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression. We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined. APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles. APOA1 rs670 A/A carriage showed

  15. 吉非替尼/厄洛替尼致间质性肺疾病患者的临床特点及预后%Clinical characteristics and prognosis of patients with interstitial lung disease induced by gefitinib or erlotinib

    Institute of Scientific and Technical Information of China (English)

    刘晓琦; 杨敏

    2015-01-01

    Objective To explore the clinical characteristics and prognosis in patients with interstitial lung disease( ILD ) induced by gefitinib or erlotinib. Methods "Epidermal growth factor receptor tyrosine kinase inhibitors" "gefitinib" "erlotinib" "interstitial lung disease" "case report",and corresponding Chinese vocabularies were selected as key words and PubMed,MEDLINE,Web of Science, CNKI,Wanfang databases,VIP and CBMdisc from January 2001 to April 2014 were searched. The case reports of ILD induced by gefitinib or erlotinib were collected,the patients' age,sex,pathologic diagnosis and staging,anamnesis,history of treatment,ILD occurrence time,clinical manifestations,treatments and outcome were recorded. Results A total of 40 reports involving 60 patients were entered. Fifty-nine cases were diagnosed as non-small cell lung cancer. Thirty-five( 58. 3%) patients were treated with gefitinib,34 of them were given 250mg/d and one was given 500 mg/d. Twenty-five(41. 7%)cases were treated with erlotinib 150 mg/d. The shortest occurrence time of ILD was one day after medication,the longest time was 210 days after medication. Thirty-three(55. 0%)patients developed ILD during 7-28 days after medication. The major clinical manifestations of ILD due to gefitinib and erlotinib were dyspnea,cough and fever. Ten(16. 7%),2(3. 3%)and 2(3. 3%)cases developed erythra,diarrhea and liver injury at the same time,respectively. The patients who were diagnosed as ILD were withdrawn immediately and treated with symptomatic and harmonic therapy. Thirty patientsˊclinical symptom and imaging features were improved 3-90 days( median 10 days)later. Thirty patients died 1-80 days( median 6 days)later. The patients who were diagnosed as ILD in less than 7 days after medication,had history of pulmonary fibrosis or radiation pneumonitis,and developed liver injury meanwhile(4,2,2,respectively)died. Conclusions The median time of ILD induced by gefitinib or erlotinib was 24 days( 1-210 days ). The

  16. Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

    2016-03-01

    Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

  17. Closing the loop: an interactive action-research conference format for delivering updated medical information while eliciting Latina patient/family experiences and psychosocial needs post-genetic cancer risk assessment.

    Science.gov (United States)

    Macdonald, Deborah J; Deri, Julia; Ricker, Charité; Perez, Martin A; Ogaz, Raquel; Feldman, Nancy; Viveros, Lori A; Paz, Benjamin; Weitzel, Jeffrey N; Blazer, Kathleen R

    2012-09-01

    A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43 years. Among patients, 73 % had a breast cancer history; 85 % had BRCA testing (49 % BRCA+). Nearly all (96 %) attendees completed the conference surveys and ARS queries; ≥48 % participated in interactive discussions. Most (95 %) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research. PMID:22678665

  18. 洁悠神长效抗菌剂在外阴癌术后切口护理中的应用观察%Effect of Jieyoushen used in post-operative nursing care of Vulva cancer patients

    Institute of Scientific and Technical Information of China (English)

    张跃; 许秀梅; 陈兰英; 冒小平; 张燕

    2010-01-01

    Objective To observe the effect of the long-acting antibacterial material Jieyoushen used in post-operative nursing care of vulva cancer patients. Methods A total of 72 vulva cancer patients, after operation, were divided randomly into two groups (treated group and control group) , each consisting of 36 patients. For the control group, the patients were treated conventionally. The surgical site was disinfected with iodine cotton, irradiated with infrared rays and covered with germfree surgical dressing; while for the treated group, in addition to the conventional treatment, the surgical site and surrounding skin were sprayed with the long-acting antibacterial material Jieyoushen three times a day. The patients' post-operative pain, surgical site infection and healing were compared between groups. Results There was no obvious difference in post-operative pain between the two groups (P > 0. 05 ) , while there was obvious difference in infection and healing (P 0.05),切口感染和完全愈合天数情况比较差异有统计学意义(P<0.01).结论 在外阴癌术后切口护理中应用洁悠神喷洒切口及周围皮肤,能防止切口感染,缩短住院天数,减轻患者负担,值得在临床护理中推广使用.

  19. La Poste

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ The French Post Office has issued ten commemorative envelopes bearing original images depicting CERN and its history. This special fiftieth anniversary collector's edition will be available on the French Post Office (« La Poste ») stand at the Open Day on 16 October, in the CMS experiment hall at Cessy. Information for collectors: a pictorial postmark and date stamp have been specially designed and produced for the occasion with the assistance of CERN's graphics team. Sending a philatelic souvenir is a great way to commemorate the Open Day, so La Poste will be setting up a large post-box for that very purpose next to its stand. A perfect way to send images of CERN all around the world...

  20. Prospective randomised trial for the evaluation of the efficacy of low vs. high dose I-131 for post operative remnant ablation in differentiated thyroid cancer

    International Nuclear Information System (INIS)

    This study was performed under the auspices of IAEA project (i) to evaluate the efficacy of low (50 mCi) vs. high (100 mCi) dose I-131 for post operative remnant ablation in differentiated thyroid cancer and (ii) to search for factors associated with successful ablation. There were 138 cases of either papillary or follicular type without evidence of any metastasis. All patient had undergone at least subtotal thyroidectomy. Seventy-five were randomised to be treated with high dose and 63 with low dose I-131. Pretreatment total body scan and 24 hour-neck uptake were performed using 1 mCi of I-131, together with serum T4, TSH, Tg and antiTg. The criteria for successful ablation were absence of discrete thyroid bed activity in total body scan done using 3 mCi of I-131, 48-72 hour-neck uptake of less than 0.2% and serum Tg of less than 10 ng/ml. in the follow up done after 6-8 months of therapy. All patient characteristics were not significantly different between the two randomized groups. The overall successful ablation of the two groups was 76.8% (106/138). The success rate of therapy for each group is presented. High dose (100 mCi) I-131 is more efficient than low dose (50 mCi) for remnant ablation, even in cases with low neck uptake i.e. less than 10%. Logistic regression analysis confirmed the significant influence of ablative dose on the outcome with 4 times more chance of success using the high dose rather than the low dose. Baseline serum T4 and TSH were also associated with successful ablation with 1.4 times more chance of success with each 1 unit (mg/dl) of T4 decrease and 1.2 times with 10 units (mU/ml) of TSH increase. This might be, at least partly, due to good correlation between T4, TSH and the remnant mass

  1. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

    Science.gov (United States)

    Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-01-01

    Purpose This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response (≥50% decline), and time to skeletal-related event. Results Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02–2.24) for centrally assessed rPFS, 0.77 (0.28–2.15) for OS, 0.21 (0.08–0.51) for time to chemotherapy, and 0.31 (0.17–0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade ≥3 occurred in 33% of enzalutamide-treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97–1.10). Conclusions In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991). PMID:27195316

  2. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  3. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  4. Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors

    DEFF Research Database (Denmark)

    Midtgaard, Julie

    2013-01-01

    Sedentary behaviour and reduced exercise capacity are potential persisting effects of anti-cancer therapy that may predispose to serious health conditions. It is well-established that physical exercise may prevent some of these problems. However, the extent to which cancer survivors are able to...... adopt long-term physical activity habits depends largely on their motivation....

  5. Prevalence and risk of depressive symptoms 3-4 months post-surgery in a nationwide cohort study of Danish women treated for early stage breast-cancer

    DEFF Research Database (Denmark)

    Christensen, Søren; Zachariae, Robert; Jensen, Anders Bonde;

    2009-01-01

    breast cancer during the 2 1/2 year study period. Of these, 3343 women (68%) participated in a questionnaire study 12-16 weeks following surgery. Depressive symptoms (Beck's Depression Inventory II) and health-related behaviors were assessed by questionnaire. The Danish Breast Cancer Cooperative Group......BACKGROUND: Elevated levels of depressive symptoms are generally found among cancer patients, but results from existing studies vary considerably with respect to prevalence and proposed risk factors. PURPOSE: To study the prevalence of depressive symptoms and major depression 3-4 months following...... surgery for breast cancer, and to identify clinical risk factors while adjusting for pre-cancer sociodemographic factors, comorbidity, and psychiatric history. PATIENTS AND METHODS: The study cohort consists of 4917 Danish women, aged 18-70 years, receiving standardized treatment for early stage invasive...

  6. [Importance of Post-Marketing Studies in Gathering of Clinical Evidences for Proper Usage of Anti-Cancer Drugs, and the StudyRequirements for Their Credibility].

    Science.gov (United States)

    Inagaki, Osamu

    2016-04-01

    Pharmaceutical companies recognize the importance of post-marketing studies because they are crucial in the generation of clinical evidences for the usage of new medicines. To generate clinical evidences, quality of post-marketing studies should be well controlled from view point of "ethical conduction" and "reliability of results". In addition, control of conflict of interest (COI) between researchers and industries is also indispensable and is requested for the transparency of the studies. Japan Pharmaceutical Manufacturers Association(JPMA)stresses its commitment to the progressof transparency in post-marketing studies. PMID:27220799

  7. Association between the polymorphisms of angiotensin converting enzyme (Peptidyl-Dipeptidase A INDEL mutation (I/D and Angiotensin II type I receptor (A1166C and breast cancer among post menopausal Egyptian females

    Directory of Open Access Journals (Sweden)

    Rania Mohamed El Sharkawy

    2014-09-01

    Results: A statistically significant difference in AT1R A1166C SNP genotype frequencies was found among the studied groups. The patients group showed higher frequency of “CC” (2.9% vs 0% and “AC” (44.3% vs 24% and lower frequency of “AA” genotype (52.9% vs 76% than controls. The patients also showed significant higher frequency of allele “C” (25% vs 12% which was associated with increased breast cancer risk with an Odds ratio of 2.4444 (95% CI: 1.1967–4.9931. Testing the dominant model of inheritance revealed a statistically higher frequency of exposed genotypes “AC and CC” among the patients group (47.1% vs 24%, respectively; p = 0.013 with substantial increase in breast cancer risk among the exposed genotypes with an Odds ratio of 2.8243 (95% CI: 1.2679–6.2913. The present study demonstrated that (AC and CC genotypes of AT1R A1166C SNP and increased BMI can be considered as predictors for breast cancer risk among post menopausal Egyptian females. Results also revealed that A1166C SNP of AT1R gene and ACE/ID polymorphism could not be considered as predictors for breast cancer prognosis.

  8. A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

    Directory of Open Access Journals (Sweden)

    Chi-Tai Yeh

    2013-01-01

    Full Text Available Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs, was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA, was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

  9. Post radiation myxofibrosarcoma in breast: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jae Do; Kim, Ji Young; Hwang, Mi Soo; Bae, Young Kyung; Lee, Soo Jung [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2015-07-15

    Post radiation sarcoma is a very rare and invasive malignant tumor that occurs in patients who had radiation therapy 5-10 years ago for primary cancer such as breast cancer, lung cancer or lymphoma. In recent years, the incidence of post radiation sarcoma has increased, as patients survive longer after radiation therapy. We reported a case of surgically confirmed post radiation myxofibrosarcoma from the breast of a 59-year-old woman, with a discussion on the literature.

  10. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Latifi, K; Hoffe, S; Moros, E [Moffitt Cancer Center, Tampa, FL (United States); Saeed, Nadia [Brwon University, Providence, RI (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Shridhar, R [Florida Hospital, Orlando, FL (United States)

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  11. Monitoring post

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg; Jespersen, Andreas Maaløe

    2013-01-01

    This blog reports on the rumour that White House considers establishing a nudge unit similar to the UK Behavioural Insights Team. Given The Nudging Networks purpose and the work of the iNudgeYou-team this post is updated continuously to follow the US debate as it unfolds. Which issues are raised?......? How is the debate different from the one in the UK? And how does our work relate to the issues raised? The post has already been referenced in several US media, including US News....

  12. The Frequency of Epidermal Growth Factor Receptor Mutation of Nonsmall Cell Lung Cancer according to the Underlying Pulmonary Diseases

    Directory of Open Access Journals (Sweden)

    Kazuhiro Usui

    2011-01-01

    Full Text Available Background. Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs are effective in patients with nonsmall cell lung cancer with epidermal growth factor receptor (EGFR mutation, EGFR-TKIs have a risk of inducing fatal interstitial lung disease (ILD. The selection of chemotherapy based on the EGFR mutation status is recommended, however, the frequency of EGFR mutation in patients with ILD and the efficacy and safety of EGFR-TKI in patients with ILD and EGFR mutation are unknown. Methods. We retrospectively reviewed the association of the EGFR mutation status of nonsmall cell lung cancer and pulmonary diseases. Based on high-resolution computed tomography (HRCT performed at diagnosis of lung cancer, patients were categorized into three groups: normal, emphysema, and fibrosis. Results. Of 198 patients with nonsmall cell lung cancer, we identified 52 (26.3% patients with an EGFR mutation. EGFR mutations were identified in 43 (35.2% of 122 patients with normal lungs, 8 (13.6% of 59 with emphysema, and 1 (5.9% of 17 with pulmonary fibrosis. Of the 52 patients with EGFR mutation, 43 patients received gefitinib. One patient with an EGFR mutation and fibrosis developed fatal ILD. There was not a significant difference in median overall survival from gefitinib treatment between never-smokers and smokers (797 days versus not reached; =0.96. Conclusions. Patients with sensitive EGFR mutation and normal lungs may benefit from an EGFR-TKI treatment even if they have smoking history.

  13. Post-irradiation diarrhea

    International Nuclear Information System (INIS)

    In radiotherapy of pelvic cancers, the X-ray dose to be delivered to the tumour is limited by the tolerance of healthy surrounding tissue. In recent years, a number of serious complications of irradiation of pelvic organs were encountered. Modern radiotherapy necessitates the acceptance of a calculated risk of complications in order to achieve a better cure rate. To calculate these risks, one has to know the radiation dose-effect relationship of normal tissues. Of the normal tissues most at risk when treating pelvic tumours only the bowel is studied. In the literature regarding post-irradiation bowel complications, severe and mild complications are often mixed. In the present investigation the author concentrated on the group of patients with relatively mild symptoms. He studied the incidence and course of post-irradiation diarrhea in 196 patients treated for carcinoma of the uterine cervix or endometrium. The aims of the present study were: 1) to determine the incidence, course and prognostic significance of post-irradiation diarrhea; 2) to assess the influence of radiotherapy factors; 3) to study the relation of bile acid metabolism to post-irradiation diarrhea; 4) to investigate whether local factors (reservoir function) were primarily responsible. (Auth.)

  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

    Full Text Available Chih-Jen Yang,1–4 Ming-Ju Tsai,2,4 Jen-Yu Hung,2,3 Ta-Chih Liu,3,5 Shah-Hwa Chou,3,6 Jui-Ying Lee,6 Jui-Sheng Hsu,3,7 Ying-Ming Tsai,1,2,4 Ming-Shyan Huang,2–4 Inn-Wen Chong2,3 1Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, 3Faculty of Medicine, College of Medicine, 4Graduate Institute of Medicine, College of Medicine, 5Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 6Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 7Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Increased evidences show that epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear.Patients and methods: We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy, and overall survival (OS2, the OS in salvage therapy were recorded.Results: Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this

  15. Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

    International Nuclear Information System (INIS)

    The ATM protein is activated as a result of ionizing radiation, and genetic variants of the ATM gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for ATM mutations have been reported to have an increased risk of malignancy, especially breast cancer. Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the ATM gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant. A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the ATM gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient

  16. Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

    Directory of Open Access Journals (Sweden)

    Fosså Sophie D

    2007-07-01

    Full Text Available Abstract Background The ATM protein is activated as a result of ionizing radiation, and genetic variants of the ATM gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for ATM mutations have been reported to have an increased risk of malignancy, especially breast cancer. Materials and methods Norwegian breast cancer patients (272 treated with radiation (252 of which were evaluated for radiation-induced adverse side effects, 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR were screened for sequence variations in all exons of the ATM gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC followed by sequencing to determine the nature of the variant. Results and Conclusion A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala substitution in exon 11 (P-value 0.055 between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06. Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the ATM gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour

  17. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.

    Directory of Open Access Journals (Sweden)

    Emilie Cordina-Duverger

    Full Text Available BACKGROUND: There is extensive epidemiological evidence that menopausal hormone therapy (MHT increases breast cancer risk, particularly combinations of estrogen and progestagen (EP. We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen, and time interval between onset of menopause and start of MHT were examined. METHODS: We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls. Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. RESULTS: We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49 for progesterone-derived and 3.35 (1.07-10.4 for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. CONCLUSION: This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.

  18. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wairagu, Peninah M. [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Park, Kwang Hwa [Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Kim, Jihye [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Jung, Soon-Hee [Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Yong, Suk-Joong [Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Jeong, Yangsik, E-mail: yjeong@yonsei.ac.kr [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of)

    2014-05-09

    Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs.

  19. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    International Nuclear Information System (INIS)

    Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs

  20. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

    DEFF Research Database (Denmark)

    Pirker, Robert; Herth, Felix J F; Kerr, Keith M; Filipits, Martin; Taron, Miquel; Gandara, David; Hirsch, Fred R; Grunenwald, Dominique; Popper, Helmut; Smit, Egbert; Dietel, Manfred; Marchetti, Antonio; Manegold, Christian; Schirmacher, Peter; Thomas, Michael; Rosell, Rafael; Cappuzzo, Federico; Stahel, Rolf; de Stricker, Karin

    2010-01-01

    Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR...... tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker...

  1. Advances in the management of acquired resistance to EGFR-TKI in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Fei Zhou; Caicun Zhou

    2015-01-01

    Drugs that specifical y target the tyrosine kinase domain of epidermal growth factor receptor (EGFR), such as erlotinib or gefitinib, have exhibited striking ef icacy in non-smal cel lung cancer (NSCLC) patients har-boring activating EGFR mutations. However, acquired resistance inevitably develops and remains a serious barrier for the successful management of patients with this disease. Multiple mechanisms are reportedly involved in the process of acquired resistance, which provide new insights into the management of EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance. Here, we provide an overview of the emerging treatment approaches for patients with EGFR-TKI resistance.

  2. 甘氨双唑钠(CMNa)联合紫杉醇卡铂化疗对中晚期卵巢癌术后CA125升高的影响%Effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    Kaijian Lei; Yuming Jia; Jing Wang; Yiping Du

    2008-01-01

    Objective: To investigate the effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients. Methods: The effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in 25 post-operation advanced ovarian cancer patients were retrospectively analyzed and compared with those in 20 control cases. Results: After 1 cycle of chemotherapy, CA125 levels had decreasing trend compared with control, but had no statistical significance. While after two cycles of chemotherapy, CA125 levels decreased more rapidly compared with those in control. Side effects in two groups were alike. Conclusion: CMNa combined with paclitaxel and carboplatine has a stronger effect on the decrease of elevated CA125 levels than paclitaxel and carboplatin have in the treatment of post-operation advanced ovarian cancer, which indicates that CMNa has chemo-sensitizing effects on chemotherapy of paclitaxel and carboplatin.

  3. Gynecologic Malignancies Post-LeFort Colpocleisis

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2014-01-01

    Full Text Available Introduction. LeFort colpocleisis (LFC is a safe and effective obliterative surgical option for older women with advanced pelvic organ prolapse who no longer desire coital activity. A major disadvantage is the limited ability to evaluate for post-LFC gynecologic malignancies. Methods. We present the first case of endometrioid ovarian cancer diagnosed after LFC and review all reported gynecologic malignancies post-LFC in the English medical literature. Results. This is the second reported ovarian cancer post-LFC and the first of the endometrioid subtype. A total of nine other gynecologic malignancies post-LFC have been reported in the English medical literature. Conclusions. Gynecologic malignancies post-LFC are rare. We propose a simple 3-step strategy in evaluating post-LFC malignancies.

  4. Treatment of gastric cancer

    OpenAIRE

    Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; MABILIA, ANDREA; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically...

  5. Defining the target volume for post-operative radiotherapy after D2 dissection in gastric cancer by CT-based vessel-guided delineation

    International Nuclear Information System (INIS)

    Purpose: To determine the recurrent nodal gross tumor volume (rnGTV) based on CT-guided vascular structure to refine the clinical target volume (CTV) delineation in postoperative radiotherapy for advanced gastric cancer following radical gastrectomy with D2 dissection. Materials and methods: We retrospectively reviewed follow-up images from 91 patients with their first regional recurrence after D2 dissection in stage III gastric cancer with N3 disease. We defined rnGTV as recurrent nodes shown in follow-up CT images, in which one diagnostic radiologist with specialty of gastrointestinal tract investigated. We drew rnGTVs at the equivalent location based on the same vessels of reference comparing CT images to recurrence CT images. Results: We propose vessel-based locations of rnGTVs on CT images with axial and coronal views. We show different patterns of regional recurrence according to the location of primary gastric cancer using CT and digitally reconstructed radiograph (DRR) images. Frequently recurred sites, overlapped by more than five rnGTVs, are depicted in a DRR image. Conclusions: This study suggests vessel-based delineations of rnGTVs on CT images depending on nodal recurrence sites from follow-up images after D2 lymphadenectomy. Our results could help reduce the inter-observer variation of CTV delineation after D2 dissection in gastric cancer

  6. [Driver gene mutation and targeted therapy of lung cancer].

    Science.gov (United States)

    Mitsudomi, Tetsuya

    2013-03-01

    Although cancers may have many genetic alterations, there are only a few mutations actually associated with essential traits of cancer cells such as cell proliferation or evasion from apoptosis. Because cancer cells are "addicted" to these "drive genes" , pharmacologic inhibition of these gene function is highly effective. Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)(such as gefitinib or erlotinib)treatment of lung cancer harboring EGFR gene mutation is one of the prototypes of such therapies. Several clinical trials clearly demonstrated that progression-free survival of patients treated with EGFR-TKI is significantly longer than that of those treated by conventional platinum doublet chemotherapy. EGFR-TKI therapy dramatically changed the paradigm of lung cancer treatment. Furthermore, in 2012, crizotinib was approved for lung cancer treatment with anaplastic lymphoma kinase(ALK)gene translocation. Targeted therapies for lung cancers "addicted" to other driver gene mutations including ROS1, RET or HER2 are also under development. Through these personalized approaches, lung cancer is changing from an acute fatal disease to a more chronic disease, and eventually we might be able to cure it. PMID:23507588

  7. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC). A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression. A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7-85.2%), 87.5% (85.2-89.5%), 58.6% (52.6-64.5%) and 95.1% (93.5-96.5%), respectively. Similar estimates for the neck were 72.7% (66.6-78.2%), 87.6% (85.7-89.3%), 52.1% (46.6-57.6%) and 94.5% (93.1-95.7%), respectively. Scans done ≥12 weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate. The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy. (orig.)

  8. Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

    International Nuclear Information System (INIS)

    Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.

  9. Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhonghe; Yan Chao [Division of Radiation Oncology, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Zhang Zhiyuan; Zhang Chenping [Department of Oral and Maxillofacial Surgery, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Hu Haisheng; Tu Wenyong [Division of Radiation Oncology, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Kirwan, Jessica [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Mendenhall, William M., E-mail: mendwm@shands.ufl.edu [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida (United States)

    2011-12-01

    Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.

  10. Multiple Myeloma in Post Nuclear Accident Crisis

    OpenAIRE

    Wiwanitkit, Somsri; Wiwanitkit, Viroj

    2012-01-01

    The problem of 2011 nuclear accident crisis draws attention of physicians and medical scientists around the world. The cancer induction is an important adverse effect of exposure to radionuclide. In this specific article, the multiple myeloma, an important hematological cancer, in the post nuclear accident crisis will be discussed.

  11. Research on Upper Extremity Edema Post Breast Cancer Operation%乳腺癌术后上肢水肿研究现状

    Institute of Scientific and Technical Information of China (English)

    姚礼珑; 曹文兰

    2014-01-01

    目前乳腺癌的治疗方法有手术、放射治疗、化学治疗、内分泌治疗和靶向治疗等,综合治疗方法的逐渐规范使乳腺癌患者的生存状况得到改善[1],对于早期乳腺癌手术为其首选的治疗方法,结合术后辅助放射治疗。乳腺癌手术多对腋窝淋巴结进行清扫,影响上肢淋巴回流,上肢淋巴水肿是乳腺癌术后级放射治疗后最常见的并发症之一,文献报道其发生率约为6%~14%。乳腺癌术后引起的上肢水肿严重影响患肢的正常功能,造成患者生活不便,生存质量下降。本文将对乳腺癌术后引起的上肢水肿研究现状进行总结。%Breast cancer is one of the most common malignant tumors in current world, which is the first cause of cancer death in women[1] .At present the treatment of breast cancer are surgery, radiotherapy, chemotherapy and endocrine treatment and targeted thera-py, etc., and the gradually standardized comprehensive treatment method has improved the condition of patients with breast cancer.Up-per limb lymphedema is one of the most common complications after breast cancer, whose reported incidence rate is about 6%to 14%. It affects the normal function of sick limb seriously, causing inconvenience for patients and lowering the quality of life.This article sum-marizes the research status on upper extremity edema caused by breast cancer and postoperative radiotherapy.

  12. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  13. Living as a Breast Cancer Survivor

    Science.gov (United States)

    ... effects more likely to occur after breast cancer treatment include: Lymphedema Post-mastectomy pain syndrome Chemo brain If the cancer comes back (recurs) If cancer does recur, your treatment options will depend on the location of the ...

  14. Post petroleum

    International Nuclear Information System (INIS)

    In this original book-object, John Urry describes a world conditioned by an all-oil system. Our movement, possessions, and even our social relationships are entirely dependent on this rapidly-depleting energy source. He shows that the 20. century created the illusion of a future that, today, proves untenable, even in the medium term. While everyone's attention is still focused on just how long this reprieve will last, John Urry shifts the debate, asking the much more fundamental question: 'What happens next?' What would a world without oil look like? How would our lives as producers and consumers play out in a world deprived of this resource? In spite of growing awareness of the depletion of oil reserves, these questions remain unanswered. That is why the author alerts us to the need to prepare for post-oil now, and asks: without political awareness, how can our societies radically reinvent their relationship to energy and movement? John Urry thus imagines what will become of 'disconnected' societies in the form of four 'post-oil' scenarios, and calls us to action. His work is of particular importance to the Mobile Lives Forum, which aims to imagine good mobile lives for the future and prepare for the mobility transition. This text is transcript of a lecture given by John Urry to the Mobile Lives Forum's Scientific Steering Committee. Table of contents: 1 - Illusion: Understanding the energization of a social phenomenon; The birth of a new socio-technical system; United states: founders of an all-energy society; The emergence of an oil-based civilisation; Increasing difficulties in the use of oil; The role of oil in the current economic crisis; Can oil-dependency be deleted?; 2 - 4 scenarios: The Magic bullet future; digital lives; Unplugging: a post-car society; Warlordism in a world of shortages; 3 - Conclusion

  15. Evaluation of the walk-through inflatable colon as a colorectal cancer education tool: results from a pre and post research design

    OpenAIRE

    Sanchez, Janeth I.; Palacios, Rebecca; Cole, Adrianna; O’Connell, Mary A.

    2014-01-01

    Background Colorectal cancer (CRC) is a disease that can be prevented through early detection. Through the use of effective educational tools, individuals can become better informed about CRC and understand the importance of screening and early detection. The walk through Inflatable Colon is an innovative educational resource developed to engage and educate communities on CRC and the importance of receiving screening at the appropriate ages. Methods The Inflatable Colon Assessment Survey (ICA...

  16. Post traumatic painful shoulder – a delayed clinical feature of upper lobe lung cancer in a 74 year-old male. - case report -

    OpenAIRE

    Oana-Cristina Arghir; Mihaela Trenchea; Mădălina Iliescu; Galie, N; Camelia Ciobotaru

    2014-01-01

    A 74 year old Caucasian man, presents with a 6 week history of right sided chest pain including traumatic related painful right shoulder. Shoulder minor contusion was diagnosed and partial managed by symptomatic treatment associated to rehabilitation. The pain was initially eased with nonsteroidal anti-inflammatory drug (NSAID) use and finally changed worsening. He has evidence of moderate COPD on spirometry and has been commenced on inhalers. An invasive primitive adenocarcinoma lung cancer ...

  17. SUSPICIOUS POST

    CERN Multimedia

    Relations with the Host States Service

    2001-01-01

    If you receive a suspicious letter or package in the post, please do not open it and contact the Fire Brigade Tel. 74444. They will contact the CERN Medical Service. This is especially important in today's current situation with regard to the Anthrax scare. For further information, the Permanent Mission of Switzerland to the International Organisations in Geneva recommends the following web sites:   http://www.admin.ch/ch/f/cf/brennpunkt/03.html http://www.who.int/emc-documents/zoonoses/whoemczdi986c.html

  18. Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Eunjin Jwa

    Full Text Available The locoregional recurrence (LRR rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1-2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT.In total, 390 patients with pT1-2N0M0 (n = 307 and pT1-2N1M0 (n = 83 breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.After a median follow-up period of 5.6 years (range, 0.6-11.3 years, 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01 and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04 were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03 was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

  19. p53 and c-erbB-2 but not bcl-2 are predictive of metastasis-free survival in breast cancer patients receiving post-mastectomy adjuvant radiotherapy in Taiwan

    International Nuclear Information System (INIS)

    Patients with breast cancer often receive radiotherapy after mastectomy if they are at a high risk of local recurrence, but the prognosis varies among patients. We conducted a study to evaluate p53, bcl-2 and c-erbB-2 as predictors of prognosis in breast cancer patients receiving post-mastectomy radiotherapy, which has not been well defined in the Taiwanese population. We recruited 74 consecutive patients with primary operable breast cancer who were treated with mastectomy followed by locoregional radiotherapy and studied the presence of p53, bcl-2 and c-erbB-2 expressions in tumor tissues by immunohistochemical staining. Associations between the protein expressions and clinical outcomes, including local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS), were evaluated. The median follow-up time was 55 months. Expressions of p53, bcl-2 and c-erbB-2 were observed in 14 (19%), 28 (38%) and 39 (53%) patients, respectively. Both p53 and c-erbB-2 were significant predictors of MFS. The 5-year MFS for p53-negative and p53-positive tumors were 61.2 and 35.7% (P=0.01) and 5-year MFS for c-erbB-2-negative and c-erbB-2-positive tumors were 71.3% and 42.2% (P=0.01). Whereas expression of bcl-2 protein is associated with favorable clinicopathological features, it was not related to LRFS, MFS or OS. Multivariate analyses confirmed c-erbB-2 and p53 expressions as predictors of MFS independent of tumor size, histological grading and lymph node involvement. Expressions of p53 and c-erbB-2 are independent predictors of MFS in this Taiwanese population. Further research should be conducted on their application in the treatment and follow-up of patients. (author)

  20. Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain

    Directory of Open Access Journals (Sweden)

    Koizumi Mitsuru

    2010-08-01

    Full Text Available Abstract Background Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs or survival (cause specific death, CSD, retrospectively. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis. Results Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not

  1. Post traumatic painful shoulder – a delayed clinical feature of upper lobe lung cancer in a 74 year-old male. - case report -

    Directory of Open Access Journals (Sweden)

    Oana-Cristina Arghir

    2014-02-01

    Full Text Available A 74 year old Caucasian man, presents with a 6 week history of right sided chest pain including traumatic related painful right shoulder. Shoulder minor contusion was diagnosed and partial managed by symptomatic treatment associated to rehabilitation. The pain was initially eased with nonsteroidal anti-inflammatory drug (NSAID use and finally changed worsening. He has evidence of moderate COPD on spirometry and has been commenced on inhalers. An invasive primitive adenocarcinoma lung cancer was confirmed by chest CT scan and lymphnode biopsy through mediastinoscopy

  2. Feasibility of 5-days-on/2-days-off UFT/leucovorin in post-operative long-term adjuvant chemotherapy for colorectal cancer

    OpenAIRE

    TOKUNAGA, YUKIHIKO; Sasaki, Hirokazu

    2012-01-01

    Previous clinical studies have shown that the oral uracil/tegafur (UFT)/leucovorin (LV) regimen, in which the drugs are taken for 28 consecutive days every 35 days, is equivalent to an infusional 5-fluorouracil (5-FU)/LV regimen for the treatment of colorectal cancer. A 5-days-on/2-days-off schedule for UFT/LV has been proposed as the same schedule for UFT has been reported to be safe and have good compliance. However, few studies have been performed with regards to the feasibility of the UFT...

  3. Dosimetric results in implant and post-implant and low rate in brachytherapy prostate cancer with loose seeds and attached; Resultados dosimetricos en el implante y post-impante en braquiterapia de baja tasa en cancer de prostata con semillas sueltas y unidas

    Energy Technology Data Exchange (ETDEWEB)

    Juan-Senabre, X. J.; Albert Antequera, M.; Lopez-Tarjuelo, J.; Santos Serra, A.; Perez-Mestre, M.; Sanchez Iglesias, A. L.; Conde Moreno, A. J.; Gonzalez Vidal, V.; Beltran Persiva, J.; Muelas Soria, R.; Ferrer Albiach, C.

    2015-07-01

    The objective is determine differences dosimetry statistics on the dosimetry of the implant and post-implant in brachytherapy of low rate with implants permanent in prostate using seed of 125-I loose and attached Both in lives and in the post-prostatic plans dosimetric coverage is good and restrictions in urethra and rectum for both groups of patients are met. Not migrating with joined is evident, as well as better dosimetric homogeneity. (Author)

  4. New methods for determination of microbial adherence and colonization to bio material surface pre and post-irradiation treatment in cancer patients

    International Nuclear Information System (INIS)

    Biomaterials are being used with increasing frequency in medical fields in the saving of patients' lives and enhancing the quality of life for many others.Colonization of biomaterials by some pathogenic microorganisms depends on their ability to grow and adhere to the solid surface which then allows microorganisms to from bio films in which they are protected from host defense mechanisms and antimicrobial chemotherapy. Adherence and colonization followed by biofilm formation has been implicated as a potential virulence factor of some pathogenic strains responsible for catheter related infections in immuno-compromised cancer patients. Adherence assay and quantitation of bio films of microorganisms isolated and identified from catheter associated urinary tract infections from bladder cancer patients was performed by spectrophotometric method, hydrophobicities of some tested strains were also evaluated by adhesion to p-xylene, MICs of various antibiotics for isolated strains in conjunction with plasmid profiles and algD gene responsible for biofilm formation of selected strains were determined before and after in-vitro exposure to test dose of 24.14 Gy gamma radiation in studying the role of radiotherapy on the microorganisms and their virulence and also enable the design for new approaches to the prevention of serious microbial infections by interfering with adhesion process

  5. Assessing the Role of Volumetric Modulated Arc Therapy (VMAT) Relative to IMRT and Helical Tomotherapy in the Management of Localized, Locally Advanced, and Post-Operative Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To quantify differences in treatment delivery efficiency and dosimetry between step-and-shoot intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) for prostate treatment. Methods and Materials: Twenty-five prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated for: prostate alone (n = 5), prostate + seminal vesicles (n = 5), prostate + seminal vesicles + pelvic lymph nodes (n = 5), prostate bed (n = 5), and prostate bed + pelvic lymph nodes (n = 5). Target coverage, dose homogeneity, integral dose, monitor units (MU), and sparing of organs at risk (OAR) were compared across techniques. Time required to deliver each plan was measured. Results: The dosimetric quality of IMRT, VMAT, and HT plans were comparable for target coverage (planning target volume V95%, clinical target volume V100% all >98.7%) and sparing of organs at risk (OAR) for all treatment groups. Although HT resulted in a slightly higher integral dose and mean doses to the OAR, it yielded a lower maximum dose to all OAR examined. VMAT resulted in reductions in treatment times over IMRT (mean = 75%) and HT (mean = 70%). VMAT required 15-38% fewer monitor units than IMRT over all treatment volumes, with the reduction per fraction ranging from 100-423 MU from the smallest to largest volumes. Conclusions: VMAT improves efficiency of delivery for equivalent dosimetric quality as IMRT and HT across various prostate cancer treatment volumes in the intact and postoperative settings.

  6. Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1–2 tumor and 1–3 axillary lymph node(s) metastasis

    International Nuclear Information System (INIS)

    To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease. A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion

  7. Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen

    Directory of Open Access Journals (Sweden)

    Chamnanphon M

    2013-05-01

    .90%, and *36 (1 of 114, 0.90%; the CYP2C19 variant alleles were *2 (27 of 114, 23.70% and *3 (6 of 114, 5.30%. Kaplan–Meier estimates showed significantly shorter disease-free survival in patients with homozygous TT when compared to those with heterozygous CT or homozygous CC at nucleotides 100C>T and 1039C>T (CYP2D6*10 post-menopausal (log-rank test; P = 0.046. They also had increased risk of recurrence, but no statistically significant association was observed (hazard ratio 3.48; 95% confidence interval 0.86–14.07; P = 0.080.Conclusion: The CYP2D6 and CYP2C19 polymorphisms were not involved in tamoxifen efficacy. However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. As the number of breast cancer patients was relatively small in this study, results should be confirmed in a larger group of prospective patients.Keywords: CYP2D6, CYP2C19, disease-free survival, tamoxifen, pharmacogenetics, breast cancer

  8. Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Jixia Li

    2013-01-01

    Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

  9. Post-GWAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.

    Science.gov (United States)

    Barrdahl, Myrto; Canzian, Federico; Joshi, Amit D; Travis, Ruth C; Chang-Claude, Jenny; Auer, Paul L; Gapstur, Susan M; Gaudet, Mia; Diver, W Ryan; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Le Marchand, Loïc; Berg, Christine D; Chanock, Stephen J; Hoover, Robert N; Rudolph, Anja; Ziegler, Regina G; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Hankinson, Susan E; Lindström, Sara; Willet, Walter; Hunter, David J; Buring, Julie E; Lee, I-Min; Zhang, Shumin; Dossus, Laure; Cox, David G; Khaw, Kay-Tee; Lund, Eiliv; Naccarati, Alessio; Peeters, Petra H; Quirós, J Ramón; Riboli, Elio; Sund, Malin; Trichopoulos, Dimitrios; Prentice, Ross L; Kraft, Peter; Kaaks, Rudolf; Campa, Daniele

    2014-10-01

    We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 × 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC. PMID:24895409

  10. EGF receptor inhibitors increase ErbB3 mRNA and protein levels in breast cancer cells

    DEFF Research Database (Denmark)

    Grøvdal, Lene Melsæther; Kim, Jiyoung; Holst, Mikkel Roland;

    2012-01-01

    The potential benefits of drugs directly targeting the ErbB receptors for cancer therapy have led to an extensive development within this field. However, the clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited due to a high frequency of resistance. It has been reported...... gene expression of FAS which is involved in apoptotic signaling. Together, our data strongly suggest that resistance to EGFR inhibitors may result from the compensation of other family members and that combinations of anti-cancer drugs are required to increase the sensitivity of these treatments....... that, when inhibiting the epidermal growth factor receptor (EGFR) with the tyrosine kinase inhibitor gefitinib, increased activation of ErbB3 via MET, or by re-localization of ErbB3 mediates cell survival. Here we show further evidence that members of the ErbB receptor family facilitate resistance to...

  11. 外周血游离肿瘤DNA测定在非小细胞肺癌患者中的应用价值%Value of peripheral blood DNA determination by Ion Torrent in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    洪英财; 陈怀生; 林少霖; 王正; 杨林; 王光锁; 李富荣; 黄同海

    2015-01-01

    目的:探讨Ion Torrent测定外周血DNA在非小细胞肺癌中的临床价值。方法选择患者80例,通过Ion Torrent测序测定其EGFR浓度,观察EGFR浓度与EGFR基因型及与吉非替尼治疗敏感情况的关系,并分析EGFR突变与否者的1年生存率。结果突变型EGFR 32例,野生型EGFR 48例,吉非替尼敏感者30例,吉非替尼不敏感者50例,突变型EGFR浓度明显高于野生型EGFR (P<0.05),对吉非替尼治疗敏感者的血清EGFR浓度显著高于吉非替尼治疗不敏感者(P<0.05)。结论采用Ion Torrent测定外周血DNA技术了解患者基因型,有针对性的使用靶向治疗药物,其准确性更高,且能有效延长患者生存时间。%Objective To evaluate the clinical value of peripheral blood DNA determination by Ion Torrent in patients with non-small cell lung cancer. Methods Eighty patients of non-small cell lung cancer were enrolled, in which the epidermal growth factor receptor (EGFR) concentration was measured with Ion Torrent, Then the relation-ships between EGFR levels, EGFR genotype, and sensitive situation of gefitinib therapy were investigated, and one-year survival rate of the patients with or without EGFR mutation were analyzed. Results Among the 80 pa-tients, 32 had mutant EGFR and 48 had wild-type EGFR. Thirty patients were sensitive to gefitinib and 50 were not sensitive to gefitinib. Levels of EGFR in mutant EGFR was significantly higher than those in wild-type EGFR (P<0.05). And the levels were significantly higher in gefitinib-sensitive patients than patients not sensitive to gefitinib (P<0.05). Conclusion Peripheral blood DNA measured with Ion Torrent can ientify the patients’genotype and target therapies, which results in higher accuracy and prolonged survival time.

  12. [Advance of second-line chemotherapy in advanced non-small cell lung cancer.].

    Science.gov (United States)

    Zhang, Li

    2008-02-20

    There is a temporal disease-free period after 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC), most of patients need 2nd line chemotherapy. The recommended drugs in the 2nd line were docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Single docetaxel is the established therapy for second-line treatment of NSCLC.Pemetexem was validated its indication in the 2nd line in advanced NSCLC through a phase III randomised clinical trial which was compared with docetaxel. Although there were little toxicity, the further research can't find the survival benefit in high dose pemetrexed. EGFR-TKIs target therapy is a hot spot now. Gefitinib and erlotinib monotherapy have a good efficacy in the 2nd line. The research of gefitinib versus traditional chemotherapy manifested that its efficacy was no less than docetaxel, and was less toxicitity . The comparison of erlotinib with chemotherapy is going on. There are more and more other drugs proved their effect in the 2nd line, such as the efficacy of oral toptecan and vinflunine were similar to docetaxel. PMID:20727256

  13. Advance of second-line chemotherapy in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Li ZHANG

    2008-02-01

    Full Text Available There is a temporal disease-free period after 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC, most of patients need 2nd line chemotherapy. The recommended drugs in the 2nd line were docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs. Single docetaxel is the established therapy for second-line treatment of NSCLC.Pemetexem was validated its indication in the 2nd line in advanced NSCLC through a phase III randomised clinical trial which was compared with docetaxel. Althoughthere were little toxicity, the further research can't find the survival benefit in high dose pemetrexed. EGFR-TKIs target therapy is a hot spot now. Gefitinib and erlotinib monotherapy have a good efficacy in the 2nd line. The research of gefitinib versus traditional chemotherapy manifested that its efficacy was no less than docetaxel, and was less toxicitity . The comparison of erlotinib with chemotherapy is going on. There are more and more other drugs proved their effect in the 2nd line, such as the efficacy of oral toptecan and vinflunine were similar to docetaxel.

  14. Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: Long-term results focused on topographic pattern of locoregional relapse

    International Nuclear Information System (INIS)

    Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT. Methods: A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed. Results: Median follow-up was 72.6 months (range, 4–205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1–2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC. Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment

  15. Confirmation of a Low α/β Ratio for Prostate Cancer Treated by External Beam Radiation Therapy Alone Using a Post-Treatment Repeated-Measures Model for PSA Dynamics

    International Nuclear Information System (INIS)

    Purpose: To estimate the α/β ratio of prostate cancer treated with external beam radiation only by use of a model of long-term prostate-specific antigen (PSA) dynamics. Methods and Materials: Repeated measures of PSA from 5,093 patients from 6 institutions treated for localized prostate cancer by external beam radiation therapy (EBRT) without planned androgen deprivation were analyzed. A biphasic linear mixed model described the post-treatment evolution of PSA, rather than a conventional model of time to biochemical recurrence. The model was adjusted for standard prognostic factors (T stage, initial PSA level, and Gleason score) and cohort-specific effects. The radiation dose fractionation effect was estimated from the long-term rate of rise of PSA level. Results: Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long-term rate of change of PSA level (p = 0.0017 and p = 0.0003, respectively), an increase of each being associated with a lower rate of rise. The α/β ratio was estimated at 1.55 Gy (95% confidence band, 0.46-4.52 Gy). This estimate was robust to adjustment of the linear mixed model. Conclusions: By analysis of a large EBRT-only cohort along with a method that uses all the repeated measures of PSA after the end of treatment, a low and precise α/β was estimated. These data support the use of hypofractionation at fractional doses up to 2.8 Gy but cannot presently be assumed to accurately represent higher doses per fraction.

  16. Identification of pre- and post-treatment markers, clinical, and laboratory parameters associated with outcome in renal cancer patients treated with MVA-5T4

    Directory of Open Access Journals (Sweden)

    RobertAmato

    2013-07-01

    Full Text Available The recent approvals of immunotherapeutic agents (Sipuleucel-T and Ipilimumab for the treatment of different solid tumors gave a boost to the growing cancer immunotherapy field, even though few immunotherapy studies have demonstrated convincingly that there is a direct link between the predicted mode of action of an immunological compound and therapeutic benefit. MVA-5T4 (Trovax® is a novel vaccine combining the tumor-associated antigen 5T4 to an engineered vector-modified vaccinia Ankara (MVA. MVA helps to express the oncofetal 5T4 antigen and subsequently trigger a tumor-directed immune reaction. The safety and clinical benefit reported in multiple phase I and II clinical trials using MVA-5T4 were encouraging; immune responses were induced in almost all treated patients, and associations between 5T4-specific cellular or humoral responses and clinical benefit were reported in most of the nine phase II trials. In particular, clinical studies conducted in renal cell carcinoma (RCC patients have demonstrated an association between 5T4-specific (but not MVA antibody responses and enhanced survival. This review describes the clinical studies using MVA-5T4 conducted in RCC that convincingly demonstrated that an antigen-specific immune response induced by vaccination is associated with enhanced patient survival and is not simply a function of the general “health” of patients. We will also provide our expert opinions on possible future better-designed clinical trials based on relevant biomarkers. In addition, various combinations of MVA-5T4 and different and newer immunomodulator agents with promising clinical benefit will be discussed.

  17. Post-transcriptional and epigenetic regulation of antigen processing machinery (APM components and HLA-I in cervical cancers from Uighur women.

    Directory of Open Access Journals (Sweden)

    Ayshamgul Hasim

    Full Text Available Normal function of human leukocyte antigen class I (HLA-I and antigen processing machinery (APM proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in cancer development which was not described so far. Here we showed that the development of cervical intraepithelial neoplasia (CIN and cervical squamous cell carcinoma (CSCC in Uighur women was accompanied with the partial or total loss of protein expression of HLA-I, ß2-m and APM components, including the transporter associated with antigen processing (TAP1/2, low molecular mass protein (LMP2, LMP7, endoplasmic reticulum aminopeptidase 1(ERAP1, chaperone molecules include calreticulin (CLR, calnexin (CNX and ERp57, and this was proved again by analysis of transcription of the same genes in addition to three genes HLA-A, B and C coding for HLA-I. By bisulfite sequencing approach, we identified target CpG islands methylated at the gene promoter region of TAP1, TAP2, LMP7, tapasin and ERp57 in cervical carcinoma cells. Further analysis of CpG site specific methylation of these genes in cases of CSCC and CIN demonstrated an inverse correlation of altered CpG island methylation of TAP1, LMP7, and ERp57 with changes in protein expression. Moreover, promoter methylation of these genes was significantly higher in cases positive for human papillomavirus 16 (HPV 16 than negative ones. Our results suggested that epigenetic modifications are responsible for the aberrant expression of certain HLA-I and APM genes, and may help to understand unrevealed mechanisms of tumor escape from immune surveillance in cervical carcinogenesis.

  18. Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: A meta-analysis

    International Nuclear Information System (INIS)

    Background: We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). Methods: To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection. Results: Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p = 0.01) and 0.76 (p = 0.02) for PORT vs. controls, respectively). Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%. Conclusions: This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery

  19. Comparative evaluation of early and late whole body scan images post-therapy with I131 in patients with differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Aim: In order to reduce the period of time between the therapy with I131 and the acquisition of images for Whole Body Scan (WBS), the aim of this investigation is the comparison of WBS images acquired early (4th-6th days) and late (10th-15th days). Materials and Methods: 15 patients whit the diagnosis of Differentiated Thyroid Carcinoma (Follicular and Papillary) were included in the study. All of them received a therapeutic dose of Iodine 131 of 100 mCi. WBS images were obtained in one early control -4th - 6th day- and after 10-15 days post-therapy -late control-, using an SPECT system General Electric Starcam 3200 AC/T. The WB images were acquired in 512x128 matrix for anterior and posterior views. Their evaluation was performed blind and independently by 3 Nuclear Medicine Physicians, classifying the cases according a checklist 'with changes or without changes'. The signification of the results was evaluated by McNemar non parametric Test, using a significance level alfa=0.05. Results: 60% of patients showed some change between early and late controls. The change consisted of important descending or complete disappearance of I131 uptake focus in late control comparing with early evaluation. In the 33.3% of cases (44% of focus) is possible to observe total disappearance of focus described early. In 4 patients there were extra thyroidal metastasis, they didn't present reduction in their intensity of uptake and in one case the focus increased the uptake. Likewise, there was possible to determine the frequency of observation for the uptaking of Iodine 131 in normal sites. Conclusion: The changes observed between early and late evaluations an unacceptable loss of information which support the idea in order to evaluate with WBS images to the patient early (4th-6th day). This change is very appreciated in order to reduce the period between the therapy and control and it's a favourable support for the aim of this investigation

  20. Post stroke dementia and Post stroke depression

    OpenAIRE

    Trkanjec, Zlatko

    2012-01-01

    Stroke is the rapid loss of brain function due to disturbance in the blood supply to the brain causing predominantly motor and sensory symptoms. However, stroke can cause some other symptoms. Post stroke dementia and depression are probably the most important non-motor consequences of stroke. Post stroke dementia and depression are important and often overlooked symptoms following stroke. Treatment options for Post stroke dementia and depression are still limited, therefore diagnosis of Post ...

  1. Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary dissection in patients with breast cancer post-conservative surgery: impact on late toxicity

    International Nuclear Information System (INIS)

    The aim of the present work was to analyse the impact of mild hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after axillary dissection on late toxicity. From 2007 to 2012, 100 females affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were confirmed in all women. The median age at diagnosis was 60 years (range 34–83). Tumors were classified according to molecular characteristics: luminal-A 59 pts (59 %), luminal-B 24 pts (24 %), basal-like 10 pts (10 %), Her-2 like 7 pts (7 %). 82 pts (82 %) received hormonal therapy, 9 pts (9 %) neo-adjuvant chemotherapy, 81pts (81 %) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease control and treatment related toxicity were analysed in follow-up visits. The extent of lymphedema was analysed by experts in Oncological Rehabilitation. Within a median follow-up of 50 months (range 19–82), 6 (6 %) pts died, 1 pt (1 %) had local progression disease, 2 pts (2 %) developed distant metastasis and 1 subject (1 %) presented both. In all patients the acute toxicity was mainly represented by erythema and patchy moist desquamation. At the end of radiotherapy 27 pts (27 %) presented lymphedema, but only 10 cases (10 %) seemed to be correlated to radiotherapy. None of the patients showed a severe damage to the brachial plexus, and the described cases of paresthesias could not definitely be attributed to RT. We did not observe symptomatic pneumonitis. Irradiation of infra-supraclavicular nodes with a mild hypofractionated schedule can be a safe and effective treatment without evidence of a significant increase of lymphedema appearance radiotherapy related

  2. Medical treatment of advanced non-small cell lung cancer: progress in 2014

    Directory of Open Access Journals (Sweden)

    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

  3. The Prognostic Value of Irradiated Lung Volumes on the Prediction of Intra-/ Post-Operative Mortality in Patients after Neoadjuvant Radiochemotherapy for Esophageal Cancer. A Retrospective Multicenter Study.

    Science.gov (United States)

    Kup, Philipp Günther; Nieder, Carsten; Geinitz, Hans; Henkenberens, Christoph; Besserer, Angela; Oechsner, Markus; Schill, Sabine; Mücke, Ralph; Scherer, Vera; Combs, Stephanie E.; Adamietz, Irenäus A.; Fakhrian, Khashayar

    2015-01-01

    Purpose: To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S). Methods and Materials: Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection). Results: A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary

  4. Stressors in Breast Cancer Post-Treatment: a Qualitative Approach Factores estresantes del post-tratamiento del cáncer de mama: un enfoque cualitativo Estressores pós-tratamento do câncer de mama: um enfoque qualitativo

    Directory of Open Access Journals (Sweden)

    Gisele da Silva

    2010-08-01

    Full Text Available With the increasing effectiveness of breast cancer treatment, the scientific interest in investigating the quality of life of survivors has increased. However, research addressing the post-treatment period is still scarce. The aim of this study was to identify the stressors present in the lives of women in the one to five years post-diagnosis period. The sample was composed of 16 women assisted at a specialized mastectomy rehabilitation service. Data were collected through semi-structured interviews and analyzed using content analysis. The results indicate conflicts with self-image and alteration in the feeling of autonomy, fear in relation to the evolution of the condition, feelings of guilt about the disorder generated in the family, experience of disturbing social situations and a desire to return to their professional occupation. These results reveal the existence of stressors in this phase and the importance of support offered by psychosocial rehabilitation services for this population.Con la creciente resolutividad del tratamiento del cáncer de mama, ha aumentado el interés científico por la investigación de la calidad de vida de las sobrevivientes. Sin embargo, todavía son escasas las investigaciones que abordan el período post-tratamiento. Este estudio tuvo por objetivo identificar los factores estresantes presentes en la vida de mujeres en el período de uno a cinco años post-diagnóstico. Fueron investigadas 16 mujeres atendidas en un servicio especializado en rehabilitación de mastectomizadas. Los datos fueron recolectados mediante entrevista semiestructurada y analizados por medio del análisis de contenido. Los resultados indicaron conflictos con la autoimagen, alteración en la sensación de autosuficiencia, miedo en relación a la evolución del cuadro, sentimiento de culpa por el trastorno generado en la familia, vivencia de situaciones sociales perturbadoras y, deseo de retornar a la ocupación profesional. Esos

  5. Computed Tomography-Guided Core-Needle Biopsy Specimens Demonstrate Epidermal Growth Factor Receptor Mutations in Patients with Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Background: Target therapy with a new class of epidermal growth factor receptor (EGFR) inhibitors shows improved clinical response in EGFR gene-mutated lung cancers. Purpose: To evaluate the use of computed tomography (CT)-guided core-needle biopsy specimens for the assessment of EGFR gene mutation in non-small-cell lung cancer (NSCLC). Material and Methods: Seventeen (nine males, eight females) patients with advanced NSCLC were enrolled in this study. All patients underwent CT-guided core-needle biopsy of the lung tumor prior to treatment with the EGFR inhibitor gefitinib. There were no life-threatening complications of biopsy. The specimens were sent fresh-frozen for EGFR mutation analysis and histopathological study. Results: There were 12 (70.6%) EGFR gene mutants and five (29.4%) nonmutants. The objective response rate to gefitinib therapy was 73.3% (11 of 15 patients), with 91.7% (11 of 12 mutants) for the mutant group and 0% for the nonmutant group. Conclusion: CT-guided core-needle biopsy of advanced NSCLC enables the acquisition of sufficient tissue for EGFR gene mutation analysis

  6. The Microenvironment Matters: Estrogen Deficiency Fuels Cancer Bone Metastases

    OpenAIRE

    Wright, Laura E; Guise, Theresa A.

    2014-01-01

    Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth and a bone-resorptive phenotype in cancer cells. Post-menopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anti-cancer benefit of the bone-specific anti-resorptive agent zoledronic acid in the post-menopausal setting.

  7. Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M.

    Science.gov (United States)

    Costa, Daniel B; Kobayashi, Susumu S

    2015-12-01

    Epidermal growth factor receptor (EGFR) mutations, especially EGFR-exon 19 deletions and EGFR-L858R, are the most frequent actionable genomic events in lung adenocarcinomas. Tumors arise due to constitutively activated EGFR signaling and are susceptible to EGFR tyrosine kinase inhibitors (TKIs). First generation EGFR TKIs (gefitinib and erlotinib) and the second generation EGFR TKI afatinib are approved worldwide. Although targeted therapies against EGFR mutants induce dramatic initial responses, acquired resistance (through multiple biological mechanisms) to erlotinib, gefitinib and afatinib emerges within the first 1-2 years of continued monotherapy. EGFR-T790M accounts for more than half of acquired resistance to first or second generation EGFR TKIs by modifying ATP affinity and drug binding kinetics. Two new studies have shown that two covalent pyrimidine inhibitors-AZD9291 and rociletinib of EGFR-T790M (i.e., third generation EGFR TKIs) shown remarkable clinical activity in patients with acquired resistance to erlotinib, gefitinib and afatinib when the tumor carries EGFR-T790M in conjunction with an activating mutation. However, and regrettably, acquired resistance to these third generation EGFR TKIs has already been reported in preclinical models and clinical specimens; such as a tertiary mutation at EGFR-C797S that prevents covalent binding of EGFR TKIs. The experience with sequential EGFR TKI monotherapy highlights tumor heterogeneity and adaptability (i.e., relentless game of whack-a-mole played between TKIs and cancer), and will help shape future clinical development of novel combinatory approaches to manage EGFR mutated lung adenocarcinomas. PMID:26798593

  8. EGFR: The Paradigm of an Oncogene-Driven Lung Cancer.

    Science.gov (United States)

    Riely, Gregory J; Yu, Helena A

    2015-05-15

    Somatic, activating mutations in EGFR identify a significant minority of patients with non-small cell lung cancer (NSCLC). Although these mutations are associated with an approximately 70% response rate to some EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, and afatinib), patients develop resistance (i.e., "acquired resistance") after a median of 9 to 12 months. In patients with clinical acquired resistance, repeat biopsy of tumors has identified a number of relevant mechanisms of resistance, but by far the most frequent event is the acquisition of EGFR T790M, a mutation in the "gatekeeper" residue that confers resistance to gefitinib, erlotinib, and afatinib. This emphasizes the critical dependence upon EGFR signaling for some tumors, a property that has been exploited therapeutically. Dual EGFR blockade using afatinib and cetuximab led to a 29% radiographic response rate. More recently, drugs that target EGFR T790M (e.g., rociletinib, AZD9291, and others) have entered clinical trials, with impressive results observed in phase I clinical trials. The development of these newer drugs, with efficacy after resistance to first-line EGFR tyrosine kinase inhibitor, has led to exploration of these strategies in multiple disease settings: at resistance, in the first line, and in adjuvant treatment of those with completely resected early-stage disease who would otherwise die of recurrent/metastatic disease. This example of translational research that identifies mechanisms of resistance to first-generation drugs, and then targets those mechanisms yielding clinical benefit, is a paradigm for how targeted therapies can be developed. PMID:25979928

  9. Statins and Cancer Prevention

    Science.gov (United States)

    ... NCI Division of Cancer Prevention Web site at http://prevention.cancer.gov on the Internet. More information on cholesterol-lowering drugs can be obtained from the FDA Web site at http://www.fda.gov on the Internet. Related Resources Causes and Prevention Posted: June 2, ...

  10. Dosimetric comparison of two arcs VMAT plan and IMRT plan for breast cancer post-mastectomy%乳腺癌根治术后双弧VMAT与IMRT计划的剂量学比较

    Institute of Scientific and Technical Information of China (English)

    王佳浩; 李夏东; 邓清华; 吴稚冰; 夏冰; 赖建军; 唐荣军

    2014-01-01

    Objective To analyze the biophysical dosimetric characteristics and clinical application ability of VMAT technology for breast cancer post-mastectomy.Methods 28 patients with breast cancer (10 at left side and the other at right side) were planned in different ways respectively.One was two 90 degree arc VMAT plan and the other were 5 beam IMRT plan.The dosimetric parameters of two different plans including tumor control probability (TCP),conformity index(CI),homogeneity index (HI),V95and V110 in target,normal tissue complication probability (NTCP),V5,V20,V30 for ipsilateral lung,NCTP,D V25 for heart,D for the contralateral breast in OARs,MU and times were compared.Results The average tumor control probability (TCP) in VMAT and IMRT group was(96 ±2)% and (90 ±2)% (t =-6.28,P < 0.01),respectively.The PTV dose average homogeneity index (HI) of VMAT plans was better than that of IMRT plan (0.15 ±0.04 vs 0.22 ±0.02,t =13.29,P <0.01).For cancer position in left side,the mean dose of heart was decreased by 433.24 cGy in the VMAT plan.The NTCP of the hearts in VMAT plans had statistically significant difference compared with IMRT plans [(1.00±0.12)% vs (1.70±0.13)%,t =2.14,P <0.05].For plans of right breast cancer,the average mean dose of hearts in two control group was (3.27 ± 0.26) Gy and (6.00 ± 0.47) Gy (t =9.21,P<0.01).The total monitor unit (MU) was 530.7 in the VMAT arm and 693.9 in the IMRT arm (t =9.58,P <0.01).The treatment time was shorter in VMAT arm (t =8.40,P <0.05).Conclusions VMAT plans have better clinical value and more superior biophysical dosimetric characteristics for breast cancer post-mastectomy.%目的 比较乳腺癌根治术后双弧的容积旋转调强放射治疗(VMAT)与5野的静态调强放射治疗(IMRT)2种计划之间的剂量学差异,评估VMAT技术在乳腺癌根治术后的剂量学特点与应用能力.方法 选取28例乳腺癌根治术后患者(左侧10例,右侧18例),分别制定双90

  11. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  12. Nuclear EGFR as a molecular target in cancer

    International Nuclear Information System (INIS)

    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell’s nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future

  13. Impact of post-implant dosimetric parameters on the quality of life of patients treated with low-dose rate brachytherapy for localised prostate cancer: results of a single-institution study

    International Nuclear Information System (INIS)

    To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced

  14. SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFβ-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.

    Science.gov (United States)

    Xue, Xinying; Wang, Xin; Liu, Yuxia; Teng, Guigen; Wang, Yong; Zang, Xuefeng; Wang, Kaifei; Zhang, Jinghui; Xu, Yali; Wang, Jianxin; Pan, Lei

    2014-08-01

    A post-transcriptional pathway by which TGF-β modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-β for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-β induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-β treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-β-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma. PMID:24819169

  15. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ... potency post- surgery. So in 2008, while prostate cancer remains a very controversial subject, it is obviously ...

  16. Road to Recovery from Prostate Cancer

    Medline Plus

    Full Text Available ... more about robotic prostatectomies for the treatment of prostate cancer. During the program, we would like to go ... and potency post- surgery. So in 2008, while prostate cancer remains a very controversial subject, it is obviously ...

  17. THE INCIDENCE PROPORTION AND RISK FACTORS OF POST-MASTECTOMY PAIN SYNDROME IN BREAST CANCER SURVIVORS%乳腺癌术后疼痛综合征的前瞻性研究及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    辛玲; 冯艺

    2013-01-01

    目的:对国人乳腺癌术后疼痛综合征(post-mastectomy pain syndrome,PMPS)的流行病学特征进行调查,并对相关危险因素进行分析.方法:采用前瞻性队列研究对202例行择期乳腺手术的女性乳腺癌患者进行为期6个月的随访调查.应用ID-Pain患者自评量表评估慢性疼痛患者中神经病理性疼痛的发生率,并对16项相关危险因素进行统计学分析.结果:完成随访的200例患者中,42例(21%)出现PMPS.ID-Pain评分≥2分的患者有20例(47.6%),表明其疼痛类型可能是神经病理性疼痛.疼痛组与非疼痛组患者在年龄、术前焦虑抑郁、急性疼痛程度、腋淋巴结清扫、术前化疗方面有统计学差异(P<0.05).二分类变量Logistic回归分析表明年龄、术前焦虑抑郁、急性疼痛程度、腋淋巴结清扫是出现PMPS的独立危险因素.结论:PMPS在乳腺癌术后患者中占有一定比例.低龄以及合并术前心理异常的乳腺癌患者有可能发生PMPS.选择创伤相对较小的手术方式、做好术前心理干预以及术后急性期疼痛管理对预防PMPS可能有一定意义.%Objective: To assess the epidemiologic feature and risk factors of Post-mastectomy pain syndrome (PMPS) in Chinese population. Methods: 202 female breast cancer patients who underwent mastectomy were collected. A six months' follow-up was made and ID-Pain questionnaire was used to identify neuropathic pain. 16 risk factors of PMPS were analyzed, while binary logistic regression analysis was performed to determine the risk factors of PMPS. Results: 42 cases (21%) of 200 patients who completed the follow-up study were suffered from post-operative chronic pain. 20 patients from 42 cases (47.6%) suffered from neuropathic pain using ID-Pain questionnaire. Significant differences were found between painful patients and no pain patients on age, preoperative anxiety and depression, degree of postoperative acute pain, axillary lymph node dissection, and

  18. Linfadenectomía lumboaórtica asistida por robot en tumor residual postquimioterapia en cáncer testicular Robotic-assisted laparoscopic retroperitoneal lymph node dissection in post chemotherapy residual mass in testis cancer

    Directory of Open Access Journals (Sweden)

    OCTAVIO A CASTILLO C

    2011-10-01

    comparable to open surgery in terms of perioperative complications and oncological results, but its application in the post chemotherapy scenario is still matter of study. The development of robotic surgery and its advantages over laparoscopic surgery, make this an attractive option for complex procedures. We report our initial experience with robotic-assisted retroperitoneal lymph node dissection (R-RPLND. Methods: We describe the cases of two patients who underwent R-RPLND due to a Post Chemotherapy residual mass of a non-seminomatous testicular cancer. Results: Two patients, 27 and 30 years old, presented with retroperitoneal residual mass after 4 and 6 cycles of Bleomicin, Etoposide and Cis-Platinum. The first patient had a 4.3 cm left para-aortic mass and the other had a 6 cm mass behind the third portion of the duodenum. The mean surgical time was 255 minutes (210-300, with an estimated mean blood loss of 450 cc (100-800 and a mean hospital stay of 60 hours (72-48. The pathologic result was Teratoma in both cases. There was no periopera-tive morbidity. Conclusions: We believe that R-RPLND is a feasible and safe alternative in selected patients. However still needs more experience and longer follow up to asess its oncological outcome.

  19. Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics

    Directory of Open Access Journals (Sweden)

    Noguchi K

    2014-02-01

    Full Text Available Kohji Noguchi, Kazuhiro Katayama, Yoshikazu Sugimoto Division of Chemotherapy, Faculty of Pharmacy, Keio University, Tokyo, Japan Abstract: Adenine triphosphate (ATP-binding cassette (ABC transporter proteins, such as ABCB1/P-glycoprotein (P-gp and ABCG2/breast cancer resistance protein (BCRP, transport various structurally unrelated compounds out of cells. ABCG2/BCRP is referred to as a “half-type” ABC transporter, functioning as a homodimer, and transports anticancer agents such as irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38, gefitinib, imatinib, methotrexate, and mitoxantrone from cells. The expression of ABCG2/BCRP can confer a multidrug-resistant phenotype on cancer cells and affect drug absorption, distribution, metabolism, and excretion in normal tissues, thus modulating the in vivo efficacy of chemotherapeutic agents. Clarification of the substrate preferences and structural relationships of ABCG2/BCRP is essential for our understanding of the molecular mechanisms underlying its effects in vivo during chemotherapy. Its single-nucleotide polymorphisms are also involved in determining the efficacy of chemotherapeutics, and those that reduce the functional activity of ABCG2/BCRP might be associated with unexpected adverse effects from normal doses of anticancer drugs that are ABCG2/BCRP substrates. Importantly, many recently developed molecular-targeted cancer drugs, such as the tyrosine kinase inhisbitors, imatinib mesylate, gefitinib, and others, can also interact with ABCG2/BCRP. Both functional single-nucleotide polymorphisms and inhibitory agents of ABCG2/BCRP modulate the in vivo pharmacokinetics and pharmacodynamics of these molecular cancer treatments, so the pharmacogenetics of ABCG2/BCRP is an important consideration in the application of molecular-targeted chemotherapies. Keywords: kinase inhibitor, SNP, single-nucleotide polymorphisms, molecular target

  20. Study of heart rate variability in patients with cancer-related post traumatic stress disorders%癌症相关创伤后应激障碍患者心率变异性研究

    Institute of Scientific and Technical Information of China (English)

    潘雯; 吴爱勤

    2013-01-01

    目的:探讨癌症相关创伤后应激障碍(PTSD)患者的心率变异性(HRV). 方法:采用临床用创伤后应激功能障碍诊断量表(CAPS)对150例癌症患者进行诊断性访谈,并分为PTSD组(37例)和非PTSD组(nPTSD组,30例);应用PTSD自评量表(PCL-C)对两组患者进行评估;采用生理相干与自主神经平衡系统对PTSD组、nPTSD组、健康对照(NC)组(30名)进行短时HRV检测,分析HRV指标与PTSD核心症状的相关性. 结果:与nPTSD组和NC组比较,PTSD组平静状态下R-R间期标准差(SDNN)和高频功率(HF)较显著下降,低频功率(LF)/HF显著升高(P均<0.001);应激状态下PTSD组SDNN应激差值明显降低,HF和LF/HF应激差值显著增高(P均<0.001);HRV指标与PTSD核心症状的严重程度显著相关(P均<0.05). 结论:癌症相关PTSD患者自主神经功能紊乱,其核心症状的严重程度与自主神经功能紊乱显著相关.%Objective:To explore the heart rate variability (HRV) in patients with cancer-related post traumatic stress disorders (PTSD).Method:One hundred and fifty cancer patients had a diagnostic interviews with clinician-administered scale (CAPS) and were divided into the PTSD group (37 cases) and the nonPTSD (nPTSD) group (30 cases).The patients were assessed by PTSD checklist-civilian version (PCL-C).The short-term HRV was measured by the self-generate physiological coherence system in PTSD group,nPTSD group and normal control (NC) group (30 persons).The correlation between HRV index and core symptoms of PTSD were analyzed.Results:Compared with nPTSD group and NC group,the standard deviations of R-R intervals (SDNN) and high frequency power density (HF) in PTSD group were significantly lower,HF and low frequency power density (LF)/HF were significantly higher at resting (all P < 0.001).During stress,the change extent of SDNN was significantly lower,the change extent of HF and LF/HF were significantly higher (all P < 0.001).The HRV index were associated with the

  1. Review of the current targeted therapies for non-small-cell lung cancer.

    Science.gov (United States)

    Nguyen, Kim-Son H; Neal, Joel W; Wakelee, Heather

    2014-10-10

    The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALK-targeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come. PMID:25302162

  2. Cancer Statistics: Endometrial Cancer

    Science.gov (United States)

    ... a third party. HPF: Did You Know? Endometrial Cancer Endometrial Cancer - Did you know that endometrial cancer ... mfhs0vbvWi8?rel=0 SEER Stat Fact Sheets: Endometrial Cancer Expand All Collapse All Lifetime risk estimates are ...

  3. Noninvasive and real-time monitoring of molecular targeting therapy for lymph node and peritoneal metastasis in nude mice bearing xenografts of human colorectal cancer cells tagged with GFP and DsRed

    Science.gov (United States)

    Nakanishi, Hayao; Hara, Masayasu; Ikehara, Yuzuru; Tatematsu, Masae

    2007-02-01

    We have developed an in vivo imaging system consisting of GFP- and DsRed-tagged human colonic cancer cell line, which has peritoneal and lymph node metastatic potential and show high sensitivity to EGFR targeting drugs, and convenient detection devices for GFP and DsRed. The latter includes a small handy fluorescence detection device for external monitoring of the therapeutic effect of the drug and a convenient stereo fluorescent microscope for internal visualization of micrometastases. We applied this imaging system to investigate anti-metastatic effects of EGFR targeting drugs such as gefitinib (Iressa). This system allowed sensitive detection of the development of peritoneal and lymph node metastases from the micrometastasis stage at the cellular level and also permited noninvasive, non-anesthetic monitoring of anti-metastatic effect of the drug in an animal facility without any pretreatment. Significant decreases in the intraabdominal metastatic tumor growth and prevention of inguinal lymph node metastasis by gefitinib treatment could be clearly monitored. These results suggest that convenient, low-cost, true real-time monitoring of therapeutic effect using such a fluorescence-mediated whole body imaging system seems to enhance the speed of preclinical study for novel anti-cancer agents and will allow us to understand the action mechanism of molecular targeting drugs.

  4. Identification of drugs that restore primary cilium expression in cancer cells

    Science.gov (United States)

    Khan, Niamat Ali; Willemarck, Nicolas; Talebi, Ali; Marchand, Arnaud; Binda, Maria Mercedes; Dehairs, Jonas; Rueda-Rincon, Natalia; Daniels, Veerle W.; Bagadi, Muralidhararao; Raj, Deepak Balaji Thimiri Govinda; Vanderhoydonc, Frank; Munck, Sebastian; Chaltin, Patrick; Swinnen, Johannes V.

    2016-01-01

    The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties. PMID:26862738

  5. Focal therapy in prostate cancer

    OpenAIRE

    Bos, van den, G.A.M.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the prostate cancer may be focally treated followed by careful post-treatment evaluation, and if necessary by focal re-treatment. During the past decades, the age of men at prostate cancer detection has decr...

  6. Strategic Workshops on Cancer Nanotechnology

    OpenAIRE

    Nagahara, Larry A.; Lee, Jerry S.H.; Molnar, Linda K.; Panaro, Nicholas J.; Farrell, Dorothy; Ptak, Krzysztof; Alper, Joseph; Grodzinski, Piotr

    2010-01-01

    Nanotechnology offers the potential for new approaches to detecting, treating and preventing cancer. To determine the current status of the cancer nanotechnology field and the optimal path forward, the National Cancer Institute’s Alliance for Nanotechnology in Cancer held three strategic workshops, covering the areas of in-vitro diagnostics and prevention, therapy and post-treatment, and in-vivo diagnosis and imaging. At each of these meetings, a wide range of experts from academia, industry,...

  7. Post-Adolescent Issues

    Science.gov (United States)

    Search COPING & HEALING CARING FOR A CHILD: POST-ADOLESCENT ISSUES As your child reaches adulthood, there will ... intake. New issues that you and your post adolescent child may want to discus together with his/ ...

  8. 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

  9. Comparison of whole-body {sup 18}F-FDG PET, {sup 99m}Tc-MIBI SPET, and post-therapeutic {sup 131}I-Na scintigraphy in the detection of metastatic thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, Masahiro [Department of Radiology, Hikone Municipal Hospital, 1882 Hassakacho, 522-8539, Hikone, Shiga (Japan); Kasagi, Kanji [Department of Nuclear Medicine, Takamatsu Red Cross Hospital, Takamatsu (Japan); Misaki, Takashi [Radioisotope Center, Tenri Hospital, Tenri (Japan); Matsumoto, Keiichi; Nakamoto, Yuji [Institute of Biomedical Research and Innovation, Kobe (Japan); Iida, Yasuhiro; Ishimori, Takayoshi; Higashi, Tatsuya; Saga, Tsuneo; Konishi, Junji [Department of Nuclear Medicine and Diagnostic Imaging, Kyoto Graduate School of Medicine, Kyoto (Japan)

    2004-04-01

    The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile ({sup 99m}Tc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of {sup 99m}Tc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38-72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following {sup 131}I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and {sup 99m}Tc-MIBI SPET WBS at an interval of less than 1 week, followed by {sup 131}I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. {sup 131}I WBS was performed 3-5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, {sup 201}Tl and {sup 131}I scans). FDG-PET, {sup 99m}Tc-MIBI SPET and post-therapeutic {sup 131}I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight

  10. Cancer Statistics

    Science.gov (United States)

    ... What Is Cancer? Cancer Statistics Cancer Disparities Cancer Statistics Cancer has a major impact on society in ... success of efforts to control and manage cancer. Statistics at a Glance: The Burden of Cancer in ...

  11. Treatment of gastric cancer

    Science.gov (United States)

    Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; Mabilia, Andrea; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status PMID:24587643

  12. 78 FR 27408 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-10

    ... Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients. Date: June 4, 2013... Prevention Research; 93.394, Cancer Detection and Diagnosis Research; 93.395, Cancer Treatment Research; 93... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  13. Prediction of post-post-perovskite transitions

    Science.gov (United States)

    Umemoto, K.

    2008-12-01

    In the Earth, the post-perovskite structure is the final form of MgSiO3. However, in the solar giants and exoplanets in which pressure is much higher than the Earth, we can expect further phase transitions beyond the post-perovskite phase, i.e., post-post-perovskite transitions. Here we propose by first principles two candidates of crystalline post-post-perovskite phases of NaMgF3, which is a low-pressure analog of MgSiO3: U2S3-type and P63/mmc phases. Then we demonstrate that Al2O3 should undergo a transition to the U2S3-type phase at ~3.7 Mbar. This transformation should be important for the analysis of shock data in this pressure range, since alumina is used as window material. Our calculated compression curves agree with shock data excellently, suggesting the presence of two phase transitions (corundum-to-Rh2O3(II)-type and Rh2O3(II)-type-to-CaIrO3-type) in shock data. Our prediction also suggests that the multi-Mbar crystal chemistry of planet-forming minerals might be related to that of the rare-earth sulfides. Computations were performed at the Minnesota Supercomputing Institute. Research was supported by NSF grants EAR-0135533, EAR-0230319, and ITR-0428774 (VLab).

  14. Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

    DEFF Research Database (Denmark)

    Gärtner, Rune; Cronin-Fenton, Deirdre; Hundborg, Heidi Holmager;

    2010-01-01

    Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.......Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association....

  15. 6 Common Cancers - Prostate Cancer

    Science.gov (United States)

    ... PSA tests. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 10 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  16. 6 Common Cancers - Skin Cancer

    Science.gov (United States)

    ... advanced melanoma. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 12 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  17. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... certain people. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 11 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  18. NVP-BEZ235 overcomes gefitinib-acquired resistance by down-regulating PI3K/AKT/mTOR phosphorylation

    OpenAIRE

    Sun ZH; Li QH; Zhang S; Chen J; Huang LL; Ren JH; Chang Y; Liang YC; Wu G.

    2015-01-01

    Zhihua Sun,2,* Qiuhui li,1,* Sheng Zhang,1 Jing Chen,1 Lili Huang,3 Jinghua Ren,1 Yu Chang,1 Yichen Liang,1 Gang Wu1 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Oncology department, Xiangyang central Hospital, Xiangyang, Hubei, People’s Republic of China; 3Radiation Oncology Department, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic o...

  19. Sample Cancer Epidemiology Grant Applications

    Science.gov (United States)

    The National Cancer Institute frequently receives questions from investigators for examples of successfully funded grant applications. Several investigators agreed to let the Epidemiology and Genomics Research Program post excerpts of their grant applications online.

  20. 乳腺癌术后放疗3种治疗计划的剂量学研究%Dosimetric study of three different kinds of radiotherapy technique for post-operative breast cancer

    Institute of Scientific and Technical Information of China (English)

    周桂霞; 戴相昆; 徐寿平; 鞠忠建; 巩汉顺; 解传滨; 杜镭

    2010-01-01

    Objective To investigate the dosimetric characteristics of helical tomotherapy(HT),intensity-modulated radiation therapy(IMRT)and three.dimensional conformal radiation therapy(3D-CRT)for the post-operative breast cancer as well as their comparison in protecting the normal tissues.Methods The CT images of 10 postoperative patients with early stage breast cancer were transferRed into HT and IMRT and 3D- CRT planning system respectively after the target region and normal tissues were drawn out with the same doctor.Each prescribed dose for three kinds of plans was 50 Gy/25 fractions.Inrradiation doses and volume at heart and double lungs as well as conformity index(CI)and homogeneity index(HI)were evaluated.Results The PTV volume of prescribed target dose of 95% and 100%in HT, IMRT and 3D-CRT groups were 99.13%and 95.87%,97.80%and 94.05%,96.37%and 87.29%.respectively.The CI and HI in HT.IMRT and 3D-CRT groups were 0.80±0.10 and 1.09 ±0.03,0.65±0.07 and 1.14±0.02,0.40±0.08 and 1.17±0.04,respectively V5,V10 and V20 of the heart were the lowest at 3D-CRT than HT and lM RT.V5 of the diseased lung was the lowest at 3D-CRT compared to HT and IMRT.V5 and V10 of the healthy lung were the lowest at 3 D-CRT compared to other groups.Conclusions Compared with IMRT and 3D-CRT.HT technique in treating breast cancer had the best conformity index and homogeneity index as well as steeper dose gradient.Irradiated doses and volume at the heart was the lowest at 3D- CRT and the highest at IMRT.Irradiated doses and volume of the heart and healthy lung as well as the diseased lung were the lowest at 3D-CRT compared to HT and IMRT groups.%目的 评估螺旋断层调强放疗(helical tomotherapy, HT)、常规直线加速器逆向调强放疗(IMBT)和三维适形放疗(3D- CRT)3种治疗计划对乳腺癌术后胸壁照射的剂量影响和正常组织受照剂量体积对比.方法 选择10例早期乳腺癌改良根治术后患者CT定位图像,由同一医

  1. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  2. Vulva cancer

    Science.gov (United States)

    Cancer - vulva; Cancer - perineum; Cancer - vulvar; Genital warts - vulvar cancer; HPV - vulvar cancer ... cells. Other types of cancers found on the vulva are: Adenocarcinoma Basal cell carcinoma Melanoma Sarcoma Vulvar ...

  3. Post irradiation maxillary sinus sarcoma

    International Nuclear Information System (INIS)

    Radiation-induced cancer of the head and neck is well known, but radiation-induced sarcoma is rare. Only nine cases have been reported in the Japanese literature. We treated a patient with post irradiation sarcoma arising in the maxillary sinus. She is now 60 years old and had received radiation therapy for left maxillary carcinoma in 1952. In 1972, left maxillary sarcoma was found and she received postoperative radiation therapy again. Then right nasal carcinoma was found in 1980, and she again received postoperative radiation therapy. Then left maxillary sarcoma was found in 1992. There have been no previous reports of three consecutive radiation-induced malignancies developing in a patient. (author)

  4. Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer.

    Science.gov (United States)

    Rao, Chinthalapally V; Janakiram, Naveena B; Madka, Venkateshwar; Kumar, Gaurav; Scott, Edgar J; Pathuri, Gopal; Bryant, Taylor; Kutche, Hannah; Zhang, Yuting; Biddick, Laura; Gali, Hariprasad; Zhao, Yan D; Lightfoot, Stan; Mohammed, Altaf

    2016-04-01

    Pancreatic cancer is an aggressive neoplasm with almost uniform lethality and a 5-year survival rate of 7%. Several overexpressed mucins that impede drug delivery to pancreatic tumors have been therapeutically targeted, but enzymes involved in mucin biosynthesis have yet to be preclinically evaluated as potential targets. We used survival data from human patients with pancreatic cancer, next-generation sequencing of genetically engineered Kras-driven mouse pancreatic tumors and human pancreatic cancer cells to identify the novel core mucin-synthesizing enzyme GCNT3 (core 2 β-1,6 N-acetylglucosaminyltransferase). In mouse pancreatic cancer tumors, GCNT3 upregulation (103-fold; P pancreatic cancer cells reduced proliferation and spheroid formation. Using in silico small molecular docking simulation approaches, we identified talniflumate as a novel inhibitor that selectively binds to GCNT3. In particular, docking predictions suggested that three notable hydrogen bonds between talniflumate and GCNT3 contribute to a docking affinity of -8.3 kcal/mol. Furthermore, talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro Collectively, our findings suggest that targeting mucin biosynthesis through GCNT3 may improve drug responsiveness, warranting further development and investigation in preclinical models of pancreatic tumorigenesis. Cancer Res; 76(7); 1965-74. ©2016 AACR. PMID:26880801

  5. Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-05-01

    Full Text Available Hsian-Yu Wang,1,2 Min-Kung Hsu,3,4 Kai-Hsuan Wang,1 Ching-Ping Tseng,2,4 Feng-Chi Chen,3,4 John T-A Hsu1,4 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU, Hsinchu, 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 4Department of Biological Sc