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Sample records for cancer post gefitinib

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

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    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......B receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative...... to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, -6.1-9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status...

  2. The therapy of gefitinib towards breast cancer partially through ...

    African Journals Online (AJOL)

    Abstract. Background: Breast cancer remains the leading reason of cancer death among women worldwide, and gefitinib is the effi- cient drug for breast cancer. Aims: To use targeted metabolomics method to elucidate the therapeutic mechanism of gefitinib through profiling the amino acids. Methods: Healthy women (n=56) ...

  3. Ten Years of Complete Remission of Pulmonary Metastasis after Post-Cystectomy Palliative Cisplatin-Gemcitabine Chemotherapy with Gefitinib for Muscle Invasive Bladder Cancer: A Case Report.

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    Fahmy, Omar; Scharpf, Marcus; Schubert, Tina; Feyerabend, Susan; Stenzl, Arnulf; Schwentner, Christian; Fend, Falko; Gakis, Georgios

    2016-01-01

    Muscle-invasive bladder cancer (MIBC) is considered one of the most lethal malignancies with high metastatic potential. Usually, metastatic bladder cancer carries worse prognosis with a median survival rate of approximately 6 months, which can be prolonged for up to 14 months with palliative systemic chemotherapy. We present the case of a 61-year-old male patient diagnosed with localized MIBC 10 years ago. He underwent nerve-sparing radical cystectomy with ileal neobladder, but developed pulmonary metastatic disease 7 months postoperatively. Six cycles of gemcitabine/cisplatin combination chemotherapy with an addition of gefitinib as daily oral medication were administered within a randomized phase II clinical trial; this resulted in complete remission of the pulmonary metastases. Until now, the patient is still on gefitinib daily without any side effects. Although, the addition of gefitinib to standard systemic chemotherapy has not been shown to improve the survival in metastatic urothelial cancer, this case represents a very pleasant albeit uncommon long-term outcome. © 2016 S. Karger AG, Basel.

  4. 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

    with indication of changed ER phenotype (based on collected pathology reports) were immunohistochemically reassessed centrally. 115 patients were eligible for this study; 59 patients in the gefitinib group and 56 patients in the placebo group. Five (4.3%) of 115 tumors changed ER phenotype from negative...

  5. Gefitinib in advanced non-small cell lung cancer: does it deserve a second chance?

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    Stinchcombe, Thomas E; Socinski, Mark A

    2008-09-01

    There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m(2) every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC.

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

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    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.

  7. 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. ...

  8. 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, Mogens; Ingvar, Christian; Jörgensen, Leif

    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...

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

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    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. Gefitinib versus docetaxel in treated non-small-cell lung cancer: a meta-analysis

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    Wang Bing

    2017-06-01

    Full Text Available The objective of this study was to perform a meta-analysis to evaluate the efficacy and toxicity of gefitinib and docetaxel in treated patients with non-small-cell lung cancer (NSCLC. Methods. A literature search was performed using PubMed and CNKI databases for relevant keywords and the Medical Subject Headings. After further full-text screening, 10 clinical trials were included in the final meta-analysis. Specific odds ratios (OR and confidence intervals were calculated. Results. The outcomes of treatment efficacy included disease control rates, quality-of-life improvement rates, 3~4 grade adverse events. Comparing gefitinib to docetaxel for NSCLC patients, the pooled odds ratios (OR of disease control rates was 1.09, (95% confidential index [CI] = 0.84–1.43, the pooled OR of quality-of-life improvement rates was 2.49, (95% CI = 1.77–3.49, the pooled OR of 3~4 grade adverse events was 0.49, (95% CI = 0.32–0.75. Conclusion. Gefitinib was found to significantly improve patients’ quality-of-life and obviously decrease patients’ adverse events of 3~4 grade.There is no difference of disease control rates between gefitinib and docetaxel.

  11. Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

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    Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

    2018-06-01

    Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

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    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  13. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

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    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  14. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

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    Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

    2006-11-01

    A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

  15. Pharmacokinetics of Gefitinib in a Patient with Non-Small Cell Lung Cancer Undergoing Continuous Ambulatory Peritoneal Dialysis

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    Teppei Yamaguchi

    2015-02-01

    Full Text Available A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD for chronic renal failure and who had undergone right upper lobectomy for lung adenocarcinoma (pT2aN0M0 2 years ago was admitted for recurrence of lung cancer presenting as multiple brain metastases. An epidermal growth factor receptor mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746-A750 in exon 19. After whole-brain radiotherapy, we started daily administration of 250 mg gefitinib under the continuation of CAPD and performed a pharmacokinetic analysis. We speculated that the plasma concentration of gefitinib reached the steady state at least by day 16 after the start of gefitinib (626.6 ng/ml at trough level. On day 46, the plasma concentration was 538.4 ng/ml at trough level and the concentration in the peritoneal dialysis fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the pharmacokinetics of gefitinib. During gefitinib therapy, there were no significant adverse events except for grade 2 diarrhea. Gefitinib could be safely administered to a patient undergoing CAPD.

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

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    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. AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations

    International Nuclear Information System (INIS)

    Zhao, Ren; Zhou, Shun; Xia, Bing; Zhang, Cui-ying; Hai, Ping; Zhe, Hong; Wang, Yan-yang

    2016-01-01

    Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the standard care of patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), development of acquired resistance is inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. Strategies or agents to overcome this type of resistance are still limited. In this study, enhanced antitumor effect of AT-101, a-pan-Bcl-2 inhibitor, on gefitinib was explored in NSCLC with T790M mutation. The effect of cotreatment with AT-101 and gefitinib on the viability of NSCLC cell lines harboring acquired T790M mutation was investigated using the MTT assay. The cellular apoptosis of NSCLC cells after cotreatment with AT-101 and gefitinib was assessed by FITC-annexin V/PI assay and Western blots analysis. The potential underlying mechanisms of the enhanced therapeutic effect for AT-101 was also studied using Western blots analysis. The in vivo anti-cancer efficacy of the combination with AT-101 and gefitinib was examined in a mouse xenograft model. In this study, we found that treatment with AT-101 in combination with gefitinib significantly inhibited cell proliferation, as well as promoted apoptosis of EGFR TKIs resistant lung cancer cells. The apoptotic effects of the use of AT-101 was related to the blocking of antiapoptotic protein: Bcl-2, Bcl-xl, and Mcl-1 and downregrulation of the molecules in EGFR pathway. The observed enhancements of tumor growth suppression in xenografts supported the reverse effect of AT-101 in NSCLC with T790M mutation, which has been found in in vitro studies before. AT-101 enhances gefitinib sensitivity in NSCLC with EGFR T790M mutations. The addition of AT-101 to gefitinib is a promising strategy to overcome EGFR TKIs resistance in NSCLC with EGFR T790M mutations

  18. Molecular Modeling, Docking, Dynamics and simulation of Gefitinib and its derivatives with EGFR in Non-Small Cell Lung Cancer.

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    Reddy, Pulakuntla Swetha; Lokhande, Kiran Bharat; Nagar, Shuchi; Reddy, Vaddi Damodara; Murthy, P Sushma; Swamy, K Venkateswara

    2018-02-27

    Gefitinib (lressa) is the most prescribed drug, highly effective to treat of non-small cell lung cancer; primarily it was considered targeted therapy is a kinase inhibitor. The non-small cell lung cancer caused by the mutation in the Epithelial Growth Factor Receptor (EGFR) gene, Iressa works by blocking the EGFR protein that helps the cancer cell growth. EGFR protein has lead to the development of anticancer therapeutics directed against EGFR inhibitor including Gefitinib for non-small cell lung cancer. To explore research on Gefitinib and its derivatives interaction with crystal structure EGFR to understand the better molecular insights interaction strategies. Molecular modeling of ligands (Gefitinib and its derivatives) was carried out by Avogadro software till atomic angle stable confirmation obtained. The partial charges for the ligands were assigned as per standard protocol for molecular docking. All docking simulations were performed with AutoDockVina. Virtual screening carried out based on binding energy and hydrogen bonding affinity. Molecular dynamics (MD) and Simulation EGFR was done using GROMACS 5.1.1 software to explore the interaction stability in a cell. The stable conformation for EGFR protein trajectories were captured at various time intervals 0-20ns. Few compounds screen based on high affinity as the inhibitor for EGFR may inhibit the cell cycle signalling in non-small cell lung cancer. These result suggested that a computer aided screening approach of a Gefitinib derivatives compounds with regard to their binding to EGFR for identifying novel drugs for the treatment of non-small cell lung cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. 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)

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

    2005-01-01

    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

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

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    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.

  1. Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Colquhoun, AJ; Mchugh, LA; Tulchinsky, E.; Kriajevska, M.; Mellon, JK

    2007-01-01

    External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p=0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p=0.04). Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial. (author)

  2. Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

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    Maurel, Joan; Martin-Richard, Marta; Conill, Carlos; Sanchez, Marcelo; Petriz, Lourdes; Gines, Angels; Miquel, Rosa; Gallego, Rosa; Cajal, Rosana; Ayuso, Carmen; Navarro, Salvador; Marmol, Maribel; Nadal, Cristina; Auge, Josep Maria; Fernandez-Cruz, Laureano; Gascon, Pere

    2006-01-01

    Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm 3 of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m 2 /day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC

  3. Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer.

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    Chen, Su-Yu; Chang, Chao-Lin; Chen, Teng-Hai; Chang, Ya-Wen; Lin, Shwu-Bin

    2016-10-01

    Three pentacyclic triterpene dilactones were isolated from the fruiting bodies of Ganoderma colossum, a medicinal mushroom. Colossolactone H (colo H) as a new compound and the most cytotoxic among the isolates was studied for its anticancer mechanism and the potential use in cancer therapy. Gene expression profiling analysis indicated that treatment of lung cancer cells with colo H caused upregulation of 252 genes and downregulation of 398 genes. Gene ontology enrichment analysis indicated that the downregulated genes were the most significantly enriched in cell cycle progression, and the upregulated genes were significantly enriched in metabolic process, cellular response to stimulus, and oxidation reduction. Accordingly, colo H was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. These events facilitate additive cytotoxicity of colo H and gefitinib for gefitinib-resistant H1650 lung cancer cells. Furthermore, combination of colo H and gefitinib effectively inhibited the growth of tumor xenografts in athymic mice. In addition to the efficacy in adjunctive cancer therapy, we have also demonstrated the isolation of colo H from cultivated G. colossum. Thus it is feasible to use colo H or Ganoderma colossum for cancer therapy. Copyright © 2016. Published by Elsevier B.V.

  4. Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status.

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    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

    2009-05-01

    To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status. 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. 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. 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.

  5. 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

  6. 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)

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J.

    2014-01-01

    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 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

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

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    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.

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

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    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.

  9. Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer.

    Science.gov (United States)

    Bogdanowicz, Brian S; Hoch, Matthew A; Hartranft, Megan E

    2017-04-01

    Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

  10. Epithelial membrane protein-1 is a biomarker of gefitinib resistance.

    Science.gov (United States)

    Jain, Anjali; Tindell, Charles A; Laux, Isett; Hunter, Jacob B; Curran, John; Galkin, Anna; Afar, Daniel E; Aronson, Nina; Shak, Steven; Natale, Ronald B; Agus, David B

    2005-08-16

    We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved for patients with advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit in patients, and, recently, heterozygous somatic mutations within the EGFR catalytic domain have been identified as a clinical correlate to objective response to gefitinib. However, clinical resistance to gefitinib limits the utility of this therapeutic to a fraction of patients, and objective clinical responses are rare. We aimed to assess the molecular phenotype and mechanism of in vivo gefitinib resistance in xenograft models and in patient samples. We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This report suggests the role of the adhesion molecule, EMP-1, as a biomarker of gefitinib clinical resistance, and further suggests a probable cross-talk between this molecule and the EGFR signaling pathway.

  11. The role of BIM-EL and BCL2-α on the efficacy of erlotinib and gefitinib in lung cancer.

    Science.gov (United States)

    Simasi, Jacinta; Oelkrug, Christopher; Schubert, Andreas; Nieber, Karen; Gillissen, Adrian

    2015-04-01

    Tyrosine kinase inhibitors (TKI), erlotinib and gefitinib are small molecule inhibitors which are used for the treatment of lung cancer. But, the development of drug resistance has been reported as one of the major setbacks in oncology. This study focused on the mechanisms leading to secondary resistance by assessing the gene expression of BCL2 family proteins which are associated with the intrinsic apoptotic signaling pathway. 8 genes were investigated in erlotinib and gefitinib treated cells by real time PCR and protein analysis by western blotting. The cells were exposed to the test drugs 48h prior to RNA or protein isolation. It was observed that BIM-EL, a pro-apoptotic protein was up-regulated in cells sensitive to the drugs but not in the resistant cells. On the other hand BCL2-α, an anti-apoptotic protein was up-regulated in the resistant cells and not in the sensitive cells. BCL2-α revealed a counter-regulation effect on BIM-EL and this effect is probably one of the causes of secondary resistance to erlotinib and gefitinib. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. 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)

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

    2013-01-01

    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

  13. 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)

    Watanabe, Satoshi; Miyabayashi, Takao; Narita, Ichiei; Yoshizawa, Hirohisa; Tanaka, Junta; Ota, Takeshi; Kondo, Rie; Tanaka, Hiroshi; Kagamu, Hiroshi; Ichikawa, Kosuke; Koshio, Jun; Baba, Junko

    2011-01-01

    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 2 nd 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 2 nd 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 2 nd 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 2 nd EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2 nd EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy. Our results indicate that a 2 nd EGFR-TKI treatment can be an effective treatment option for gefitinib responders

  14. 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.

  15. 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.

  16. Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

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    Maria Antonietta Gambacorta

    2018-03-01

    Full Text Available Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT in locally advanced rectal cancer (LARC. Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6–8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC, Metastasis Free Survival (MFS, Disease Free Survival (DFS, Disease Specific Survival (DSS and Overall Survival (OS. Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4. Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F. With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2% and gastrointestinal toxicities (10,2%. Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients. Keywords: Rectal cancer, Gefitinib, Log term follow-up, Chemoradiotherapy

  17. Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study.

    Science.gov (United States)

    Crinò, Lucio; Cappuzzo, Federico; Zatloukal, Petr; Reck, Martin; Pesek, Milos; Thompson, Joyce C; Ford, Hugo E R; Hirsch, Fred R; Varella-Garcia, Marileila; Ghiorghiu, Serban; Duffield, Emma L; Armour, Alison A; Speake, Georgina; Cullen, Michael

    2008-09-10

    This phase II, open-label, parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients (age >or= 70 years) were randomly assigned to gefitinib (250 mg/d orally) or vinorelbine (30 mg/m(2) infusion on days 1 and 8 of a 21-day cycle). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and tolerability. Exploratory end points included epidermal growth factor receptor (EGFR) gene copy number by fluorescent in situ hybridization (FISH). Patients were randomly assigned to gefitinib (n = 97) or to vinorelbine (n = 99). Hazard ratios (HR; gefitinib v vinorelbine) were 1.19 (95% CI, 0.85 to 1.65) for PFS and 0.98 (95% CI, 0.66 to 1.47) for OS. ORR and disease control rates were 3.1% (95% CI, 0.6 to 8.8) and 43.3% (for gefitinib) and 5.1% (95% CI, 1.7 to 11.4) and 53.5% (for vinorelbine), respectively. Overall QOL improvement and PSI rates were 24.3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine), respectively. In the 54 patients who were EGFR FISH-positive, HRs were 3.13 (95% CI, 1.45 to 6.76) for PFS and 2.88 (95% CI, 1.21 to 6.83) for OS. There were fewer treatment-related grade 3 to 5 adverse events with gefitinib (12.8%) than with vinorelbine (41.7%). There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib. Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib; this unexpected finding requires further study.

  18. Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.

    Science.gov (United States)

    Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong

    2017-02-21

    Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.

  19. Optimization of gefitinib analogues with potent anticancer activity.

    Science.gov (United States)

    Yin, Kai-Hao; Hsieh, Yi-Han; Sulake, Rohidas S; Wang, Su-Pei; Chao, Jui-I; Chen, Chinpiao

    2014-11-15

    The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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    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.

  1. Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zeng

    Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

  2. Histologic transformation from adenocarcinoma to both small cell lung cancer and squamous cell carcinoma after treatment with gefitinib: A case report.

    Science.gov (United States)

    Yao, Yufeng; Zhu, Zhouyu; Wu, Yimin; Chai, Ying

    2018-05-01

    In the past decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment had been an important therapy for treating advanced EGFR-mutated lung cancer patients. However, a large number of these patients with EGFR-TKIs treatment always acquired resistance to these drugs in one year. The histologic transformation is an important resistance mechanism. Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib. A case of EGFR-mutated lung cancer. Medical thoracoscopy examination was performed and the patient was diagnosed as a EGFR-mutated lung adenocarcinoma. Then gefitinib was administered orally at a dose of 250 mg daily. The patient received treatment with chemotherapy (etoposide 0.1 g day 2-5 +  cis-platinum 30 mg day 2-4) after acquiring resistance to gefitinib. The patient died in April 2017 that survived for 32 months from lung cancer was found for the first time. To the best of our knowledge, it is the first case of EGFR-mutated lung adenocarcinoma transforming to both SCLC and SCC which was treated with and responded to gefitinib.

  3. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.

    Science.gov (United States)

    Shi, Yuankai; Zhang, Li; Liu, Xiaoqing; Zhou, Caicun; Zhang, Li; Zhang, Shucai; Wang, Dong; Li, Qiang; Qin, Shukui; Hu, Chunhong; Zhang, Yiping; Chen, Jianhua; Cheng, Ying; Feng, Jifeng; Zhang, Helong; Song, Yong; Wu, Yi-Long; Xu, Nong; Zhou, Jianying; Luo, Rongcheng; Bai, Chunxue; Jin, Yening; Liu, Wenchao; Wei, Zhaohui; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Dai, Hong; Jiao, Shunchang; Wang, Jie; Liang, Li; Zhang, Weimin; Sun, Yan

    2013-09-01

    Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug

  4. Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of cyclin G-associated kinase and induction of miR-630.

    Directory of Open Access Journals (Sweden)

    Minami A Sakurai

    Full Text Available Cyclin G-associated kinase (GAK, a key player in clathrin-mediated membrane trafficking, is overexpressed in various cancer cells. Here, we report that GAK expression is positively correlated with the Gleason score in surgical specimens from prostate cancer patients. Embryonic fibroblasts from knockout mice expressing a kinase-dead (KD form of GAK showed constitutive hyper-phosphorylation of the epidermal growth factor receptor (EGFR. In addition to the well-known EGFR inhibitors gefitinib and erlotinib, the dietary flavonoid luteolin was a potent inhibitor of the Ser/Thr kinase activity of GAK in vitro. Co-administration of luteolin and gefitinib to PC-3 cells had a greater effect on cell viability than administration of either compound alone; this decrease in viability was associated with drastic down-regulation of GAK protein expression. A comprehensive microRNA array analysis revealed increased expression of miR-630 and miR-5703 following treatment of PC-3 cells with luteolin and/or gefitinib, and exogenous overexpression of miR-630 caused growth arrest of these cells. GAK appears to be essential for cell death because co-administration of gefitinib and luteolin to EGFR-deficient U2OS osteosarcoma cells also had a greater effect on cell viability than administration of either compound alone. Taken together, these findings suggest that GAK may be a new therapeutic target for prostate cancer and osteosarcoma.

  5. Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

    Science.gov (United States)

    Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

    2015-07-01

    Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence

  6. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  7. Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis.

    Science.gov (United States)

    Liu, Yuanyuan; Zhang, Yu; Feng, Gangling; Niu, Qiang; Xu, Shangzhi; Yan, Yizhong; Li, Shugang; Jing, Mingxia

    2017-11-01

    The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1-3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75-0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36-0.55; Panalysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18-2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib

  8. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Science.gov (United States)

    Liang, Wenhua; Wu, Xuan; Fang, Wenfeng; Zhao, Yuanyuan; Yang, Yunpeng; Hu, Zhihuang; Xue, Cong; Zhang, Jing; Zhang, Jianwei; Ma, Yuxiang; Zhou, Ting; Yan, Yue; Hou, Xue; Qin, Tao; Dinglin, Xiaoxiao; Tian, Ying; Huang, Peiyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR), progression free survival (PFS), overall survival (OS) were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs) based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, Picotinib (19%, 29%, NA, NA), respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.

  9. Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature.

    Science.gov (United States)

    Singh, Navneet; Jindal, Aditya; Behera, Digambar

    2014-12-10

    Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

  10. 17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

    Science.gov (United States)

    Girgert, Rainer; Emons, Günter; Gründker, Carsten

    2017-02-01

    Triple-negative breast cancers (TNBCs) are neither susceptible to endocrine therapy due to a lack of estrogen receptor α expression nor trastuzumab. TNBCs frequently overexpress epidermal growth factor receptor (EGFR) and membrane bound estrogen receptor, GPER. To a certain extent the growth of TNBCs is stimulated by 17β-estradiol via GPER. We analyzed whether inhibition of EGFR by gefitinib reduces the expression of GPER and subsequent signal transduction in TNBC cells. Dependence of proliferation on 17β-estradiol was determined using Alamar Blue assay. Expression of GPR30 and activation of c-src, EGFR and cAMP-responsive element binding (CREB) protein by 17β-estradiol was analyzed by western blotting. Expression of c-fos, cyclin D1 and aromatase was determined using RT-PCR. Gefitinib reduced GPER expression concentration‑ and time‑dependently. In HCC70 cells, GPER expression was reduced to 15±11% (p<0.05) after treatment with 200 nM gefitinib for four days, and in HCC1806 cells GPER expression was reduced to 39±5% (p<0.01) of the control. 17β-estradiol significantly increased the percentage of HCC1806 cells within 7 days to 145±29% of the control (HCC70, 110±8%). This increase in cell growth was completely prevented in both TNBC cell lines after GPR30 expression was downregulated by treatment with 200 nM gefitinib. In HCC1806 cells, activation of c-src was increased by 17β-estradiol to 350±50% (p<0.01), and gefitinib reduced src activation to 110%. Similar results were obtained in the HCC70 cells. Phosphorylation of EGFR increased to 240±40% (p<0.05) in the HCC1806 cells treated with 17β-estradiol (HCC70, 147±25%). Gefitinib completely prevented this activation. Phosphorylation of CREB and induction of c-fos, cyclin D1 and aromatase expression by 17β-estradiol were all prevented by gefitinib. These experiments conclusively show that reduction of GPER expression is a promising therapeutic approach for TNBC.

  11. Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer.

    Science.gov (United States)

    Imai, Hisao; Kuwako, Tomohito; Kaira, Kyoichi; Masuda, Tomomi; Miura, Yosuke; Seki, Kaori; Sakurai, Reiko; Utsugi, Mitsuyoshi; Shimizu, Kimihiro; Sunaga, Noriaki; Tomizawa, Yoshio; Ishihara, Shinichi; Ishizuka, Takao; Mogi, Akira; Hisada, Takeshi; Minato, Koichi; Takise, Atsushi; Saito, Ryusei; Yamada, Masanobu

    2017-03-01

    In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m 2 ), normal (18.5-25 kg/m 2 ), and overweight (≥25 kg/m 2 ). The median BSA and BW were 1.48 m 2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups. Gefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.

  12. 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

    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.

  13. 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.

  14. Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Chouaid, Christos; Luciani, Laura; LeLay, Katell; Do, Pascal; Bennouna, Jaafar; Perol, Maurice; Moro-Sibilot, Denis; Vergnenègre, Alain; de Pouvourville, Gérard

    2017-10-01

    The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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

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    Solmi, Rossella [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Montroni, Isacco [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy); Mattei, Gabriella [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Taffurelli, Mario [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy); Santini, Donatella [Dipartimento di Patologia, Università di Bologna, Bologna (Italy); Pezzetti, Furio [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Ruggeri, Alessandro [Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell' Apparato Locomotore, Università di Bologna, Bologna (Italy); Castellani, Gastone [Centro Interdipartimentale L. Galvani, Università di Bologna, Bologna (Italy); DIMORFIPA, Università di Bologna, Bologna (Italy); Guidotti, Lia [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Coppola, Domenico [H. Lee Moffit Cancer Center and Research Institute, University of South Florida, Tampa, FL (United States); Strippoli, Pierluigi; Lauriola, Mattia [Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna (Italy); Francesconi, Mirko [Centro Interdipartimentale L. Galvani, Università di Bologna, Bologna (Italy); DIMORFIPA, Università di Bologna, Bologna (Italy); Martini, Désirée [Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell' Apparato Locomotore, Università di Bologna, Bologna (Italy); Voltattorni, Manuela [Laboratori di Biotecnologie, Via Beverara 123, Bologna (Italy); Ceccarelli, Claudio [Dipartimento di Patologia, Università di Bologna, Bologna (Italy); Ugolini, Giampaolo; Rosati, Giancarlo; Zanotti, Simone [Dipartimento Emergenza/Urgenza, Chirurgia Generale e dei Trapianti, Università di Bologna, Bologna (Italy)

    2008-08-08

    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

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

    Directory of Open Access Journals (Sweden)

    Pezzetti Furio

    2008-08-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion This is the first study to have systematically investigated

  17. 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)

    Solmi, Rossella; Montroni, Isacco; Mattei, Gabriella; Taffurelli, Mario; Santini, Donatella; Pezzetti, Furio; Ruggeri, Alessandro; Castellani, Gastone; Guidotti, Lia; Coppola, Domenico; Strippoli, Pierluigi; Lauriola, Mattia; Francesconi, Mirko; Martini, Désirée; Voltattorni, Manuela; Ceccarelli, Claudio; Ugolini, Giampaolo; Rosati, Giancarlo; Zanotti, Simone

    2008-01-01

    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

  18. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

    Science.gov (United States)

    Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

    2018-04-01

    The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

  19. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  20. Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma.

    Science.gov (United States)

    Jeannot, Victor; Busser, Benoit; Vanwonterghem, Laetitia; Michallet, Sophie; Ferroudj, Sana; Cokol, Murat; Coll, Jean-Luc; Ozturk, Mehmet; Hurbin, Amandine

    2016-01-01

    Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated. The effects of the synergistic drug combinations were also studied in human lung adenocarcinoma and hepatocarcinoma cells in vivo. The combination of gefitinib and vorinostat synergistically reduced cell growth and strongly induced apoptosis through inhibition of the insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT)-dependent signaling pathway. Moreover, the gefitinib and vorinostat combination strongly inhibited tumor growth in mice with lung adenocarcinoma or hepatocarcinoma tumor xenografts. In contrast, the combination of sorafenib and vorinostat did not inhibit cell proliferation compared to a single treatment and induced G 2 /M cell cycle arrest without apoptosis. The sorafenib and vorinostat combination sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent signaling pathways. These results showed that there was synergistic cytotoxicity when vorinostat was combined with gefitinib for both lung adenocarcinoma and hepatocarcinoma with mutant KRAS in vitro and in vivo but that the combination of vorinostat with sorafenib did not show any benefit. These findings highlight the important role of the IGF-1R/AKT pathway in the resistance to targeted therapies and support the use of histone deacetylase inhibitors in combination with EGFR-tyrosine kinase inhibitors, especially for

  1. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

    Science.gov (United States)

    Hegedüs, Csilla; Truta-Feles, Krisztina; Antalffy, Géza; Várady, György; Német, Katalin; Ozvegy-Laczka, Csilla; Kéri, György; Orfi, László; Szakács, Gergely; Settleman, Jeffrey; Váradi, András; Sarkadi, Balázs

    2012-08-01

    Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Phenethyl Isothiocyanate Induces Apoptotic Cell Death Through the Mitochondria-dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.

    Science.gov (United States)

    Hsia, Te-Chun; Huang, Yi-Ping; Jiang, Yi-Wen; Chen, Hsin-Yu; Cheng, Zheng-Yu; Hsiao, Yung-Ting; Chen, Cheng-Yen; Peng, Shu-Fen; Chueh, Fu-Shin; Chou, Yu-Cheng; Chung, Jing-Gung

    2018-04-01

    Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro. The total cell viability, apoptotic cell death, production of reactive oxygen species (ROS) and Ca 2+ , levels of mitochondria membrane potential (ΔΨ m ) and caspase-3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced chromatin condensation was examined by DAPI staining. PEITC-induced cell morphological changes, decreased total viable cell number and induced apoptotic cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased Ca 2+ production, decreased the levels of ΔΨ m and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was used to examine the effect of apoptotic cell death associated protein expression in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro-apoptotic protein Bax in NCI-H460/G cells. Based on these results, we suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria-dependent pathway in NCI-H460/G cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Directory of Open Access Journals (Sweden)

    Wenhua Liang

    Full Text Available Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons.We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR, progression free survival (PFS, overall survival (OS were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs based on Bayesian network integrated the efficacy and specific toxicities of all included treatments.Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001 through direct meta-analysis. In the network meta-analyses, no statistically significant differences in efficacy were found between these four TKIs with respect to all outcome measures. Trend analyses of rank probabilities revealed that the cumulative probabilities of being the most efficacious treatments were (ORR, 1-year PFS, 1-year OS, 2-year OS: erlotinib (51%, 38%, 14%, 19%, gefitinib (1%, 6%, 5%, 16%, afatinib (29%, 27%, 30%, 27% and icotinib (19%, 29%, NA, NA, respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib.The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed

  4. Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma

    Directory of Open Access Journals (Sweden)

    Jeannot V

    2016-11-01

    Full Text Available Victor Jeannot,1,2 Benoit Busser,1–3 Laetitia Vanwonterghem,1,2 Sophie Michallet,1,2 Sana Ferroudj,1,2 Murat Cokol,4 Jean-Luc Coll,1,2 Mehmet Ozturk,1,2,5 Amandine Hurbin1,2 1INSERM U1209, Department Cancer Targets and Experimental Therapeutics, Grenoble, France; 2University Grenoble Alpes, Institute for Advanced Biosciences, Grenoble, France; 3Department of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, Grenoble, France; 4Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey; 5Faculty of Medicine, Dokuz Eyul University, Izmir Biomedicine and Genome Center, Izmir, Turkey Abstract: Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR-tyrosine kinase inhibitor (gefitinib or a multi-targeted kinase inhibitor (sorafenib in combination with a histone deacetylase inhibitor (vorinostat on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated. The effects of the synergistic drug combinations were also studied in human lung adenocarcinoma and hepatocarcinoma cells in vivo. The combination of gefitinib and vorinostat synergistically reduced cell growth and strongly induced apoptosis through inhibition of the insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT-dependent signaling pathway. Moreover, the gefitinib and vorinostat combination strongly inhibited tumor growth in mice with lung adenocarcinoma or hepatocarcinoma tumor xenografts. In contrast, the combination of sorafenib and vorinostat did not inhibit cell proliferation compared to a single treatment and induced G2/M cell cycle arrest without

  5. 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

    randomly assigned with dynamic balancing to receive gefitinib (250 mg per day orally; n=733) or docetaxel (75 mg/m(2) intravenously in 1-h infusion every 3 weeks; n=733). The primary objective was to compare overall survival between the groups with co-primary analyses to assess non...

  6. Cost-effectiveness analysis of EGFR mutation testing and gefitinib as first-line therapy for non-small cell lung cancer.

    Science.gov (United States)

    Narita, Yusuke; Matsushima, Yukiko; Shiroiwa, Takeru; Chiba, Koji; Nakanishi, Yoichi; Kurokawa, Tatsuo; Urushihara, Hisashi

    2015-10-01

    The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JP¥122,000 (US$1180; US$1=JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin-paclitaxel for the treatment for NSCLC in Japan. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence.

    Science.gov (United States)

    Segovia-Mendoza, Mariana; González-González, María E; Barrera, David; Díaz, Lorenza; García-Becerra, Rocío

    2015-01-01

    An increasing number of tumors, including breast cancer, overexpress proteins of the epidermal growth factor receptor (EGFR) family. The interaction between family members activates signaling pathways that promote tumor progression and resistance to treatment. Human epidermal growth factor receptor type II (HER2) positive breast cancer represents a clinical challenge for current therapy. It has motivated the development of novel and more effective therapeutic EGFR family target drugs, such as tyrosine kinase inhibitors (TKIs). This review focuses on the effects of three TKIs mostly studied in HER2- positive breast cancer, lapatinib, gefitinib and neratinib. Herein, we discuss the mechanism of action, therapeutic advantages and clinical applications of these TKIs. To date, TKIs seem to be promising therapeutic agents for the treatment of HER2-overexpressing breast tumors, either as monotherapy or combined with other pharmacological agents.

  8. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

    Science.gov (United States)

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-02-07

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

  9. 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.

  10. Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chi-Chen [Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan (China); Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan (China); Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan (China); Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan (China); Chen, Jing-Ting [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lin, Meng-Wei [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chan, Chia-Hao [Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan (China); Wen, Yueh-Feng [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan (China); Wu, Shin-Bei [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chung, Ting-Wen [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lyu, Kevin W. [Lutheran Medical Center, Brooklyn, NY (United States); Global Scholars Program, St. George' s University/Northumbria University, Newcastle upon Tyne (United Kingdom); Chou, Hsiu-Chuan, E-mail: chouhc@mail.nhcue.edu.tw [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); and others

    2015-11-01

    Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

  11. Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

    International Nuclear Information System (INIS)

    Lin, Chi-Chen; Chen, Jing-Ting; Lin, Meng-Wei; Chan, Chia-Hao; Wen, Yueh-Feng; Wu, Shin-Bei; Chung, Ting-Wen; Lyu, Kevin W.; Chou, Hsiu-Chuan

    2015-01-01

    Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

  12. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial.

    Science.gov (United States)

    Paz-Ares, L; Tan, E-H; O'Byrne, K; Zhang, L; Hirsh, V; Boyer, M; Yang, J C-H; Mok, T; Lee, K H; Lu, S; Shi, Y; Lee, D H; Laskin, J; Kim, D-W; Laurie, S A; Kölbeck, K; Fan, J; Dodd, N; Märten, A; Park, K

    2017-02-01

    In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases. Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. NCT01466660. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  13. The Efficacy and Toxicity of Gefitinib in Treating Non-small Cell Lung Cancer: A Meta-analysis of 19 Randomized Clinical Trials

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    Wo, Hongmei; He, Jing; Zhao, Yang; Yu, Hao; Chen, Feng; Yi, Honggang

    2018-01-01

    Background: This meta-analysis evaluated the efficacy and toxicity of gefitinib with other commonly used drugs in different treatment settings and epidermal growth factor receptor (EGFR) mutation status. Methods: Nineteen randomize clinical trials (RCTs) of 6,554 patients with NSCLC were pooled in this meta-analysis by random-effects or fixed-effects model, whichever is proper. Results: In first-line therapy, gefitinib showed higher odds than chemotherapy (OR = 2.19, 95% CI: 1.20-4.01), but less than other targeted therapies (OR = 0.58, 95% CI: 0.38-0.88). As non-first-line therapy, the overall survival (OS) and progression-free survival (PFS) were similar between gefitinib and controls (HR = 1.00, 95% CI: 0.93-1.08; HR = 0.91, 95% CI: 0.72-1.15), respectively. With the regard to toxicity, the incidences of dry skin, rash and pruritus were higher in gefitinib compared with controls, while gefitinib significantly reduced the incidence of hematologic toxicity. Conclusion: Gefitinib might be more efficient than chemotherapy, but less efficient than other targeted therapies in ORR, especially in EGFR mutation-positive patients. Gefitinib can decrease the odds of hematologic toxicity compared to controls. Future studies, especially those with EGFR mutation-positive patients, will be needed to confirm our findings. PMID:29721056

  14. Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

    Science.gov (United States)

    Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

    2017-09-01

    This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

  15. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

    2008-03-01

    Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

  16. Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics.

    Directory of Open Access Journals (Sweden)

    Mark S Cragg

    2007-10-01

    Full Text Available The epidermal growth factor receptor (EGFR plays a critical role in the control of cellular proliferation, differentiation, and survival. Abnormalities in EGF-EGFR signaling, such as mutations that render the EGFR hyperactive or cause overexpression of the wild-type receptor, have been found in a broad range of cancers, including carcinomas of the lung, breast, and colon. EGFR inhibitors such as gefitinib have proven successful in the treatment of certain cancers, particularly non-small cell lung cancers (NSCLCs harboring activating mutations within the EGFR gene, but the molecular mechanisms leading to tumor regression remain unknown. Therefore, we wished to delineate these mechanisms.We performed biochemical and genetic studies to investigate the mechanisms by which inhibitors of EGFR tyrosine kinase activity, such as gefitinib, inhibit the growth of human NSCLCs. We found that gefitinib triggered intrinsic (also called "mitochondrial" apoptosis signaling, involving the activation of BAX and mitochondrial release of cytochrome c, ultimately unleashing the caspase cascade. Gefitinib caused a rapid increase in the level of the proapoptotic BH3-only protein BIM (also called BCL2-like 11 through both transcriptional and post-translational mechanisms. Experiments with pharmacological inhibitors indicated that blockade of MEK-ERK1/2 (mitogen-activated protein kinase kinase-extracellular signal-regulated protein kinase 1/2 signaling, but not blockade of PI3K (phosphatidylinositol 3-kinase, JNK (c-Jun N-terminal kinase or mitogen-activated protein kinase 8, or AKT (protein kinase B, was critical for BIM activation. Using RNA interference, we demonstrated that BIM is essential for gefitinib-induced killing of NSCLC cells. Moreover, we found that gefitinib-induced apoptosis is enhanced by addition of the BH3 mimetic ABT-737.Inhibitors of the EGFR tyrosine kinase have proven useful in the therapy of certain cancers, in particular NSCLCs possessing

  17. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

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    Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

    2009-09-03

    Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for

  18. Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1

    Directory of Open Access Journals (Sweden)

    Nakahara Y

    2016-08-01

    Full Text Available Yoshiro Nakahara,1,2 Yusuke Takagi,1,3 Yukio Hosomi,1 Akiko Kagei,4 Tomohiro Yamamoto,4 Takeshi Sawada,5 Makiko Yomota,1 Yusuke Okuma,1 Shinichiro Mikura,1,6 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 2Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, 3Oncology Scientific Affairs, Merck Sharp & Dohme Corp, 4GeneticLab Co., Ltd., Sapporo, 5Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 6Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Japan Background: Repetitive genotyping is useful to assess the genetic evolution of non-small-cell lung cancer (NSCLC during treatment, but the need for sampling by biopsy is a major obstacle. Digital polymerase chain reaction (PCR is a promising procedure for the detection of mutant alleles in plasma of cancer patients.Methods: This prospective study enrolled patients with NSCLC and known epidermal growth factor receptor (EGFR mutations and who had experienced disease progression during ongoing EGFR-tyrosine kinase inhibitor (TKI therapy. Eligible patients received daily gefitinib and either pemetrexed or S-1 every 3 weeks until disease progression or the development of unacceptable toxicity. Peripheral blood was collected before and after the combination therapy for digital PCR and hepatocyte growth factor measurement.Results: From May 2012 to January 2014, nine patients with a median age of 67 (range 52–80 years were enrolled. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance, observed in seven patients, and primary resistance, observed in two patients. Known EGFR mutations were detected in plasma samples of six (67% patients at study enrollment. Of these, T790M mutation was concurrently detected in three (50% patients

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

    International Nuclear Information System (INIS)

    Ryu, Yon Ju; Chun, Eun Mi; Lee, Soon Nam; Shim, Sung Shin

    2014-01-01

    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.

  20. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).

    Science.gov (United States)

    Fukuoka, Masahiro; Wu, Yi-Long; Thongprasert, Sumitra; Sunpaweravong, Patrapim; Leong, Swan-Swan; Sriuranpong, Virote; Chao, Tsu-Yi; Nakagawa, Kazuhiko; Chu, Da-Tong; Saijo, Nagahiro; Duffield, Emma L; Rukazenkov, Yuri; Speake, Georgina; Jiang, Haiyi; Armour, Alison A; To, Ka-Fai; Yang, James Chih-Hsin; Mok, Tony S K

    2011-07-20

    The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR

  1. Gefitinib upregulates death receptor 5 expression to mediate rmhTRAIL-induced apoptosis in Gefitinib-sensitive NSCLC cell line

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    Yan D

    2015-07-01

    Full Text Available Dong Yan,1,2 Yang Ge,1 Haiteng Deng,3 Wenming Chen,4 Guangyu An1 1Department of Oncology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Translational Molecular pathology, M.D Anderson Cancer Center, Houston, TX, USA; 3School of Sciences, Tsinghua University, 4Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL triggers apoptosis in tumor cells, but when used alone, it is not effective in the treatment of TRAIL-resistant tumors. Some studies have shown that gefitinib interacts with recombinant mutant human TRAIL (rmhTRAIL to induce high levels of apoptosis in gefitinib-responsive bladder cancer cell lines; however, the molecular mechanisms underlying the anticancer effects are not fully understood. Several reports have shown that the death receptor 5 (DR5 plays an important role in sensitizing cancer cells to apoptosis induced by TRAIL. Therefore, we investigated the effects of the combination of drugs and the expression of the DR5 to analyze the growth of a gefitinib-responsive non-small cell lung cancer cell line PC9, which was treated with rmhTRAIL and gefitinib individually or in combination.Methods: Human PC9 non-small cell lung cancer cells harboring an epidermal growth factor receptor mutation were used as a model for the identification of the therapeutic effects of gefitinib alone or in combination with rmhTRAIL, and cytotoxicity was assessed by MTT assays. Cell cycle and apoptosis were investigated using flow cytometry. Moreover, the effects of drugs on DR5, BAX, FLIP, and cleaved-caspase3 proteins expressions were analyzed using Western blot analyses. Finally, quantitative polymerase chain reaction analysis was carried out to assess whether rmhTRAIL and gefitinib modulate the expression of genes related to drug activity.Results: Gefitinib and rmh

  2. Ileal perforation induced by acute radiation injury under gefitinib treatment

    International Nuclear Information System (INIS)

    Muraoka, Takayuki; Tsukuda, Kazunori; Toyooka, Shinichi

    2011-01-01

    Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR. (author)

  3. Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines.

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    Maricla Galetti

    Full Text Available BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism.The present study, performed in a panel of NSCLC cell lines expressing different ABCG2 plasma membrane levels, was designed to investigate the effect of the efflux transporter ABCG2 on intracellular gefitinib accumulation, by dissecting the contribution of uptake and efflux processes.Our findings indicate that gefitinib, in lung cancer cells, inhibits ABCG2 activity, as previously reported. In addition, we suggest that ABCG2 silencing or overexpression affects intracellular gefitinib content by modulating the uptake rather than the efflux. Similarly, overexpression of ABCG2 affected the expression of a number of drug transporters, altering the functional activities of nutrient and drug transport systems, in particular inhibiting MPP, glucose and glutamine uptake.Therefore, we conclude that gefitinib is an inhibitor but not a substrate for ABCG2 and that ABCG2 overexpression may modulate the expression and activity of other transporters involved in the uptake of different substrates into the cells.

  4. 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

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    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

  5. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  6. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Science.gov (United States)

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

  7. The gefitinib long-term responder (LTR)--a cancer stem-like cell story? Insights from molecular analyses of German long-term responders treated in the IRESSA expanded access program (EAP).

    Science.gov (United States)

    Gottschling, Sandra; Herpel, Esther; Eberhardt, Wilfried E E; Heigener, David F; Fischer, Jürgen R; Köhne, Claus-Henning; Kortsik, Cornelius; Kuhnt, Thomas; Muley, Thomas; Meister, Michael; Bischoff, Helge G; Klein, Peter; Moldenhauer, Ines; Schnabel, Philipp A; Thomas, Michael; Penzel, Roland

    2012-07-01

    In selected patients with advanced non-small cell lung cancer (NSCLC) the EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor (TKI) gefitinib (IRESSA) shows response rates of ≥ 70% and a significant prolongation of progression free survival (PFS). However, cogent biomarkers predicting long-term response to EGFR-TKIs are yet lacking. Cancer stem-like cells (CSC) are thought to play a pivotal role in tumor regeneration and appear to be influenced by the EGFR-pathway. This makes them a promising candidate for predicting long-term response to EGFR-TKIs. We analyzed pre-therapeutic tissue specimens of a rare and specific subset of previously treated German patients with advanced NSCLC who experienced ≥ 3 year response to gefitinib within the International IRESSA EAP. 11/20 identified long-term responders (LTRs) had appropriate tissue specimens available. Those were analyzed for EGFR and k-ras (Kirsten rat sarcoma) mutations, EGFR and c-met (met proto-oncogene) amplifications and protein expression of EGFR, E-cadherin/vimentin and the CSC antigens CD133 and BCRP1 (breast cancer resistance protein 1). The results were compared to primary resistant patients (RPs) and intermediate responders (IRs) showing a median response of 8.6 months. Each group consisted of 6 women and 5 men, with 1 squamous cell carcinoma (SCC) and 10 adenocarcinoma (AC). Along the LTRs, all but the SCC had EGFR mutations, whereas the RPs had no EGFR, but k-ras mutations in 5/11 cases. 8/11 IRs had EGFR and 3/11 k-ras mutations, of which 2 occurred concomitantly. One patient of each group had an EGFR and/or c-met amplification. EGFR and E-cadherin/vimentin expression was not different between the groups, whereas CD133 was expressed only in 4/10 LTRs and BCRP1 predominantly in responders. The LTRs showed a substantially longer mean PFS to previous therapies, a substantially lower number of metastatic sites and almost exclusively pulmonary or pleural metastasis. LTRs display established

  8. Gefitinib

    Science.gov (United States)

    ... of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance ... blisters or peeling skin swelling of the eyes, face, lips, tongue, throat, hands, arms, feet, ankles or ...

  9. Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel.

    Science.gov (United States)

    Arrieta, Oscar; Anaya, Pablo; Morales-Oyarvide, Vicente; Ramírez-Tirado, Laura Alejandra; Polanco, Ana C

    2016-09-01

    Assess the cost-effectiveness of an EGFR-mutation testing strategy for advanced NSCLC in first-line therapy with either gefitinib or carboplatin-paclitaxel in Mexican institutions. Cost-effectiveness analysis using a discrete event simulation (DES) model to simulate two therapeutic strategies in patients with advanced NSCLC. Strategy one included patients tested for EGFR-mutation and therapy given accordingly. Strategy two included chemotherapy for all patients without testing. All results are presented in 2014 US dollars. The analysis was made with data from the Mexican frequency of EGFR-mutation. A univariate sensitivity analysis was conducted on EGFR prevalence. Progression-free survival (PFS) transition probabilities were estimated on data from the IPASS and simulated with a Weibull distribution, run with parallel trials to calculate a probabilistic sensitivity analysis. PFS of patients in the testing strategy was 6.76 months (95 % CI 6.10-7.44) vs 5.85 months (95 % CI 5.43-6.29) in the non-testing group. The one-way sensitivity analysis showed that PFS has a direct relationship with EGFR-mutation prevalence, while the ICER and testing cost have an inverse relationship with EGFR-mutation prevalence. The probabilistic sensitivity analysis showed that all iterations had incremental costs and incremental PFS for strategy 1 in comparison with strategy 2. There is a direct relationship between the ICER and the cost of EGFR testing, with an inverse relationship with the prevalence of EGFR-mutation. When prevalence is >10 % ICER remains constant. This study could impact Mexican and Latin American health policies regarding mutation detection testing and treatment for advanced NSCLC.

  10. 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)

    Van Waes, Carter; Allen, Clint T.; Citrin, Deborah; Gius, David; Colevas, A. Dimetrios; Harold, Nancy A.; Rudy, Susan; Nottingham, Liesl; Muir, Christine; Chen, Zhong; Singh, Anurag K.; Dancey, Janet; Morris, John C.

    2010-01-01

    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/m 2 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.

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

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Wang, Meihua; Robins, H. Ian; Lautenschlaeger, Tim; Curran, Walter J.; Brachman, David G.; Schultz, Christopher J.; Choucair, Ali; Dolled-Filhart, Marisa; Christiansen, Jason; Gustavson, Mark; Molinaro, Annette; Mischel, Paul; Dicker, Adam P.

    2013-01-01

    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

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

    International Nuclear Information System (INIS)

    Yamashita, Yoshiko; Aoki, Takatoshi; Korogi, Yukunori; Hanagiri, Takeshi; Uramoto, Hidetaka; Yoshii, Chiharu; Mukae, Hiroshi

    2012-01-01

    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.)

  13. 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.)

  14. Content analysis of cancer blog posts.

    Science.gov (United States)

    Kim, Sujin

    2009-10-01

    The efficacy of user-defined subject tagging and software-generated subject tagging for describing and organizing cancer blog contents was explored. The Technorati search engine was used to search the blogosphere for cancer blog postings generated during a two-month period. Postings were mined for relevant subject concepts, and blogger-defined tags and Text Analysis Portal for Research (TAPoR) software-defined tags were generated for each message. Descriptive data were collected, and the blogger-defined tags were compared with software-generated tags. Three standard vocabularies (Opinion Templates, Basic Resource, and Medical Subject Headings [MeSH] Resource) were used to assign subject terms to the blogs, with results compared for efficacy in information retrieval. Descriptive data showed that most of the studied cancer blogs (80%) contained fewer than 500 words each. The numbers of blogger-defined tags per posting (M = 4.49 per posting) were significantly smaller than the TAPoR keywords (M = 23.55 per posting). Both blogger-defined subject tags and software-generated subject tags were often overly broad or overly narrow in focus, producing less than effective search results for those seeking to extract information from cancer blogs. Additional exploration into methods for systematically organizing cancer blog postings is necessary if blogs are to become stable and efficacious information resources for cancer patients, friends, families, or providers.

  15. 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

  16. 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.

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

    International Nuclear Information System (INIS)

    Chang, Cheng-Yi; Kuan, Yu-Hsiang; Ou, Yen-Chuan; Li, Jian-Ri; Wu, Chih-Cheng; Pan, Pin-Ho; Chen, Wen-Ying; Huang, Hsuan-Yi; Chen, Chun-Jung

    2014-01-01

    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

  18. Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

    Science.gov (United States)

    Lu, Yan; Liu, Pengyuan; Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; Wen, Weidong; Grubbs, Clinton J; Lubet, Ronald A; You, Ming

    2012-02-01

    The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10(-8) and r = 0.73, P = 1.50 × 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell

  19. Incidental cancer in multinodular goitre post thyroidectomy

    African Journals Online (AJOL)

    of choice to rule out cancer in patients presenting with MNG is fine- ... Method. Records of patients who underwent thyroidectomy between January 2005 and December 2010 at Chris Hani .... each of benign goitre and atypical cells, one Hurthle cell lesion .... 6%) in their retrospective audit of MNG post thyroidectomy. The.

  20. 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)

    Zhao, Songji; Kuge, Yuji; Zhao, Yan; Takeuchi, Satoshi; Hirata, Kenji; Takei, Toshiki; Shiga, Tohru; Dosaka-Akita, Hirotoshi; Tamaki, Nagara

    2013-01-01

    The purpose of this study was to evaluate whether early changes in 3′-deoxy-3′- 3 H-fluorothymidine ( 3 H-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 3 H-FLT and 18 F-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 3 H-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 18 F-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

  1. Functional cooperation between HIF-1α and c-Jun in mediating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR.

    Science.gov (United States)

    Meng, Shuyan; Wang, Guorui; Lu, Yang; Fan, Zhen

    2018-07-01

    Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are important transcription factors regulating expression of genes involved in cell survival. HIF-1α and c-Jun are key components of HIF-1 and AP-1, respectively, and are regulated by epidermal growth factor receptor (EGFR)-mediated cell signaling and tumor microenvironmental cues. The roles of HIF-1α and c-Jun in development of resistance to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) with activating mutation of EGFR have not been explored. In this study, we investigated the roles of HIF-1α and c-Jun in mediating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR. Changes in HIF-1α protein and in total and phosphorylated c-Jun levels in relation to changes in total and phosphorylated EGFR levels before and after gefitinib treatment were measured using Western blot analysis in NSCLC cells sensitive or resistant to gefitinib. The impact of overexpression of a constitutively expressed HIF-1α (HIF-1α/ΔODD) or a constitutively active c-Jun upstream regulator (SEK1 S220E/T224D mutant) on cell response to gefitinib was also examined. The effect of pharmacological inhibition of SEK1-JNK-c-Jun pathway on cell response to gefitinib was evaluated. Downregulation of HIF-1α and total and phosphorylated c-Jun levels correlated with cell inhibitory response to gefitinib better than decrease in phosphorylated EGFR did in NSCLC cells with intrinsic or acquired resistance to gefitinib. Overexpression of HIF-1α/ΔODD or SEK1 S220E/T224D mutant conferred resistance to gefitinib. There exists a positive feed-forward regulation loop between HIF-1 and c-Jun. The JNK inhibitor SP600125 sensitized gefitinib-resistant NSCLC cells to gefitinib. HIF-1α and c-Jun functionally cooperate in development of resistance to gefitinib in NSCLC cells. The translational value of inhibiting HIF-1α/c-Jun cooperation in overcoming resistance to EGFR TKI

  2. Screening for breast cancer post reduction mammoplasty

    International Nuclear Information System (INIS)

    Muir, T.M.; Tresham, J.; Fritschi, L.; Wylie, E.

    2010-01-01

    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.

  3. Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib

    Directory of Open Access Journals (Sweden)

    Tomohisa Fukui

    2017-06-01

    Full Text Available Alopecia associated with epidermal growth factor receptor (EGFR inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.

  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. Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.

    Directory of Open Access Journals (Sweden)

    Hiroe Tabara

    Full Text Available Gefitinib (Iressa is an inhibitor of the epidermal growth factor receptor (EGFR that has shown promising activity in the treatment of patients with non-small cell lung cancer (NSCLC. However, adverse side effects of gefitinib treatment, such as respiratory dysfunction, have limited the therapeutic benefit of this targeting strategy. The present results show that this adverse effect can be attributed to the inhibition of the novel gefitinib target GAK (Cyclin G-associated kinase, which is as potently inhibited by the drug as the tyrosine kinase activity of EGFR. Knockout mice expressing the kinase-dead form of GAK (GAK-kd died within 30 min after birth primarily due to respiratory dysfunction. Immunohistochemical analysis revealed that surfactant protein A (SP-A was abundant within alveolar spaces in GAK-kd(+/+ mice but not in GAK-kd(-/- pups. E-cadherin and phosphorylated EGFR signals were also abnormal, suggesting the presence of flat alveolar cells with thin junctions. These results suggest that inhibition of GAK by gefitinib may cause pulmonary alveolar dysfunction, and the present study may help prevent side effects associated with gefitinib therapy in NSCLC patients.

  6. Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR

    International Nuclear Information System (INIS)

    Choi, Yoon Ji; Lee, Dae Ho; Choi, Chang Min; Lee, Jung Shin; Lee, Seung Jin; Ahn, Jin-Hee; Kim, Sang-We

    2015-01-01

    Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR. Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0—2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m 2 , and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile. A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0–57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0–55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm. PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR. The study is registered with ClinicalTrials.gov (NCT01196234). Registration date is 08/09/2010

  7. A quality by design approach on polymeric nanocarrier delivery of gefitinib: formulation, in vitro, and in vivo characterization

    Directory of Open Access Journals (Sweden)

    Kola Srinivas NS

    2016-12-01

    of gefitinib. Keywords: gefitinib, cancer, epidermal growth factor receptor tyrosine kinase receptors inhibitor, bioavailability, Eudragit® RL100, PVP K30, PVA, Biopharmaceutical Classification System class II, QbD, design of experiment, full factorial design

  8. 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...

  9. Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet.

    Science.gov (United States)

    Quinn, Edel M; Corrigan, Mark A; McHugh, Seamus M; Murphy, David; O'Mullane, John; Hill, Arnold D; Redmond, Henry Paul

    2013-02-01

    Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. Breast related topics had significantly more posts per day compared to others (mean 66.7, p Anonymous posts were common (55%) and less likely to be accurate (p internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. PET-CT imaging with [18F]-gefitinib to measure Abcb1a/1b (P-gp) and Abcg2 (Bcrp1) mediated drug–drug interactions at the murine blood–brain barrier

    International Nuclear Information System (INIS)

    Vlaming, Maria L.H.; Läppchen, Tilman; Jansen, Harm T.; Kivits, Suzanne; Driel, Andy van; Steeg, Evita van de; Hoorn, José W. van der; Sio, Charles F.; Steinbach, Oliver C.; DeGroot, Jeroen

    2015-01-01

    Introduction: The efflux transporters P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are expressed at the blood–brain barrier (BBB), and can limit the access of a wide range of drugs to the brain. In this study we developed a PET-CT imaging method for non-invasive, quantitative analysis of the effect of ABCB1 and ABCG2 on brain penetration of the anti-cancer drug gefitinib, and demonstrated the applicability of this method for identification and quantification of potential modulators of ABCB1 and ABCB2 using the dual inhibitor elacridar. Methods: In vitro cellular accumulation studies with [ 14 C]-gefitinib were conducted in LLC-PK1, MDCKII, and the corresponding ABCB1/Abcb1a and ABCG2/Abcg2 overexpressing cell lines. Subsequently, in vivo brain penetration of [ 18 F]-gefitinib was quantified by PET-CT imaging studies in wild-type, Abcg2 −/− , Abcb1a/1b −/− , and Abcb1a/1b;Abcg2 −/− mice. Results: In vitro studies showed that [ 14 C]-gefitinib is a substrate of the human ABCB1 and ABCG2 transporters. After i.v. administration of [ 18 F]-gefitinib (1 mg/kg), PET-CT imaging showed 2.3-fold increased brain levels of [ 18 F]-gefitinib in Abcb1a/1b;Abcg2 −/− mice, compared to wild-type. Levels in single knockout animals were not different from wild-type, showing that Abcb1a/1b and Abcg2 together limit access of [ 18 F]-gefitinib to the brain. Furthermore, enhanced brain accumulation of [ 18 F]-gefitinib after administration of the ABCB1 and ABCG2 inhibitor elacridar (10 mg/kg) could be quantified with PET-CT imaging. Conclusions: PET-CT imaging with [ 18 F]-gefitinib is a powerful tool to non-invasively assess potential ABCB1- and ABCG2-mediated drug–drug interactions (DDIs) in vivo. Advances in knowledge and implications for patient care: This minimally-invasive, [ 18 F]-based PET-CT imaging method shows the interplay of ABCB1 and ABCG2 at the BBB in vivo. The method may be applied in the future to assess ABCB1 and

  11. Prediction of sensitivity to gefitinib/erlotinib for EGFR mutations in NSCLC based on structural interaction fingerprints and multilinear principal component analysis.

    Science.gov (United States)

    Zou, Bin; Lee, Victor H F; Yan, Hong

    2018-03-07

    Non-small cell lung cancer (NSCLC) with activating EGFR mutations, especially exon 19 deletions and the L858R point mutation, is particularly responsive to gefitinib and erlotinib. However, the sensitivity varies for less common and rare EGFR mutations. There are various explanations for the low sensitivity of EGFR exon 20 insertions and the exon 20 T790 M point mutation to gefitinib/erlotinib. However, few studies discuss, from a structural perspective, why less common mutations, like G719X and L861Q, have moderate sensitivity to gefitinib/erlotinib. To decode the drug sensitivity/selectivity of EGFR mutants, it is important to analyze the interaction between EGFR mutants and EGFR inhibitors. In this paper, the 30 most common EGFR mutants were selected and the technique of protein-ligand interaction fingerprint (IFP) was applied to analyze and compare the binding modes of EGFR mutant-gefitinib/erlotinib complexes. Molecular dynamics simulations were employed to obtain the dynamic trajectory and a matrix of IFPs for each EGFR mutant-inhibitor complex. Multilinear Principal Component Analysis (MPCA) was applied for dimensionality reduction and feature selection. The selected features were further analyzed for use as a drug sensitivity predictor. The results showed that the accuracy of prediction of drug sensitivity was very high for both gefitinib and erlotinib. Targeted Projection Pursuit (TPP) was used to show that the data points can be easily separated based on their sensitivities to gefetinib/erlotinib. We can conclude that the IFP features of EGFR mutant-TKI complexes and the MPCA-based tensor object feature extraction are useful to predict the drug sensitivity of EGFR mutants. The findings provide new insights for studying and predicting drug resistance/sensitivity of EGFR mutations in NSCLC and can be beneficial to the design of future targeted therapies and innovative drug discovery.

  12. Targeting post-translational modifications of histones for cancer therapy.

    Science.gov (United States)

    Hsu, Y-C; Hsieh, Y-H; Liao, C-C; Chong, L-W; Lee, C-Y; Yu, Y-L; Chou, R-H

    2015-10-30

    Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Abdominal drainage versus no drainage post gastrectomy for gastric cancer.

    Science.gov (United States)

    Wang, Zhen; Chen, Junqiang; Su, Ka; Dong, Zhiyong

    2011-08-10

    Gastrectomy remains the primary therapeutic method for resectable gastric cancer. Thought of as an important measure to reduce post-operative complications and mortality, abdominal drainage was used widely after gastrectomy for gastric cancer in previous decades. The benefits of abdominal drainage have been questioned by researchers in recent years. The objectives of this review were to access the benefits and harms of routine abdominal drainage post gastrectomy for gastric cancer. We searched the Cochrane Controlled Trials Register (Central/CCTR) in The Cochrane Library (2010, Issue 10), including the Specialised Registers of the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group; MEDLINE (via Pubmed, 1950 to October, 2010); EMBASE (1980 to October, 2010); and the Chinese National Knowledge Infrastructure (CNKI) Database (1979 to October, 2010). We included randomised controlled trials (RCTs) comparing abdominal drain versus no drain in patients who had undergone gastrectomy (not considering the scale of gastrectomy and the extent of lymphadenectomy; irrespective of language, publication status, and the type of drain). We excluded RCTs comparing one drain with another. From each trial, we extracted the data on the methodological quality and characteristics of the included studies, mortality (30-day mortality), re-operations, post-operative complications (pneumonia, wound infection, intra-abdominal abscess, anastomotic leak, drain-related complications), operation time, length of post-operative hospital stay and initiation of soft diet. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence intervals (CI). For continuous data, we calculated mean differences (MD) and 95% CI. We tested heterogeneity using the Chi(2) test. We used a fixed-effect model for data analysis with RevMan software but we used a random-effects model if the P value of the Chi(2) test was less than 0.1. We included four RCTs involving 438 patients (220

  19. Post-treatment problems of African American breast cancer survivors.

    Science.gov (United States)

    Barsevick, Andrea M; Leader, Amy; Bradley, Patricia K; Avery, Tiffany; Dean, Lorraine T; DiCarlo, Melissa; Hegarty, Sarah E

    2016-12-01

    African American breast cancer survivors (AABCS) have a lower survival rate across all disease stages (79 %) compared with White survivors (92 %) and often have more aggressive forms of breast cancer requiring multimodality treatment, so they could experience a larger burden of post-treatment quality of life (QOL) problems. This paper reports a comprehensive assessment of the number, severity, and domains of problems faced by AABCS within 5 years after treatment completion and identifies subgroups at risk for these problems. A population-based random sample was obtained from the Pennsylvania Cancer Registry of African American females over 18 years of age who completed primary treatment for breast cancer in the past 5 years. A mailed survey was used to document survivorship problems. Two hundred ninety-seven AABCS completed the survey. The median number of survivor problems reported was 15. Exploratory factor analysis of the problem scale revealed four domains: emotional problems, physical problems, lack of resources, and sexuality problems. Across problem domains, younger age, more comorbid conditions, and greater medical mistrust were risk factors for more severe problems. The results demonstrated that AABCS experienced significant problem burden in the early years after diagnosis and treatment. In addition to emotional and physical problem domains that were documented in previous research, two problem domains unique to AABCS included lack of resources and sexuality concerns. At risk groups should be targeted for intervention. The study results reported in this manuscript will inform future research to address problems of AABCS as they make the transition from cancer patient to cancer survivor.

  20. The therapy of gefitinib towards breast cancer partially through ...

    African Journals Online (AJOL)

    Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/ahs.v15i2.36 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of ...

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

    Science.gov (United States)

    Cancer-related post-traumatic stress can occur any time from diagnosis to after treatment ends. Shock, fear, helplessness, or horror can be felt by cancer patients and lead to cancer-related post-traumatic stress. Learn about the causes and ways doctors can help manage these symptoms of distress in this expert-reviewed summary.

  2. Sexual functioning among early post-treatment breast cancer survivors.

    Science.gov (United States)

    Avis, Nancy E; Johnson, Aimee; Canzona, Mollie Rose; Levine, Beverly J

    2018-02-17

    This study aims (1) to estimate percentages of partnered women who are sexually active over the first 2 years post-breast cancer diagnosis; (2) to identify factors related to sexual inactivity; and (3) to evaluate separately, among both sexually active and inactive survivors, the relation between sexual problems and treatment-related variables, symptoms, and psychosocial factors. Longitudinal observational study of breast cancer survivors recruited within 8 months of cancer diagnosis and followed for 18 months. The main outcome measures were (1) being sexually active/inactive in the past month and (2) sexual problems assessed with the four-item sexual problem domain of the Quality of Life in Adult Cancer Survivors (QLACS) scale. At baseline, 52.4% of women reported being sexually active in the past month. This percentage increased to 60.7% 18 months later. In multivariable repeated-measures analyses, age, past chemotherapy, depressive symptoms, and lower perceived attractiveness were related to inactivity. Sexually inactive women reported more problems on the QLACS than sexually active women. In stratified multivariable analyses, depressive symptoms were related to greater sexual problems for both sexually active and inactive women, as was vaginal dryness. Among the sexually active women, younger age at diagnosis, less illness intrusiveness, and lower perceived attractiveness were related to more problems. Research has shown that sexual functioning/sexual health are key aspects of quality of life for many cancer survivors, and are often not addressed by health care providers. Future studies should examine how such topics are handled by clinicians in their interactions with survivors.

  3. Efficacy of post-operative radiotherapy in the treatment of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Api, P; Corcione, S; Magnoni, G

    1985-01-01

    A clinical evaluation regarding the efficacy of post-operative radiotherapy in 294 patients with breast cancer is presented. In the author's opinion post-operative radiotherapy is fundamental in the treatment of this tumor. 21 refs.

  4. Combination therapy with gefitinib and doxorubicin inhibits tumor growth in transgenic mice with adrenal neuroblastoma

    International Nuclear Information System (INIS)

    Kawano, Kumi; Hattori, Yoshiyuki; Iwakura, Hiroshi; Akamizu, Takashi; Maitani, Yoshie

    2013-01-01

    Highly relevant mouse models of human neuroblastoma (NB) are needed to evaluate new therapeutic strategies against NB. In this study, we characterized transgenic mice with bilateral adrenal tumors. On the basis of information from the tumoral gene expression profiles, we examined the antitumor effects of unencapsulated and liposomal doxorubicin (DXR), alone and in combination with gefitinib, on adrenal NB. We showed that intravenous injection of unencapsulated or liposomal DXR alone inhibited tumor growth in a dose-dependent manner, as assessed by magnetic resonance imaging (MRI). However, liposomal DXR did not exhibit greater antitumor effect than unencapsulated DXR. Immunohistochemical analysis revealed that the adrenal tumor vasculature with abundant pericyte coverage was a less leaky structure for liposomes. Combination therapy with unencapsulated or liposomal DXR plus gefitinib strongly suppressed tumor growth and delayed tumor regrowth than treatment with unencapsulated or liposomal DXR alone, even at a lower dose of DXR. Dynamic contrast-enhanced MRI analysis revealed that gefitinib treatment increased blood flow in the tumor, indicating that gefitinib treatment changes the tumor vascular environment in a manner that may increase the antitumor effect of DXR. In conclusion, the combination of gefitinib and DXR induces growth inhibition of adrenal NBs in transgenic mice. These findings will provide helpful insights into new treatments for NB

  5. Fluorescent polymer-based post-translational differentiation and subtyping of breast cancer cells.

    Science.gov (United States)

    Scott, Michael D; Dutta, Rinku; Haldar, Manas K; Wagh, Anil; Gustad, Thomas R; Law, Benedict; Friesner, Daniel L; Mallik, Sanku

    2012-12-07

    Herein, we report the application of synthesized fluorescent, water soluble polymers for post-translational subtyping and differentiation of breast cancer cells in vitro. The fluorescence emission spectra from these polymers were modulated differently in the presence of conditioned cell culture media from various breast cancer cells. These polymers differentiate at a post-translation level possibly due to their ability to interact with extracellular enzymes that are over-expressed in cancerous conditions.

  6. Effectiveness of transcutaneous electrical nerve stimulation on saliva production in post-radiated oral cancer patients

    OpenAIRE

    Sakshi Ojha; Thimmarasa V Bhovi; Prashant P Jaju; Manas Gupta; Neha Singh; Kriti Shrivastava

    2016-01-01

    Aims and Objectives: To determine the effectiveness of transcutaneous electrical nerve stimulation (TENS) in stimulating salivary flow in post-radiated oral cancer patients, and to compare the salivary flow rate between unstimulated saliva and saliva stimulated with TENS in post-radiated oral cancer patients. Materials and Methods: In 30 patients who underwent radiotherapy for oral cancer, unstimulated saliva was collected every minute for 5 min in a graduated test tube. The TENS unit was act...

  7. CT measurement of fat in pre- and post-menopausal women with breast cancer

    International Nuclear Information System (INIS)

    Sato, Masanori; Ogura, Toshihiro

    2011-01-01

    Since breast cancer is the most common cancer among Japanese women, research leading to its prevention and early detection is important, and many studies have reported a relationship between this cancer and obesity. In addition, it has been reported that the risk of breast cancer posed by obesity differs between pre- and post-menopausal patients. In this study, we investigated the difference in the amount of body fat between pre- and post-menopausal breast cancer patients by measuring the areas of total, visceral, and subcutaneous fat on CT images acquired at the level of the umbilicus. The subjects were 136 women, comprising 63 with breast cancer (21 pre- and 42 post-menopausal) and 73 with other diseases (31 pre- and 42 post menopausal). We found that post-menopausal women with breast cancer had a significantly greater amount of fat than their pre-menopausal counterparts, presumably attributable to the action of estrogen. These results suggest that fat accumulation in post-menopausal women increases the risk of breast cancer. (author)

  8. The role of post-traumatic stress and post-traumatic growth on online information use in breast cancer survivors.

    Science.gov (United States)

    Casellas-Grau, A; Sumalla, E C; Lleras, M; Vives, J; Sirgo, A; León, C; Rodríguez, A; Campos, G; Valverde, Y; Borràs, J M; Ochoa, C

    2018-05-08

    Changes perceived as both positive (e.g., post-traumatic growth [PTG]) and negative (e.g. post-traumatic stress symptoms [PTSS]) have been associated with intensive internet use among breast cancer survivors. In this multi-center study, we analyzed the role of PTG and PTSS on the amount of time spent looking for online cancer information, its content, and its psychological impact. PTSS and PTG were assessed in 182 breast cancer survivors using the Post-traumatic Stress Disorder Checklist and Post-traumatic Growth Inventory questionnaires. Subjects also completed a questionnaire about their behavior when looking for online illness-related information (i.e., time spent, type of contents, and psychological impact). PTSS positively correlated with the amount of time spent looking for cancer-related information, including both medical and psychosocial content. By contrast, PTG showed no relationships with the amount of time, but with a predominant search for cancer-related psychosocial information. The psychological impact of online information was associated with participants' levels of PTG and/or PTSS. Whereas PTG was related to a decrease of women's hope, PTSS was linked to the perception of being less conscious or inadequately informed about the illness, thereby increasing feelings of distress. PTSS and PTG show relationships with the amount of time spent online, the type of information accessed online, and the psychological impact of internet use. Health professionals should prescribe online information according to the psychological response to cancer. There is a need for professional-led online resources to provide patients with timely information as well as support sites to facilitate psychological adjustment. This article is protected by copyright. All rights reserved.

  9. 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.)

  10. Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

    Science.gov (United States)

    Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

    2016-01-01

    It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

  11. 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.…

  12. Pattern of breast cancer risk factors among pre and post ...

    African Journals Online (AJOL)

    Context: The incidence of breast cancer is increasing worldwide. In black women, breast cancer is associated with aggressive features and poor survival. Objective: Identification of risk factors such as early age of menarche, obesity and family history of breast cancer may permit preventive strategies. Study Design: A ...

  13. [Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy].

    Science.gov (United States)

    Schuette, W; Dietel, M; Thomas, M; Eberhardt, W; Griesinger, F; Zirrgiebel, U; Radke, S; Schirmacher, P

    2016-08-01

    To analyze the influence of the localization of mutations in the epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and overall survival (OS) in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT) under real world conditions within the REASON study. Subgroups of pts with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were analyzed for PFS and OS according to gef or CT treatment and compared using the log-rank test. Pts with mutations in exon 19 and 18/20 treated with gef as first line therapy showed increased PFS and OS compared to CT. This increase was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months), but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was significantly increased in patients with mutation in exon 19 treated with gef ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). Localization and nature of EGFR mutations influences gefitinib treatment outcomes under routine conditions and should therefore be analyzed in detail. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Cancer in an unexpected site post pouch surgery for familial adenomatous polyposis (FAP

    Directory of Open Access Journals (Sweden)

    Omar A. Alwahbi

    2018-01-01

    Conclusion: Although the risk of developing adenomas or carcinomas in the ileal pouch post proctocolectomy with IPAA is low it should not be neglected as cancer occurrence or recurrence is unpredictable even with appropriate measures.

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

    Science.gov (United States)

    Cancer-related post-traumatic stress (PTS) can occur any time from diagnosis until the end of treatment; treatment used in PTSD can be useful in reducing distress. Get comprehensive information on PTS in this summary for clinicians.

  16. Retrospective study of 48 cases of post-operative radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Mnejja, W.; Yahiaoui, S.; Siala, W.; Daoud, J.; Ghorbel, A.; Frikha, M.

    2011-01-01

    The authors report a study which aimed at assessing therapeutic results after post-operative radiotherapy of 48 patients suffering from head and neck cancers. The analysis is made in terms of cancer control, survival without recurrence and global survival. The post-operative radiotherapy improves the disease control rate. Ganglionary attack and capsular failure are survival prognosis factors. The concomitant association of chemo-therapy and radiotherapy should improve therapeutic results. Short communication

  17. The pre, post brachytherapy and postoperative CEA serum concentration of 53 rectal cancer patients

    International Nuclear Information System (INIS)

    Nguyen Thanh Danh; Nguyen Kim Luu; Phan Van Dan

    2008-01-01

    CEA serum concentration level of 53 rectal cancer patients was measured at moments pre, post brachytherapy (45 Gy), post surgery one week, 6 months and 12 months. Response to radiation with reduce CEA serum concentration was achieved in 20/53 patients (37,7%), mainly at staging Dukes B, C. Postoperative CEA level of patients significantly decreased, especially in resection group. (author)

  18. Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS).

    Science.gov (United States)

    Thongprasert, Sumitra; Duffield, Emma; Saijo, Nagahiro; Wu, Yi-Long; Yang, James Chih-Hsin; Chu, Da-Tong; Liao, Meilin; Chen, Yuh-Min; Kuo, Han-Pin; Negoro, Shunichi; Lam, Kwok Chi; Armour, Alison; Magill, Patrick; Fukuoka, Masahiro

    2011-11-01

    Evaluation of health-related quality-of-life (HRQoL) and symptom improvement were preplanned secondary objectives for the overall population and posthoc analyses for epidermal growth factor receptor (EGFR) mutation-positive/negative subgroups in IPASS. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) and Trial Outcome Index (TOI); symptom improvement by the Lung Cancer Subscale (LCS). Improvements defined as: 6 or more (FACT-L; TOI), 2 or more (LCS) points increase maintained for 21 or more days. Overall (n = 1151/1217 evaluable), HRQoL improvement rates were significantly greater with gefitinib versus carboplatin/paclitaxel; symptom improvement rates were similar for both treatments. Significantly more patients recorded improvements in HRQoL and symptoms with gefitinib in the EGFR mutation-positive subgroup (n = 259; FACT-L 70.2% versus 44.5%; odds ratio, 3.01 [95% confidence interval, 1.79-5.07]; p < 0.001; TOI 70.2% versus 38.3%; 3.96 [2.33-6.71]; p < 0.001; LCS 75.6% versus 53.9%; 2.70 [1.58-4.62]; p < 0.001), and with carboplatin/paclitaxel in the EGFR mutation-negative subgroup (n = 169; FACT-L 14.6% versus 36.3%; odds ratio, 0.31 [0.15-0.65]; p = 0.002; TOI 12.4% versus 28.8%; 0.35 [0.16-0.79]; p = 0.011; LCS 20.2% versus 47.5%; 0.28 [0.14-0.55]; p < 0.001). Median time-to-worsening (months) FACT-L score was longer with gefitinib versus carboplatin/paclitaxel for the overall population (8.3 versus 2.5) and EGFR mutation-positive subgroup (15.6 versus 3.0), and similar for both treatments in the EGFR mutation-negative subgroup (1.4 versus 1.4). Median time-to-improvement with gefitinib was 8 days in patients with EGFR mutation-positive tumors who improved. HRQoL and symptom endpoints were consistent with efficacy outcomes in IPASS and favored gefitinib in patients with EGFR mutation-positive tumors and carboplatin/paclitaxel in patients with EGFR mutation-negative tumors.

  19. Role of scintimammography in post surgical management of breast cancer

    International Nuclear Information System (INIS)

    Choudhury, P.S.; Bhatia, S.; Gupta, A.; Sharma, P.K.; Kumar, R.; Pandey, K.K.

    2004-01-01

    Tetrofosmin separately. To summarise, scintimammographic interpretation, being independent of tissue density, will be of use in the post surgical management of breast cancer in detection of both recurrent and residual disease. This can also be used to exclude multifocal / multicentric disease as more and more breast conserving surgery will be the rule rather than an exception, in times to come, in carefully selected cases. (author)

  20. Evaluating Post-Radiotherapy Laryngeal Function with Laryngeal Videostroboscopy in Early Stage Glottic Cancer

    Directory of Open Access Journals (Sweden)

    Ariel E. Marciscano

    2017-06-01

    Full Text Available ObjectiveDysphonia is common among patients with early stage glottic cancer. Laryngeal videostroboscopy (LVS has not been routinely used to assess post-radiotherapy (RT voice changes. We hypothesized that LVS would demonstrate improvement in laryngeal function after definitive RT for early-stage glottic cancer.Study designBlinded retrospective review of perceptual voice and stroboscopic parameters for patients with early glottic cancer and controls.SettingHigh-volume, single-institution academic medical center.Subjects and methodsFifteen patients underwent RT for Tis-T2N0M0 glottic cancer and were evaluated with serial LVS exams pre- and post-RT. Stroboscopic assessment included six parameters: vocal fold (VF vibration, VF mobility, erythema/edema, supraglottic compression, glottic closure, and secretions. Grade, roughness, breathiness, asthenia, strain (GRBAS voice perceptual scale was graded in tandem with LVS score. Assessments were grouped by time interval from RT: pre-RT, 0–4, 4–12, and >12 months post-RT.Results60 LVS exams and corresponding GRBAS assessments were reviewed. There were significant improvements in ipsilateral VF motion (P = 0.03 and vibration (P = 0.001 and significant worsening in contralateral VF motion (P < 0.001 and vibration (P = 0.008 at >12 months post-RT. Glottic closure significantly worsened, most prominent >12 months post-RT (P = 0.01. Composite GRBAS scores were significantly improved across all post-RT intervals.ConclusionLVS proved to be a robust tool for assessing pre- and post-RT laryngeal function. We observed post-RT improvement in ipsilateral VF function, a decline in contralateral VF function, and decreased glottic closure. These results demonstrate that LVS can detect meaningful changes in VF and glottic function and support its use for post-RT evaluation of glottic cancer patients.

  1. Topic Modeling of Smoking- and Cessation-Related Posts to the American Cancer Society's Cancer Survivor Network (CSN): Implications for Cessation Treatment for Cancer Survivors Who Smoke.

    Science.gov (United States)

    Westmaas, J Lee; McDonald, Bennett R; Portier, Kenneth M

    2017-08-01

    Smoking is a risk factor in at least 18 cancers, and approximately two-thirds of cancer survivors continue smoking following diagnosis. Text mining of survivors' online posts related to smoking and quitting could inform strategies to reduce smoking in this vulnerable population. We identified posts containing smoking/cessation-related keywords from the Cancer Survivors Network (CSN), an online cancer survivor community of 166 000 members and over 468 000 posts since inception. Unsupervised topic model analysis of posts since 2000 using Latent Dirichlet Allocation extracted 70 latent topics which two subject experts inspected for themes based on representative terms. Posterior analysis assessed the distribution of topics within posts, and the range of themes discussed across posts. Less than 1% of posts (n = 3998) contained smoking/cessation-related terms, and covered topics related to cancer diagnoses, treatments, and coping. The most frequent smoking-related topics were quit smoking methods (5.4% of posts), and the environment for quitters (2.9% of posts), such as the stigma associated with being a smoker diagnosed with cancer and lack of empathy experienced compared to nonsmokers. Smoking as a risk factor for one's diagnosis was a primary topic in only 1.7% of smoking/cessation-related posts. The low frequency of smoking/cessation-related posts may be due to expected criticism/stigma for smoking but may also suggests a need for health care providers to address smoking and assist with quitting in the diagnostic and treatment process. Topic model analysis revealed potential barriers that should be addressed in devising clinical or population-level interventions for cancer survivors who smoke. Although smoking is a major risk factor for cancer, little is known about cancer patients' or survivors' views or concerns about smoking and quitting. This study used text mining of posts to an online community of cancer patients and survivors to investigate contexts in which

  2. Managing post-therapy fatigue for cancer survivors using energy conservation training.

    Science.gov (United States)

    Yuen, Hon Keung; Mitcham, Maralynne; Morgan, Larissa

    2006-01-01

    This pilot study evaluated the effectiveness of energy conservation training to help post-therapy cancer survivors manage their fatigue. Twelve post-therapy cancer survivors were randomly assigned to an energy conservation training or usual care control (6 in each group). Participants in the intervention group received 1 to 2 hours of individual, face-to-face energy conservation training from an occupational therapist followed by once-a-week telephone monitoring sessions in the subsequent three weeks. Participants in the control group received standard care from their oncologist. Analysis of pre- and post-training data from the Piper Fatigue Scale (PFS) revealed significant reduction only in the sensory subscale of the PFS (Z = 2.21; p = 0.027) for the intervention group; but no significant reduction in the four subscale or total scores of the PFS for the control group. Findings demonstrate partial support for the effectiveness of energy conservation training in helping post-therapy cancer survivors manage their fatigue. Energy conservation training seems to be a viable strategy for managing cancer-related fatigue, though its efficacy is modest. Incorporating specific energy restoration strategies such as relaxation and meditation for future research may help advance the growing body of knowledge in symptom management for post-therapy cancer survivors.

  3. Oncologists' perspectives on post-cancer treatment communication and care coordination with primary care physicians.

    Science.gov (United States)

    Klabunde, C N; Haggstrom, D; Kahn, K L; Gray, S W; Kim, B; Liu, B; Eisenstein, J; Keating, N L

    2017-07-01

    Post-treatment cancer care is often fragmented and of suboptimal quality. We explored factors that may affect cancer survivors' post-treatment care coordination, including oncologists' use of electronic technologies such as e-mail and integrated electronic health records (EHRs) to communicate with primary care physicians (PCPs). We used data from a survey (357 respondents; participation rate 52.9%) conducted in 2012-2013 among medical oncologists caring for patients in a large US study of cancer care delivery and outcomes. Oncologists reported their frequency and mode of communication with PCPs, and role in providing post-treatment care. Seventy-five per cent said that they directly communicated with PCPs about post-treatment status and care recommendations for all/most patients. Among those directly communicating with PCPs, 70% always/usually used written correspondence, while 36% always/usually used integrated EHRs; telephone and e-mail were less used. Eighty per cent reported co-managing with PCPs at least one post-treatment general medical care need. In multivariate-adjusted analyses, neither communication mode nor intensity were associated with co-managing survivors' care. Oncologists' reliance on written correspondence to communicate with PCPs may be a barrier to care coordination. We discuss new research directions for enhancing communication and care coordination between oncologists and PCPs, and to better meet the needs of cancer survivors post-treatment. © 2017 John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Scholten, Ernst T.; Horeweg, Nanda; Koning, Harry J. de; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Mali, Willem P.T.M.; Jong, Pim A. de

    2015-01-01

    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.)

  5. 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.)

  6. Pattern of breast cancer risk factors among pre and post ...

    African Journals Online (AJOL)

    In black women, breast cancer is associated with aggressive features and poor survival. ... are diagnosed annually, with a mortality rate of 15000 per. Pattern of breast ..... (IUCD), injectables and oral contraceptives were the three most frequently .... risk of both ERPR‑positive and ERPR‑negative tumors with each additional ...

  7. Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

    Science.gov (United States)

    Kang, Jieun; Kim, Seon Ok; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

    2018-05-17

    Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

  8. Treatment with Makmiror-Complex for post-radiation infections volvo-vaginitis in cancer patients

    International Nuclear Information System (INIS)

    Borovtsova, T. M.; Krylov, S.V.; Udovichenko, V.I.

    1996-01-01

    The possibility of applying the Makmiror-Complex preparation for treating post-radiation and post-chemiotherapeutical infections volvo-vaginitis in cancer patients is considered. The multicenter clinical studies of the preparation were conducted by treatment of cervicovaginitis and volvo-vaginitis of mixed etiology, caused by the simplest fungus and various types of bacterial flora. The efficiency of the preparation is as follow: 88% of complete recovery; 9% of improvements and only in 3% of cases with no change

  9. 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...

  10. 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.

  11. Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

    Science.gov (United States)

    Corbett, Teresa; Devane, Declan; Walsh, Jane C; Groarke, AnnMarie; McGuire, Brian E

    2015-12-04

    Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. Some evidence has been reported for interventions for fatigue during active treatment. However, to date, there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer. This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database. We will search the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and relevant sources of grey literature. Randomised controlled trials (RCTs) which have evaluated psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, will be included. Two review authors will independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. Most existing evidence on cancer-related fatigue is from those in active cancer treatment. This systematic review and meta-analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment. With the growing need for stage-specific research in cancer, this review seeks to highlight a gap in current practice and to strengthen the evidence base of randomised controlled trials in the area. PROSPERO CRD42014015219.

  12. Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

    Science.gov (United States)

    Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

  13. Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

    Science.gov (United States)

    Jian, Zhi-Hong; Huang, Jing-Yang; Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively. Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

  14. β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.

    Directory of Open Access Journals (Sweden)

    Jennifer A Talarico

    Full Text Available β-adrenergic receptor (βAR-mediated transactivation of epidermal growth factor receptor (EGFR has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib, including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

  15. 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.

  16. 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

  17. Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine.

    Science.gov (United States)

    Pellegrini, Kathryn L; Patil, Dattatraya; Douglas, Kristen J S; Lee, Grace; Wehrmeyer, Kathryn; Torlak, Mersiha; Clark, Jeremy; Cooper, Colin S; Moreno, Carlos S; Sanda, Martin G

    2017-06-01

    The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection. © 2017 Wiley Periodicals, Inc.

  18. 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...

  19. Post-Traumatic Growth and Resilience in Adolescent and Young Adult Cancer Patients: An Overview

    NARCIS (Netherlands)

    Greup, Suzanne R.; Kaal, Suzanne E. J.; Jansen, Rosemarie; Manten-Horst, Eveliene; Thong, Melissa S. Y.; van der Graaf, Winette T. A.; Prins, Judith B.; Husson, Olga

    2018-01-01

    The aim of this study was to provide an overview of the literature on post-traumatic growth (PTG) and resilience among adolescent and young adult (AYA) cancer patients. A literature search in Embase, PsychInfo, PubMed, Web of Science, Cochrane Library, and Cinahl was carried out. Thirteen articles

  20. 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....

  1. Herbal product use by the cancer patients in both the pre and post ...

    African Journals Online (AJOL)

    Conclusion: Analysis of the results indicates that health professionals need to obtain information regarding the use of herbal products by cancer patients during both pre- and post- surgery periods, as well as during chemotherapy. Patients should be provided with information and guidance about the advantages and ...

  2. Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report.

    Science.gov (United States)

    Hatch, M; Ostroumova, E; Brenner, A; Federenko, Z; Gorokh, Y; Zvinchuk, O; Shpak, V; Tereschenko, V; Tronko, M; Mabuchi, K

    2015-06-01

    The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were <18 years of age at the time of the accident. The report is based on standardized incidence ratio (SIR) analysis of 43 non-thyroid cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR=1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Nutritional status, nutrition practices and post-operative complications in patients with gastrointestinal cancer.

    Science.gov (United States)

    Garth, A K; Newsome, C M; Simmance, N; Crowe, T C

    2010-08-01

    Malnutrition and its associated complications are a considerable issue for surgical patients with upper gastrointestinal and colorectal cancer. The present study aimed to determine whether specific perioperative nutritional practices and protocols are associated with improved patient outcomes in this group. Patients admitted for elective upper gastrointestinal or colorectal cancer surgery (n = 95) over a 19-month period underwent a medical history audit assessing weight changes, nutritional intake, biochemistry, post-operative complications and length of stay. A subset of patients (n = 25) underwent nutritional assessment by subjective global assessment prior to surgery in addition to assessment of post-operative medical outcomes, nutritional intake and timing of dietetic intervention. Mean (SD) length of stay for patients was 14.0 (12.2) days, with complication rates at 35%. Length of stay was significantly longer in patients who experienced significant preoperative weight loss compared to those who did not [17.0 (15.8) days versus 10.0 (6.8) days, respectively; P nutritional assessment, 32% were classified as mild-moderately malnourished and 16% severely malnourished. Malnourished patients were hospitalised twice as long as well-nourished patients [15.8 (12.8) days versus 7.6 (3.5) days; P nutrition post surgery was a factor in post-operative outcomes, with a positive correlation with length of stay (r = 0.493; P cancer. Poor nutritional status coupled with delayed and inadequate post-operative nutrition practices are associated with worse clinical outcomes.

  4. Effectiveness of transcutaneous electrical nerve stimulation on saliva production in post-radiated oral cancer patients

    Directory of Open Access Journals (Sweden)

    Sakshi Ojha

    2016-01-01

    Full Text Available Aims and Objectives: To determine the effectiveness of transcutaneous electrical nerve stimulation (TENS in stimulating salivary flow in post-radiated oral cancer patients, and to compare the salivary flow rate between unstimulated saliva and saliva stimulated with TENS in post-radiated oral cancer patients. Materials and Methods: In 30 patients who underwent radiotherapy for oral cancer, unstimulated saliva was collected every minute for 5 min in a graduated test tube. The TENS unit was activated and stimulated saliva was collected for 5 min in a separate graduated test tube, and the flow rate was compared with the unstimulated salivary flow rate. Results: A statistically significant improvement was seen in saliva production during stimulation (P < 0.001. In addition, statistically significant increase in TENS stimulated saliva was observed in patients aged ≥50 years compared to that in patients aged <50 years (P < 0.05. There was no significant difference in salivary flow rate between the two genders in both stimulated and unstimulated conditions, however, statistically significant increase in salivary flow rate was observed in males under stimulated condition (P < 0.01. Conclusion: TENS was highly effective in stimulating the whole salivary flow rate in post-radiated oral cancer patients. It is an effective supportive treatment modality in xerostomia patients caused by radiotherapy in oral cancer patients.

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

    Science.gov (United States)

    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

    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.

  6. 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.

  7. 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......-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between...... exposure and potential confounders. Considering these challenges, we concluded that using the data would not enlighten the discussion about insulin use and cancer risk and only serve to further complicate any understanding. Therefore, we decided to use our experience to illustrate methodological challenges...

  8. [Exploration of the Care Needs of Post-Chemotherapy Lung Cancer Patients and Related Factors].

    Science.gov (United States)

    Chiu, Hui-Ying; Lin, Yu-Hua; Wang, Chin-Chou; Chen, Wan-Yi; Chang, Huang-Chih; Lin, Meng-Chih

    2016-06-01

    Chemotherapy (CT) is the first priority treatment for advanced stage lung cancer. However, symptom distress, impaired ability to conduct daily activities, and post-CT care needs are potential side effects of CT. To explore the factors related to the care needs of post-chemotherapy lung cancer patients. A cross-sectional study was used. One hundred and twenty-one adult patients who had been diagnosed with advanced-stage lung cancer and who had undergone CT using the Platinum and Docetaxel doublet regimen were recruited from a medical center in southern Taiwan. The instruments used included a nursing care needs survey, symptoms distress scale, daily activity interference scale, and patient characteristics datasheet. Participants self-prioritized their emergency management, health consultation, and emotional support activities based on their perceived care needs. The top three post-CT symptoms in terms of severity were: fatigue, appetite change, and sleep disorder. Primary disruptions in daily activities during the post-CT period related to: holding social activities, work, and stair climbing. Significant and positive correlations were found among daily activity interference (r = .30, p needs. The regression model indicated daily activity interference as a predictor of care needs, accounting for 10.7% of the total variance. These results highlight the relationships among care needs, symptom distress, and daily activity interference in post-chemotherapy lung-cancer patients. The present study provides a reference for nursing care to reduce the symptom distress, to enhance the performance of daily activities, and to meet the care needs of lung-cancer patients.

  9. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice.

    Science.gov (United States)

    Abbas, Muhammad; Habib, Murad; Naveed, Muhammad; Karthik, Kumaragurubaran; Dhama, Kuldeep; Shi, Meiqi; Dingding, Chen

    2017-11-01

    Gastric cancer (GC) is one among the major cancer types, causing human deaths and present noticeable heterogeneity. The incidences and mortality rates are higher in males in comparison to females with a male to female ratio of 2.3:1. A lot of studies have revealed out the molecular basis, pathogenesis, invasion and metastasis related findings of gastric stomach cancer. Present review encompasses the salient information on various biomarkers for the early diagnosis, treatment and prognosis of gastric cancer elaborate the clinical importance of serum tumor markers in patients with this cancer as well as checking the growths, together with epigenetic changes and genetic polymorphisms. A deep and rigorous search was carried out in Pub Med/MEDLINE using specific key words; "gastric cancer", with "tumor marker". Our search yielded 4947 important reports about related topic from books and articles that were published before the end of August 2017. Conclusively, Scientists are utilizing high time and resource to salvage this nemesis which is of global importance and cause health burden. Classical and novel biomarkers are important for treatment as well as pre- and post- diagnosis of GC. Major causes for GC are cigarette smoking, infection by Helicobacter pylori, atrophic gastritis, sex/gender, and high salt intake. Early diagnoses of GC is important for the management, treatment, pathological diagnoses by stage prognosis and metastatic setting; although the treatment outcome proved to be not much fruitful following chemotherapy, and oral medication with oxaliplatin, capecitabine, cisplatin and 5- fluorouracil (5-FU). More research studies and exploring the practical usage of gastric cancer biomarkers in diagnosis, prognosis and pre- and post- chemotherapy in clinical practice for countering gastric cancers would alleviate to some extent the ill health sufferings of humans being caused by this important and common cancerous condition. Copyright © 2017 Elsevier Masson SAS

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

    Directory of Open Access Journals (Sweden)

    Stefano Occhipinti

    Full Text Available 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.

  11. Post-treatment fertility in patients with testicular cancer

    International Nuclear Information System (INIS)

    Fossaa, S.D.; Aabyholm, T.; Normann, N.; Jetne, V.

    1986-01-01

    Sperm analysis and serum hormone measurements (LH, FSH, testosterone) were performed in 29 patients after orchiectomy for seminoma before and after irradiation. Before radiotherapy 14 of 20 orchiectomised patients were azoospermic or had impaired spermatogenesis. A minimum sperm count was found 1 year after radiotherapy with gradual improvement up to 2 years. The recovery of sperm cell production was impaired most in patients with pre-treatment sperm counts < 3 million/ ml. Serum testosterone remained at low normal levels throughout the observation period. The mean serum FSH was increased 1 year after radiotherapy but returned to normal in 50% of patients within 3 years after treatment. This post-treatment increase in FSH was significantly correlated with increased pre-treatment FSH but not with the gonadal dose, which was 1 to 3% of the target dose. Severe disturbances in spermatogenesis, observed 2 to 3 years after radiotherapy for early seminoma, are likely to be the expression of a highly impaired pre-treatment sperm cell production and only to a lesser degree dependent on the irradiation of the remaining testicle. (author)

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

    International Nuclear Information System (INIS)

    Noel, G.; Mazeron, J.J.

    2000-01-01

    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)

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

    Science.gov (United States)

    Handkiewicz-Junak, Daria; Swierniak, Michal; Rusinek, Dagmara; Oczko-Wojciechowska, Małgorzata; Dom, Genevieve; Maenhaut, Carine; Unger, Kristian; Detours, Vincent; Bogdanova, Tetiana; Thomas, Geraldine; Likhtarov, Ilya; Jaksik, Roman; Kowalska, Malgorzata; Chmielik, Ewa; Jarzab, Michal; Swierniak, Andrzej; Jarzab, Barbara

    2016-07-01

    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 Chernobyl PTC are associated with previous low-dose radiation exposure.

  14. Post-traumatic Growth in Breast Cancer Patients: A Qualitative Phenomenological Study

    Directory of Open Access Journals (Sweden)

    Rahele Fallah

    2012-04-01

    Full Text Available Background: Studies about cancer-related trauma have shown that psychological reactions to the disease are not exclusively negative but most patients also report positive experiences. These positive perceptions are also called post-traumatic growth and benefit patients psychologically, spiritually, and physically. Therefore,we have conducted a study about how women with breast cancer perceive posttraumatic growth and the recognition of its dimensions in Iran.Methods: This qualitative study was conducted by using Interpretative Phenomenological Analysis. A total of 23 women with breast cancer who met the inclusion criteria were selected after which patients completed a researcher-generated open-ended questionnaire. Data were analyzed according to the guidelines for the Interpretative Phenomenological Analysis and Smith method.Results: Participants’ perceptions in this study about post-traumatic growth included three themes: spiritual growth, appreciation of life, and increased personal strengths.Conclusion: Themes found in this study conformed to dimensions according to the Tedeschi and Calhoun theory of post-traumatic growth. However, relations with others were not found in the present study. We propose that interventions should be designed and implemented in order to facilitate and enhance post-traumatic growth.

  15. Male breast cancer: 20-year survival data for post-mastectomy radiotherapy.

    Science.gov (United States)

    Eggemann, Holm; Ignatov, Atanas; Stabenow, Roland; von Minckwitz, Gunter; Röhl, Friedrich Wilhelm; Hass, Peter; Costa, Serban-Dan

    2013-08-01

    The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer. We investigated 20-year OS rates of 664 patients diagnosed with primary stage I-III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy. Median follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41-0.88; p = 0.008). Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.

  16. Post-traumatic stress disorder and post-traumatic growth in breast cancer patients--a systematic review.

    Science.gov (United States)

    Parikh, Darshit; De Ieso, Paolo; Garvey, Gail; Thachil, Thanuja; Ramamoorthi, Ramya; Penniment, Michael; Jayaraj, Rama

    2015-01-01

    Breast cancer (BC) is potentially a traumatic stressor which may be associated with negative outcomes, such as post-traumatic stress disorder (PTSD) or positive changes, such as post-traumatic growth (PTG). This study aims to identify the core issues of BC related PTSD, PTG and psychological distress by interrogating the literature in BC survivors. We have also highlighted issues related to the assessment, diagnosis and clinical management of PTSD and PTG. The authors systematically reviewed studies published from 1985 to 2014 pertaining to PTSD, psychological distress and PTG in BC survivors with particular attention paid to incidence rates and causative factors. Multiple studies intimated that women with BC have evidence of PTSD at the initial stages of diagnosis, whereas PTG develops once patients undergo treatment. Early diagnosis and treatment of PTSD/PTG is paramount from literature review but the previously mentioned relationship between PTSD and PTG in BC patients could not be verified. It is evident from the literature that a small percentage of BC patients experience PTSD, while the majority experience PTG after BC diagnosis and treatment. Future research should include prospective studies focusing on high-risk patients, causative factors and the development of psychological interventions.

  17. Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

    Science.gov (United States)

    Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

    2017-12-15

    The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Prescription patterns of Chinese herbal products for post-surgery colon cancer patients in Taiwan.

    Science.gov (United States)

    Chao, Te-Hsin; Fu, Pin-Kuei; Chang, Chiung-Hung; Chang, Shih-Ni; Chiahung Mao, Frank; Lin, Ching-Heng

    2014-08-08

    Traditional Chinese medicine (TCM) is commonly provided to cancer patients, however, the patterns of prescriptions for this type of medicine in Taiwan are unclear. This study aimed to evaluate the use of traditional Chinese medicine products in colon cancer patients post-surgery in Taiwan and to research patterns of TCM. This was a cross-sectional study of newly diagnosed colon cancer patients who received surgery between 2004 and 2008 identified from the National Health Insurance Research Database of Taiwan. The prescription patterns and reasons for the use of TCM for colon cancer were analyzed. The results showed that "symptoms, signs and ill-defined conditions" (23.3%) and diseases of the digestive system (16.9%) were the most common reasons for using Chinese herbal medicine. Xiang-sha-liu-jun-zi-tang (7.1%), Bu-zhong-yi-qi-tang (4.3%), Jia-wei-xiao-yao-san (4.1%), Shen-Ling-Bai-Zhu-San (3.7%), Ban-Xia-Xie-Xin-Tang (3.4%), Gui-pi-tang (2.4%), Ping-Wei-San (2.4%), Gan-Lu-Yin (2.0%), Bao-He-Wan (1.9%), and Zhen-Ren-Huo-Ming-Yin (1.8%) were the most commonly prescribed single Chinese herbal formulae (CHF) for colon cancer patients post-surgery. Hedyotis diffusa Willd (Bai Hua She She Cao) (5.1%) and Scutellaria barbata (Ban Zhi Lian )(4.8%) were the most commonly prescribed single Chinese herbs. This study identified patterns of TCM use in colon cancer patients post-surgery in Taiwan. The herbal ingredients were most commonly used for stimulate ghrelin secretion to increase food intake and had potential anti-tumor effect. However, further research is required to evaluate any beneficial effects which could identify leads for the development of new treatment strategies using TCM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Serum Leptin and Adiponectin Levels in Breast Cancer Before and After Post Mastectomy Radiotherapy

    International Nuclear Information System (INIS)

    Nosseir, N.M.; Abdel -Messeih, Ph.L.; Mohamed, S.K.

    2010-01-01

    Obesity is a risk factor for postmenopausal breast cancer and is associated with poor prognosis. Leptin and adiponectin are cytokines synthesized in adipose tissue and have been implicated as a link between obesity and breast cancer. Therefore, in this study we analyzed and compared: serum leptin, adiponectin, lipid profile including cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) and body mass index (BMI) in breast cancer patients before and after Post Mastectomy Radio- therapy (PMRT).Serum leptin and adiponectin significantly increased and decreased respectively in patients after PMRT compared to the controls. BMI statistically decreased after radiotherapy while LDL-c increased in breast cancer patients; in both patients groups. HDL-c was statistically decreased but triglycerides showed significant increase in breast cancer patients. These results denoted that dyslipidemia may be associated with breast cancer risk and the evaluation of leptin and adiponectin can be used for follow up of patients under radiotherapy treatment for breast cancer

  20. Serum Leptin and Adiponectin Levels in Breast Cancer Before and After Post Mastectomy Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nosseir, N M; Abdel -Messeih, Ph L; Mohamed, S.K., E-mail: neveennosseir@Live.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P.O.Box:29 Nasr City-Cairo (Egypt)

    2010-07-01

    Obesity is a risk factor for postmenopausal breast cancer and is associated with poor prognosis. Leptin and adiponectin are cytokines synthesized in adipose tissue and have been implicated as a link between obesity and breast cancer. Therefore, in this study we analyzed and compared: serum leptin, adiponectin, lipid profile including cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) and body mass index (BMI) in breast cancer patients before and after Post Mastectomy Radio- therapy (PMRT).Serum leptin and adiponectin significantly increased and decreased respectively in patients after PMRT compared to the controls. BMI statistically decreased after radiotherapy while LDL-c increased in breast cancer patients; in both patients groups. HDL-c was statistically decreased but triglycerides showed significant increase in breast cancer patients. These results denoted that dyslipidemia may be associated with breast cancer risk and the evaluation of leptin and adiponectin can be used for follow up of patients under radiotherapy treatment for breast cancer

  1. Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

    International Nuclear Information System (INIS)

    Gregoire, Vincent; Hamoir, Marc; Chen Changhu; Kane, Madeleine; Kawecki, Andrzej; Julka, Pramod K.; Wang, Hung-Ming; Prasad, Srihari; D'Cruz, Anil K.; Radosevic-Jelic, Ljiljana; Kumar, Rejnish R.; Korzeniowski, Stanislaw; Fijuth, Jacek; Machiels, Jean-Pascal; Sellers, Mark V.; Tchakov, Ilian; Raben, David

    2011-01-01

    Background and purpose: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. Materials and methods: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability. Results: Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. Conclusion: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

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

    DEFF Research Database (Denmark)

    Krogsgaard, Marianne; Dreyer, Pia; Egerod, Ingrid

    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...... a phenomenological hermeneutical approach. RESULTS: During the first two weeks after discharge the patients experienced unfamiliar symptoms that affected their everyday lives. Despite distressing symptoms, they applied a "wait-and-see" strategy, and only reacted when symptoms became intolerable. The patients failed...... 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 encouraged...

  3. 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.

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

    International Nuclear Information System (INIS)

    Lee, Joo Young; Han, Hye-Suk; Lim, Sung-Nam; Shim, Young Kwang; Choi, Yong Hyeok; Lee, Ok-Jun; Lee, Ki Hyeong; Kim, Seung Taik

    2012-01-01

    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. 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. 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

  5. Aging, obesity, and post-therapy cognitive recovery in breast cancer survivors.

    Science.gov (United States)

    Huang, Zhezhou; Zheng, Ying; Bao, Pingping; Cai, Hui; Hong, Zhen; Ding, Ding; Jackson, James; Shu, Xiao-Ou; Dai, Qi

    2017-02-14

    Therapy-induced cognitive impairment is prevalent and long-lasting in cancer survivors, but factors affecting post-therapy cognitive recovery are unclear. We conducted this study to evaluate the associations of age, body mass index (BMI), waist-to-hip ratio (WHR), and physical activity (PA) with post-therapy cognitive changes in a population-based breast cancer (BC) survivor cohort. We collected information on PA, weight, height, waist and hip circumferences of 1286 BC survivors aged 20-75. We assessed their cognitive functions, including immediate memory, delayed memory, verbal fluency, and attention, at 18 and 36 months after cancer diagnosis. Linear regression models were used to examine the associations of age, BMI, WHR and PA with mean changes in cognitive scores from 18- to 36-month follow-up interview. We found that the post-therapy cognitive changes differed by age and obesity status. Verbal fluency and attention improved in younger patients aged therapy cognitive change. Due to the novelty of our findings and the limitations of our study, further research, including intervention trials, is warranted to confirm the causal relationship between obesity and cognitive impairments.

  6. 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

    2007-01-01

    of the segments of the gastrointestinal tract were determined, and histologic sections were analyzed by morphometric methods. RESULTS: A significant atrophy of the small-intestinal wall was observed after treatment with gefitinib because both intestinal weight and morphometrically estimated villus height...

  7. 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

  8. Acquisition of Social Support and Linguistic Characteristics of Social Media Posts About Young Adult Cancer.

    Science.gov (United States)

    Warner, Echo L; Ellington, Lee; Kirchhoff, Anne C; Cloyes, Kristin G

    2018-04-01

    Social media (SM) is a burgeoning source of social support for young adults (YAs). We explored the language used to communicate about YA cancer on Instagram and for indicators of social support (i.e., number of likes and comments). Instagram posts using #youngadultcancer were randomly selected (N = 50). Text and hashtags were collected, and posts were coded for gender (female and male), treatment status (active treatment and survivorship), type of user (individual and organization), and caregiver status (yes and no). Indicators of social support, valence (e.g., positive vs. negative terms), and lexical content (e.g., emotional terms and pronouns) were measured using Yoshikoder and Linguistic Inquiry Word Count and compared by gender, treatment status, type of user, and caregiver status. Survivors' posts had more likes compared to those in active treatment (mean: 54.5 vs. 32.3, p = 0.03). Individuals' posts had more comments than those of organizations (mean: 5.3 vs. 1.2, p = 0.01). More positive (30%) than negative (13%) terms were used by survivors (p Instagram users communicate about YA cancer and whether the language they use garners social support. Studying online language use may help YA patients, caregivers, and organizations use SM to gain social support.

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

    International Nuclear Information System (INIS)

    Begum, M.; Khurshid, R.; Nagra, S.A.

    2008-01-01

    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)

  10. [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.

  11. Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia

    Science.gov (United States)

    Mota, Roberto; Rodríguez, Jessica E; Bonetto, Andrea; O’Connell, Thomas M; Asher, Scott A; Parry, Traci L; Lockyer, Pamela; McCudden, Christopher R; Couch, Marion E; Willis, Monte S

    2017-01-01

    Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. Up to 80% of cancer patients experience cachexia, with 20-30% of cancer-related deaths directly linked to cachexia. Despite efforts to identify early cachexia and cancer relapse, clinically useful markers are lacking. Recently, we identified the role of muscle-specific ubiquitin ligases Atrogin-1 (MAFbx, FBXO32) and Muscle Ring Finger-1 in the pathogenesis of cardiac atrophy and hypertrophy. We hypothesized that during cachexia, the Atrogin-1 and MuRF1 ubiquitin ligases are released from muscle and migrate to the circulation where they could be detected and serve as a cachexia biomarker. To test this, we induced cachexia in mice using the C26 adenocarcinoma cells or vehicle (control). Body weight, tumor volume, and food consumption were measured from inoculation until ~day 14 to document cachexia. Western blot analysis of serum identified the presence of Atrogin-1 and MuRF1 with unique post-translational modifications consistent with mono- and poly- ubiquitination of Atrogin-1 and MuRF1 found only in cachectic serum. These findings suggest that both increased Atrogin-1 and the presence of unique post-translational modifications may serve as a surrogate marker specific for cachexia. PMID:28979816

  12. The impact of bladder preparation protocols on post treatment toxicity in radiotherapy for localised prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Yat Man Tsang

    2017-09-01

    Conclusion: The empty bladder preparation approach has non-inferior acute and intermediate post RT GI and GU toxicities in patients treated for localised prostate cancer with advanced radiotherapy techniques compared to the full bladder preparation.

  13. Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

    National Research Council Canada - National Science Library

    Hrushesky, William

    2002-01-01

    It is hypothesized that the short term objectives of doing this proposal are to better understand which sex steroids and which cellular immune functions control post resection metastatic cancer spread...

  14. Pre and post PET-CT impact on oesophageal cancer management: a retrospective analysis.

    Science.gov (United States)

    Azmi, NA; Razak, HRA; Vinjamuri, S.

    2017-05-01

    Assessment of the retrospective cancer incidence, prevalence and crude survival rates of oesophageal cancer to allow comparison between pre and post PET-CT introduction are part of 4 phase cost effectiveness research. It will provide baseline data for to assess PET or PET-CT cost effective potential for staging. A total of 849 patient’s data received from NWCIS databases with various stages of oesophageal cancer between 2001 and 2008. The fundamental activities are retrospective analysis of patient data. In most cases where appropriate, results are presented with 95 percent confidence intervals (CI). Variances between patient groups and variables are assessed using chi-square test. In cases where it deems vital, multiple logistic regression are used to modify for potential confounder such as age and sex. All p-values are two-sided and any value lower than 0.05 were considered to suggest a statistically significant result. Retrospective analysis were categorised into two categories, patients from 2001-2003 considered as pre PET and post PET for 2004-2008. This categorisation allows better comparison of patients’ survival trend to be made between both groups. Rates are presented in percentages and being grouped by tumour characteristics and other variables associated with demographic profile, diagnosis, staging and treatment. Results allowed comparison of oesophageal cancer trends between the pre and post PET-CT introduction such as changes in incidence rate or changes in survival. These data were used to normalise the decision tree model so that cost-effectiveness analysis can be performed across the whole population.

  15. Pre and post PET-CT impact on oesophageal cancer management: a retrospective analysis

    International Nuclear Information System (INIS)

    Azmi, NA; Razak, HRA; Vinjamuri, S

    2017-01-01

    Assessment of the retrospective cancer incidence, prevalence and crude survival rates of oesophageal cancer to allow comparison between pre and post PET-CT introduction are part of 4 phase cost effectiveness research. It will provide baseline data for to assess PET or PET-CT cost effective potential for staging. A total of 849 patient’s data received from NWCIS databases with various stages of oesophageal cancer between 2001 and 2008. The fundamental activities are retrospective analysis of patient data. In most cases where appropriate, results are presented with 95 percent confidence intervals (CI). Variances between patient groups and variables are assessed using chi-square test. In cases where it deems vital, multiple logistic regression are used to modify for potential confounder such as age and sex. All p-values are two-sided and any value lower than 0.05 were considered to suggest a statistically significant result. Retrospective analysis were categorised into two categories, patients from 2001-2003 considered as pre PET and post PET for 2004-2008. This categorisation allows better comparison of patients’ survival trend to be made between both groups. Rates are presented in percentages and being grouped by tumour characteristics and other variables associated with demographic profile, diagnosis, staging and treatment. Results allowed comparison of oesophageal cancer trends between the pre and post PET-CT introduction such as changes in incidence rate or changes in survival. These data were used to normalise the decision tree model so that cost-effectiveness analysis can be performed across the whole population. (paper)

  16. Influence of accompanying immunocorrecting therapy on the quality of life of breast cancer patients at post-operative radiation therapy

    International Nuclear Information System (INIS)

    Prokhach, N.E.

    2013-01-01

    To investigate the influence of accompanying immunotherapy on the parameters of the quality of life of the patients with breast cancer with various profiles of cytokines at post-operative radiation therapy. The study was performed on 30 breast cancer patients at stages of combination therapy

  17. Post-treatment surveillance in a large cohort of patients with colon cancer.

    Science.gov (United States)

    Hu, Chung-Yuan; Delclos, George L; Chan, Wenyaw; Du, Xianglin L

    2011-05-01

    To determine how patients complied with different components of guideline-recommended post-treatment surveillance in a large nationwide population-based cohort of patients with colon cancer. Retrospective cohort study. We used the linked Surveillance, Epidemiology, and End Results-Medicare database to identify patients 66 years or older diagnosed as having stage I to stage III colon adenocarcinoma between January 2000 and June 2002 with a follow-up duration of at least 3.5 years. After tumor resection, patients who completed at least 2 office visits per year for 3 years, at least 2 carcinoembryonic antigen tests per year (in the first and second years of follow-up), and at least 1 colonoscopy within 3 years were defined as meeting the recommended post-treatment care. We identified 7348 patients, with a median follow-up duration of 59 months. Adherence to post-treatment surveillance was 83.9% for office visits, 29.4% for carcinoembryonic antigen tests, and 74.3% for colonoscopy. Younger age at diagnosis, white race/ethnicity, married status, advanced tumor stage, fewer comorbidities, and chemotherapy use were significantly associated with guideline adherence. Adherence to colon cancer posttreatment surveillance was low, although proportions of patients complying with office visits and colonoscopy were reasonably high. Underlying reasons for noncompliance, which varied by type of service, may need further investigation.

  18. 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.)

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

    International Nuclear Information System (INIS)

    Helenius, Malin; Dahlman, Par; Lonnemark, Maria; Magnusson, Anders; Brekkan, Einar; Wernroth, Lisa

    2016-01-01

    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.)

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

    International Nuclear Information System (INIS)

    Klausner, Richard D.

    1996-01-01

    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

  1. Abdominal drainage versus no drainage post-gastrectomy for gastric cancer.

    Science.gov (United States)

    Wang, Zhen; Chen, Junqiang; Su, Ka; Dong, Zhiyong

    2015-05-11

    Gastrectomy remains the primary therapeutic method for resectable gastric cancer. Thought of as an important measure to reduce post-operative complications and mortality, abdominal drainage has been used widely after gastrectomy for gastric cancer in previous decades. The benefits of abdominal drainage have been questioned by researchers in recent years. The objectives of this review were to assess the benefits and harms of routine abdominal drainage post-gastrectomy for gastric cancer. We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 11); MEDLINE (via PubMed) (1950 to November 2014); EMBASE (1980 to November 2014); and the Chinese National Knowledge Infrastructure (CNKI) Database (1979 to November 2014). We included randomised controlled trials (RCTs) comparing an abdominal drain versus no drain in patients who had undergone gastrectomy (not considering the scale of gastrectomy and the extent of lymphadenectomy); irrespective of language, publication status, and the type of drain. We excluded RCTs comparing one drain with another. We adhered to the standard methodological procedures of The Cochrane Collaboration. From each included trial, we extracted the data on the methodological quality and characteristics of the participants, mortality (30-day mortality), re-operations, post-operative complications (pneumonia, wound infection, intra-abdominal abscess, anastomotic leak, drain-related complications), operation time, length of post-operative hospital stay, and initiation of a soft diet. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous data, we calculated mean difference (MD) and 95% CI. We tested heterogeneity using the Chi(2) test. We used a fixed-effect model for data analysis with RevMan software, but we used a random-effects model if the P value of

  2. Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD.

    Science.gov (United States)

    Wu, Ming-Fang; Jian, Zhi-Hong; Huang, Jing-Yang; Jan, Cheng-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Liaw, Yung-Po

    2016-10-10

    Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.

  3. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-01-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer

  4. Extensive and systematic rewiring of histone post-translational modifications in cancer model systems.

    Science.gov (United States)

    Noberini, Roberta; Osti, Daniela; Miccolo, Claudia; Richichi, Cristina; Lupia, Michela; Corleone, Giacomo; Hong, Sung-Pil; Colombo, Piergiuseppe; Pollo, Bianca; Fornasari, Lorenzo; Pruneri, Giancarlo; Magnani, Luca; Cavallaro, Ugo; Chiocca, Susanna; Minucci, Saverio; Pelicci, Giuliana; Bonaldi, Tiziana

    2018-05-04

    Histone post-translational modifications (PTMs) generate a complex combinatorial code that regulates gene expression and nuclear functions, and whose deregulation has been documented in different types of cancers. Therefore, the availability of relevant culture models that can be manipulated and that retain the epigenetic features of the tissue of origin is absolutely crucial for studying the epigenetic mechanisms underlying cancer and testing epigenetic drugs. In this study, we took advantage of quantitative mass spectrometry to comprehensively profile histone PTMs in patient tumor tissues, primary cultures and cell lines from three representative tumor models, breast cancer, glioblastoma and ovarian cancer, revealing an extensive and systematic rewiring of histone marks in cell culture conditions, which includes a decrease of H3K27me2/me3, H3K79me1/me2 and H3K9ac/K14ac, and an increase of H3K36me1/me2. While some changes occur in short-term primary cultures, most of them are instead time-dependent and appear only in long-term cultures. Remarkably, such changes mostly revert in cell line- and primary cell-derived in vivo xenograft models. Taken together, these results support the use of xenografts as the most representative models of in vivo epigenetic processes, suggesting caution when using cultured cells, in particular cell lines and long-term primary cultures, for epigenetic investigations.

  5. Impact of symptom burden in post-surgical non-small cell lung cancer survivors.

    Science.gov (United States)

    Lowery, Amy E; Krebs, Paul; Coups, Elliot J; Feinstein, Marc B; Burkhalter, Jack E; Park, Bernard J; Ostroff, Jamie S

    2014-01-01

    Pain, fatigue, dyspnea, and distress are commonly reported cancer-related symptoms, but few studies have examined the effects of multiple concurrent symptoms in longer-term cancer survivors. We examined the impact of varying degrees of symptom burden on health-related quality of life (HRQOL) and performance status in surgically treated non-small cell lung cancer (NSCLC) survivors. A sample of 183 NSCLC survivors 1-6 years post-surgical treatment completed questionnaires assessing five specific symptoms (pain, fatigue, dyspnea, depression, and anxiety), HRQOL, and performance status. The number of concurrent clinically significant symptoms was calculated as an indicator of symptom burden. Most survivors (79.8 %) had some degree of symptom burden, with 30.6 % reporting one clinically significant symptom, 27.9 % reporting two symptoms, and 21.3 % reporting three or more symptoms. Physical HRQOL significantly decreased as the degree of symptom burden increased, but mental HRQOL was only significantly decreased in those with three or more symptoms. Receiver-operating characteristic (ROC) curves showed that having multiple concurrent symptoms (two or more) was most likely associated with limitations in functioning (area under a ROC curve = 0.75, sensitivity = 0.81, specificity = 0.54). Two or more clinically significant symptoms are identified as the "tipping point" for showing adverse effects on HRQOL and functioning. This highlights the need for incorporating multiple-symptom assessment into routine clinical practice. Comprehensive symptom management remains an important target of intervention for improved post-treatment HRQOL and functioning among lung cancer survivors.

  6. Randomized Evaluation of Cognitive-Behavioral Therapy and Graded Exercise Therapy for Post-Cancer Fatigue.

    Science.gov (United States)

    Sandler, Carolina X; Goldstein, David; Horsfield, Sarah; Bennett, Barbara K; Friedlander, Michael; Bastick, Patricia A; Lewis, Craig R; Segelov, Eva; Boyle, Frances M; Chin, Melvin T M; Webber, Kate; Barry, Benjamin K; Lloyd, Andrew R

    2017-07-01

    Cancer-related fatigue is prevalent and disabling. When persistent and unexplained, it is termed post-cancer fatigue (PCF). Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) may improve symptoms and functional outcomes. To evaluate the outcomes of a randomized controlled trial, which assigned patients with post-cancer fatigue to education, or 12 weeks of integrated cognitive-behavioral therapy (CBT) and graded exercise therapy (GET). Three months after treatment for breast or colon cancer, eligible patients had clinically significant fatigue, no comorbid medical or psychiatric conditions that explained the fatigue, and no evidence of recurrence. The CBT/GET arm included individually tailored consultations at approximately two weekly intervals. The education arm included a single visit with clinicians describing the principles of CBT/GET and a booklet. The primary outcome was clinically significant improvement in self-reported fatigue (Somatic and Psychological HEalth REport 0-12), designated a priori as greater than one SD of improvement in fatigue score. The secondary outcome was associated improvement in function (role limitation due to physical health problems-36-Item Short Form Health Survey 0-100) comparing baseline, end treatment (12 weeks), and follow-up (24 weeks). There were 46 patients enrolled, including 43 women (94%), with a mean age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (±3.1) at baseline to 3.9 (±2.8) at 12 weeks, suggesting a natural history of improvement. Clinically significant improvement was observed in 7 of 22 subjects in the intervention group compared with 2 of 24 in the education group (P < 0.05, χ 2 ). These subjects also had improvement in functional status compared with nonresponders (P < 0.01, t-test). Combined CBT/GET improves fatigue and functional outcomes for a subset of patients with post-cancer fatigue. Further studies to improve the response rate and the magnitude of

  7. Blog Posting After Lung Cancer Notification: Content Analysis of Blogs Written by Patients or Their Families.

    Science.gov (United States)

    Sato, Akira; Aramaki, Eiji; Shimamoto, Yumiko; Tanaka, Shiro; Kawakami, Koji

    2015-05-18

    The advent and spread of the Internet has changed the way societies communicate. A portion of information on the Internet may constitute an important source of information concerning the experiences and thoughts of patients and their families. Patients and their families use blogs to obtain updated information, search for alternative treatments, facilitate communication with other patients, and receive emotional support. However, much of this information has yet to be actively utilized by health care professionals. We analyzed health-related information in blogs from Japan, focusing on the feelings and satisfaction levels of lung cancer patients or their family members after being notified of their disease. We collected 100 blogs written in Japanese by patients (or their families) who had been diagnosed with lung cancer by a physician. These 100 blogs posts were searchable between June 1 and June 30, 2013. We focused on blog posts that addressed the lung cancer notification event. We analyzed the data using two different approaches (Analysis A and Analysis B). Analysis A was blog content analysis in which we analyzed the content addressing the disease notification event in each blog. Analysis B was patient's dissatisfaction and anxiety analysis. Detailed blog content regarding patient's dissatisfaction and anxiety at the individual sentence level was coded and analyzed. The 100 blog posts were written by 48 men, 46 women, and 6 persons whose sex was undisclosed. The average age of the blog authors was 52.4 years. With regard to cancer staging, there were 5 patients at Stage I, 3 patients at Stage II, 14 patients at Stage III, 21 patients at Stage IV, and 57 patients without a disclosed cancer stage. The results of Analysis A showed that the proportion of patients who were dissatisfied with the level of health care exceeded that of satisfied patients (22% vs 8%). From the 2499 sentences in the 100 blog posts analyzed, we identified expressions of dissatisfaction and

  8. Surgical treatments for post-irradiation intestinal injury in uterine cervix cancer patients

    International Nuclear Information System (INIS)

    Nozaki, Isao; Yokoyama, Nobuji; Takashima, Shigemitsu

    1997-01-01

    We examined 19 patients with post-irradiation intestinal injury in the uterine cervix cancer for 12 years between 1985 and 1996. We discuss the usefulness and complications of surgery, mainly colostomy. The patients aged from 36 to 80 (average age 61) were treated, and their disease states were 12 cases of rectovaginal fistula, 2 of small intestinal fisfula, 1 of rectum posterior membranous fistula, 3 of proctostenosis, and 14 of proctitis with hemorrhage (including duplication). Surgical methods used were 18 cases of colostomy (2 cases were treated under peritoneum mirror) and 2 of enterocolostomy (including duplication). Eleven out of 19 patients who underwent surgery are alive now. Generally the post-irradiation intestinal injury was intractable, and the method of treatments were limited due to the coexistence of various diseases. The colostomy is safe and less invasive. Therefore patients with uterine cervix cancer having various complications can obtain high quality of life (QOL) such as the improvement of anemia and/or the increase of digestion by the colostomy. (K.H.)

  9. Surgical treatments for post-irradiation intestinal injury in uterine cervix cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Isao; Yokoyama, Nobuji; Takashima, Shigemitsu [National Shikoku Cancer Center Hospital, Matsuyama, Ehime (Japan)

    1997-06-01

    We examined 19 patients with post-irradiation intestinal injury in the uterine cervix cancer for 12 years between 1985 and 1996. We discuss the usefulness and complications of surgery, mainly colostomy. The patients aged from 36 to 80 (average age 61) were treated, and their disease states were 12 cases of rectovaginal fistula, 2 of small intestinal fisfula, 1 of rectum posterior membranous fistula, 3 of proctostenosis, and 14 of proctitis with hemorrhage (including duplication). Surgical methods used were 18 cases of colostomy (2 cases were treated under peritoneum mirror) and 2 of enterocolostomy (including duplication). Eleven out of 19 patients who underwent surgery are alive now. Generally the post-irradiation intestinal injury was intractable, and the method of treatments were limited due to the coexistence of various diseases. The colostomy is safe and less invasive. Therefore patients with uterine cervix cancer having various complications can obtain high quality of life (QOL) such as the improvement of anemia and/or the increase of digestion by the colostomy. (K.H.)

  10. Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

    Science.gov (United States)

    Hansen, Eric; Panwala, Kathryn; Holland, John

    2002-11-01

    Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

  11. Identifying predictive motor factors for falls in post-menopausal breast cancer survivors.

    Directory of Open Access Journals (Sweden)

    Marek Zak

    Full Text Available Breast cancer treatment, including radical surgery, is also pursued as late as the 7th - 8th decade of women's lives. Standard physical rehabilitation procedures offered to those women are predominantly focused on attenuating specific functional deficits of the upper limb and trunk. Seldom do they entail any regimens specifically aimed at recovering overall functionality, and reducing exposure to falls-risk. The study aimed to assess potential interrelationships between the self-reported falls, individual functional capabilities and appreciably reducing exposure to falls-risk in a group of post-menopausal, post-surgical breast cancer survivors.The study recruited 102 women (aged 65-79; mean age 70.2, post-surgical breast cancer survivors. The subjects were stratified by age into three groups: Group 1 (65-69 years; Group 2 (70-74 years, and Group 3 (75-79 years. Individual functional capabilities were assessed with Eight-foot up & go test (8UG, chair stand test (CST, and 2-minute step test (2ST. Tinetti POMA test was applied to assess gait and balance disorders. Self-reported falls in the past year were ascertained through a questionnaire.Assessment of individual aerobic endurance (2ST also demonstrated a clear deficit in the mean scores category in all respective age sub-groups, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values; the oldest subjects demonstrating the largest deficit. The aerobic endurance tests results significantly impacted the ultimate assessment of an individual falls-risk in the oldest group. The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such incidents.An individual exposure to falls-risk was found to be appreciably more dependent upon individual aerobic endurance rather than overall strength of the lower part of the body in the breast cancer survivors over 75.

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

    International Nuclear Information System (INIS)

    Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F.; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena

    2012-01-01

    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. -- 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.

  13. Locally advanced rectal cancer: post-chemoradiotherapy ADC histogram analysis for predicting a complete response.

    Science.gov (United States)

    Cho, Seung Hyun; Kim, Gab Chul; Jang, Yun-Jin; Ryeom, Hunkyu; Kim, Hye Jung; Shin, Kyung-Min; Park, Jun Seok; Choi, Gyu-Seog; Kim, See Hyung

    2015-09-01

    The value of diffusion-weighted imaging (DWI) for reliable differentiation between pathologic complete response (pCR) and residual tumor is still unclear. Recently, a few studies reported that histogram analysis can be helpful to monitor the therapeutic response in various cancer research. To investigate whether post-chemoradiotherapy (CRT) apparent diffusion coefficient (ADC) histogram analysis can be helpful to predict a pCR in locally advanced rectal cancer (LARC). Fifty patients who underwent preoperative CRT followed by surgery were enrolled in this retrospective study, non-pCR (n = 41) and pCR (n = 9), respectively. ADC histogram analysis encompassing the whole tumor was performed on two post-CRT ADC600 and ADC1000 (b factors 0, 600 vs. 0, 1000 s/mm(2)) maps. Mean, minimum, maximum, SD, mode, 10th, 25th, 50th, 75th, 90th percentile ADCs, skewness, and kurtosis were derived. Diagnostic performance for predicting pCR was evaluated and compared. On both maps, 10th and 25th ADCs showed better diagnostic performance than that using mean ADC. Tenth percentile ADCs revealed the best diagnostic performance on both ADC600 (AZ 0.841, sensitivity 100%, specificity 70.7%) and ADC1000 (AZ 0.821, sensitivity 77.8%, specificity 87.8%) maps. In comparison between 10th percentile and mean ADC, the specificity was significantly improved on both ADC600 (70.7% vs. 53.7%; P = 0.031) and ADC1000 (87.8% vs. 73.2%; P = 0.039) maps. Post-CRT ADC histogram analysis is helpful for predicting pCR in LARC, especially, in improving the specificity, compared with mean ADC. © The Foundation Acta Radiologica 2014.

  14. 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.

  15. Impaired swallowing mechanics of post radiation therapy head and neck cancer patients: A retrospective videofluoroscopic study.

    Science.gov (United States)

    Pearson, William G; Davidoff, Alisa A; Smith, Zachary M; Adams, Dorothy E; Langmore, Susan E

    2016-02-28

    To determine swallowing outcomes and hyolaryngeal mechanics associated with post radiation therapy head and neck cancer (rtHNC) patients using videofluoroscopic swallow studies. In this retrospective cohort study, videofluoroscopic images of rtHNC patients (n = 21) were compared with age and gender matched controls (n = 21). Penetration-aspiration of the bolus and bolus residue were measured as swallowing outcome variables. Timing and displacement measurements of the anterior and posterior muscular slings elevating the hyolaryngeal complex were acquired. Coordinate data of anatomical landmarks mapping the action of the anterior muscles (suprahyoid muscles) and posterior muscles (long pharyngeal muscles) were used to calculate the distance measurements, and slice numbers were used to calculate time intervals. Canonical variate analysis with post-hoc discriminant function analysis was performed on coordinate data to determine multivariate mechanics of swallowing associated with treatment. Pharyngeal constriction ratio (PCR) was also measured to determine if weak pharyngeal constriction is associated with post radiation therapy. The rtHNC group was characterized by poor swallowing outcomes compared to the control group in regards to: Penetration-aspiration scale (P time of displacement was abbreviated (P = 0.002) and distance of excursion was reduced (P = 0.02) in the rtHNC group. A canonical variate analysis shows a significant reduction in pharyngeal mechanics in the rtHNC group (P clearance. Using videofluoroscopy, this study shows rtHNC patients have worse swallowing outcomes associated with reduced hyolaryngeal mechanics and pharyngeal constriction compared with controls.

  16. Quality Assurance of Cancer Study Common Data Elements Using A Post-Coordination Approach.

    Science.gov (United States)

    Jiang, Guoqian; Solbrig, Harold R; Prud'hommeaux, Eric; Tao, Cui; Weng, Chunhua; Chute, Christopher G

    2015-01-01

    Domain-specific common data elements (CDEs) are emerging as an effective approach to standards-based clinical research data storage and retrieval. A limiting factor, however, is the lack of robust automated quality assurance (QA) tools for the CDEs in clinical study domains. The objectives of the present study are to prototype and evaluate a QA tool for the study of cancer CDEs using a post-coordination approach. The study starts by integrating the NCI caDSR CDEs and The Cancer Genome Atlas (TCGA) data dictionaries in a single Resource Description Framework (RDF) data store. We designed a compositional expression pattern based on the Data Element Concept model structure informed by ISO/IEC 11179, and developed a transformation tool that converts the pattern-based compositional expressions into the Web Ontology Language (OWL) syntax. Invoking reasoning and explanation services, we tested the system utilizing the CDEs extracted from two TCGA clinical cancer study domains. The system could automatically identify duplicate CDEs, and detect CDE modeling errors. In conclusion, compositional expressions not only enable reuse of existing ontology codes to define new domain concepts, but also provide an automated mechanism for QA of terminological annotations for CDEs.

  17. Post-Traumatic Growth and Resilience in Adolescent and Young Adult Cancer Patients: An Overview.

    Science.gov (United States)

    Greup, Suzanne R; Kaal, Suzanne E J; Jansen, Rosemarie; Manten-Horst, Eveliene; Thong, Melissa S Y; van der Graaf, Winette T A; Prins, Judith B; Husson, Olga

    2018-02-01

    The aim of this study was to provide an overview of the literature on post-traumatic growth (PTG) and resilience among adolescent and young adult (AYA) cancer patients. A literature search in Embase, PsychInfo, PubMed, Web of Science, Cochrane Library, and Cinahl was carried out. Thirteen articles met the pre-defined inclusion criteria. Qualitative interview studies showed that AYA cancer patients report PTG and resilience: PTG is described by AYA cancer patients in terms of benefit finding, including changing view of life and feeling stronger and more confident, whereas resilience is described as a balance of several factors, including stress and coping, goals, optimism, finding meaning, connection, and belonging. Quantitative studies showed that sociodemographic and clinical characteristics were not associated with PTG. Enduring stress was negatively, and social support positively, associated with PTG. Symptom distress and defensive coping were negatively and adaptive cognitive coping was positively associated with resilience. Both PTG and resilience were positively associated with satisfaction with life and health-related quality of life (HRQoL). Resilience was found to be a mediator in the relationship between symptom distress and HRQoL. Two interventions aiming to promote resilience, a stress management and a therapeutic music video-intervention, were not successful in significantly increasing overall resilience. Most AYA cancer patients report at least some PTG or resilience. Correlates of PTG and resilience, including symptom distress, stress, coping, social support, and physical activity, provide further insight to improve the effectiveness of interventions aimed at promoting these positive outcomes and potentially buffer negative outcomes.

  18. Post-bronchoscopy pneumonia in patients suffering from lung cancer: Development and validation of a risk prediction score.

    Science.gov (United States)

    Takiguchi, Hiroto; Hayama, Naoki; Oguma, Tsuyoshi; Harada, Kazuki; Sato, Masako; Horio, Yukihiro; Tanaka, Jun; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Nakagawa, Tomoki; Masuda, Ryota; Aoki, Takuya; Urano, Tetsuya; Iwazaki, Masayuki; Asano, Koichiro

    2017-05-01

    The incidence, risk factors, and consequences of pneumonia after flexible bronchoscopy in patients with lung cancer have not been studied in detail. We retrospectively analyzed the data from 237 patients with lung cancer who underwent diagnostic bronchoscopy between April 2012 and July 2013 (derivation sample) and 241 patients diagnosed between August 2013 and July 2014 (validation sample) in a tertiary referral hospital in Japan. A score predictive of post-bronchoscopy pneumonia was developed in the derivation sample and tested in the validation sample. Pneumonia developed after bronchoscopy in 6.3% and 4.1% of patients in the derivation and validation samples, respectively. Patients who developed post-bronchoscopy pneumonia needed to change or cancel their planned cancer therapy more frequently than those without pneumonia (56% vs. 6%, ppneumonia, which we added to develop our predictive score. The incidence of pneumonia associated with scores=0, 1, and ≥2 was 0, 3.7, and 13.4% respectively in the derivation sample (p=0.003), and 0, 2.9, and 9.7% respectively in the validation sample (p=0.016). The incidence of post-bronchoscopy pneumonia in patients with lung cancer was not rare and associated with adverse effects on the clinical course. A simple 3-point predictive score identified patients with lung cancer at high risk of post-bronchoscopy pneumonia prior to the procedure. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  19. Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.

    Science.gov (United States)

    Peng, Feng; Hu, Dan; Lin, Xiandong; Liang, Binying; Chen, Ying; Zhang, Hejun; Xia, Yan; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2018-05-24

    Hypertension and diabetes mellitus are common comorbidities of colorectal cancer. We designed a prospective cohort study aiming to investigate the impact of long-term antihypertensive and antidiabetic medications on colorectal cancer-specific survival and recurrence among 713 post-surgical patients. All participants received radical resection for colorectal cancer during 2000-08, and they were followed up until July 2017. Colorectal cancer patients without hypertension had better survival than those with hypertension (median survival time [MST]: 190.3 months versus 99.0 months, p colorectal cancer survival was statistically significant, that is, patients receiving antidiabetic medications had longer survival time than untreated diabetic patients (MST: 135.8 months versus 80.2 months, p : 0.007), whereas the prognosis was greatly improved in colorectal cancer patients without diabetes mellitus ( p colorectal cancer relative to those without medications, respectively. Our data indicate that long-term antidiabetic medications can significantly prolong the survival and improve the prognosis of post-surgical colorectal cancer.

  20. Lipoma of the midbrain: post-mortem finding in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Verônica Maia Gouvea

    1989-09-01

    Full Text Available Intracranial lipomas are rare, usually do not have clinical expression and are located mare frequently in the corpus callosum. Other locations include the spinal cord, midbrain tectum, superior vermis, tuber cinereum, infundibulum and more rarely cerebellopontine angle, hypothalamus, superior medullary velum and insula. We report the case of a lipoma of the left inferior colliculus which was a post-mortem finding in a woman who died of breast cancer. Although there are reports of intracranial lipomas in patients with malignant tumors there is no explanation for the co-existence of the two tumors. The present tumor also includes a segment of a nerve which is not uncommon, but a less common finding was the presence of nests of Schwann cells within it, shown by immunohistochemistry.

  1. Bioengineering/Biophysicist Post-doctoral Fellow | Center for Cancer Research

    Science.gov (United States)

    A post-doctoral fellow position is available in the Tissue Morphodynamics Unit headed by Dr. Kandice Tanner at the National Cancer Institute. The Tanner lab combines biophysical and cell biological approaches to understand the interplay between tissue architecture and metastasis. We use a combination of imaging modalities, cell biology and animal models. It is expected that as a member of this lab, one will have an opportunity to be exposed to all these areas. We value a vibrant and collaborative environment where lab members share ideas, reagents and expertise and want to work on fundamental problems in the establishment of metastatic lesions. Our lab is located in the NIH main campus in Bethesda. The research facilities at NIH are outstanding and the lab has state-of-the-art equipment such as multi-photon and confocal microscopes, FACS facilities and animal vivarium.

  2. Post-Operative Infection Is an Independent Risk Factor for Worse Long-Term Survival after Colorectal Cancer Surgery.

    Science.gov (United States)

    Kerin Povšič, Milena; Ihan, Alojz; Beovič, Bojana

    2016-12-01

    Colorectal cancer surgery is associated with a high incidence of post-operative infections, the outcome of which may be improved if diagnosed and treated early enough. We compared white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT) as predictors of post-operative infections and analyzed their impact on long-term survival. This retrospective study included 186 patients undergoing colorectal surgery. Post-operative values of WBC, CRP, and PCT were analyzed by the receiver operating characteristic (ROC) analysis. We followed infections 30 d after the surgery. A five-year survival was analyzed by Kaplan-Meier method and prognostic factors by Cox regression model. Fifty-five patients (29.5%) developed post-operative infection, the most frequent of which was surgical site infection (SSI). C-reactive protein on post-operative day three and PCT on post-operative day two demonstrated the highest diagnostic accuracy for infection (area under the curve [AUC] 0.739 and 0.735). C-reactive protein on post-operative day three was an independent predictor of infection. Five-year survival was higher in the non-infected group (70.8%), compared with the infected group (52.1%). The worst survival (40.9%) was identified in patients with organ/space SSI. Post-operative infection and tumor stage III-IV were independent predictors of a worse five-year survival. C-reactive protein on post-operative day three and PCT on post-operative day two may be early predictors of infection after colorectal cancer surgery. Post-operative infections in particular organ/space SSI have a negative impact on long-term survival.

  3. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, R. Charles, E-mail: rnichols@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph A. [Division of Urology, University of Florida Shands Hospital, Jacksonville, FL (United States); Mendenhall, Nancy P. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-03-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  4. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    International Nuclear Information System (INIS)

    Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

    2012-01-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  5. High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer

    International Nuclear Information System (INIS)

    MacLeod, Craig; Fowler, Allan; Duval, Peter; D'Costa, Ieta; Dalrymple, Chris; Firth, Ian; Elliott, Peter; Atkinson, Ken; Carter, Jonathan

    1998-01-01

    Purpose: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. Methods and Materials: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. Results: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. Conclusion: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence

  6. Post-traumatic stress disorder in mothers of children who have undergone cancer surgery.

    Science.gov (United States)

    Karadeniz Cerit, Kıvılcım; Cerit, Cem; Nart, Ömer; Eker, Nurşah; Kıyan, Gürsu; Dağlı, Tolga; Ekingen, Gülşen; Tokuç, Gülnur; Karaca, Ömer; Çorapçıoğlu, Funda

    2017-09-01

    The aim of this study was to investigate the rate of post-traumatic stress disorder (PTSD) and associated risk factors among mothers of children who underwent cancer surgery. This cross-sectional, multi-center study included a total of 60 mothers whose children underwent major thoraco-abdominal surgery and were under follow up in the outpatient setting between February 2016 and May 2016. Clinical Data Form, Hospital Anxiety and Depression Scale (HADS), and Clinician-Administered PTSD scale were used. Of all participants, 13 (21.7%) were diagnosed with PTSD. These mothers had shorter duration of marriage, longer duration of hospital stay after surgery, and higher HADS scores, compared with the others without PTSD. Thoughts of guilt such as "I am being punished or tested" were more frequent in mothers with PTSD. Insomnia, irritability, concentration problems, and psychological reactivity were the most common symptoms. Post-traumatic stress disorder is a severe disorder that may worsen the daily functioning of mothers and may also have an unfavorable effect on child. It is therefore of utmost importance for clinicians to recognize PTSD and the associated risk factors in order to guide these parents. © 2017 Japan Pediatric Society.

  7. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer: A Population-based Study.

    Science.gov (United States)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine; Pedersen, Lars; Vyberg, Mogens; Koeppe, Erika; Crockett, Seth D; Hamilton, Stanley R; Sørensen, Henrik T; Baron, John A

    2016-11-01

    Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy. We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%). In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and

  8. 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

  9. Radiation induced cancer risk estimation for contralateral breast in 3D conformal treatments of post mastectomy cancer patients: based on OED

    International Nuclear Information System (INIS)

    Hemalatha, A.; Athiyaman, M.; Kumar, H.S.; Chougule, Arun

    2016-01-01

    A global comparison of breast cancer in India with other countries like US/China in 2012 gave a data that collectively the above countries including India account for almost one third of global breast cancer burden. According to this report for every two women newly diagnosed with breast cancer in India, one lady is dying of it. The curative radiotherapy for breast cancer treatment associated with scattered and leakage radiation exposure to critical organs like contralateral breast, lung etc. Radiation is one of the well known carcinogen of breast due its high radiosensititvity. The study done by Stovall et al concluded that the contralateral breast cancer risk is elevated for breast cancer patients of age less than 40 years if dose to health breast is greater than 1 Gy. So its necessary to evaluate dose to Contralateral Breast (ClB) for breast cancer patients for more than 1 Gy. The aim of this study is to compare the risks of secondary breast cancer from conventional wedge field and forward IMRT technique using the concept of OED-Organ Equivalent Dose/for chest wall irradiation of post mastectomy breast cancer patients

  10. Awareness of cervical cancer risk factors and symptoms: cross-sectional community survey in post-conflict northern Uganda.

    Science.gov (United States)

    Mwaka, Amos D; Orach, Christopher G; Were, Edward M; Lyratzopoulos, Georgios; Wabinga, Henry; Roland, Martin

    2016-08-01

    Lack of awareness of risk factors and symptoms for cancer may lead to late diagnosis and poor prognosis. We assessed community awareness about cervical cancer risk factors and symptoms and perceptions about prevention and cure of cervical cancer in order to contribute data to inform interventions to improve cervical cancer survival. Cross-sectional population-based survey. We conducted this study in Gulu, a post-conflict district in Uganda in 2012. The sample included 448 persons aged 18 years and above, selected through a multi-stage stratified cluster sampling process. We collected data using a pretested structured questionnaire. Logistic regressions were used to determine magnitudes of associations between socio-demographic and outcome variables. Most participants (444/448) had heard about cervical cancer. Known risk factors including multiple sexual partners, human papillomavirus infection, and early onset of sexual activity, were recognized by 88%, 82%, and 78% of respondents respectively. 63% of participants believed that prolonged use of family planning pills and injections caused cervical cancer. The majority of participants recognized symptoms of cervical cancer including inter-menstrual bleeding (85%), post-menopausal bleeding (84%), and offensive vaginal discharge (83%). 70% of participants believed that cervical cancer is preventable and 92% believed that it could be cured if diagnosed at an early stage. Recognition of cervical cancer risk factors and symptoms was high among study participants. Targeted interventions including increasing availability of HPV vaccination, population-based cervical screening and diagnostic services can translate high awareness into actual benefits. © 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

  11. A targeted enzyme approach to sensitization of tyrosine kinase inhibitor-resistant breast cancer cells.

    Science.gov (United States)

    Giordano, Courtney R; Mueller, Kelly L; Terlecky, Laura J; Krentz, Kendra A; Bollig-Fischer, Aliccia; Terlecky, Stanley R; Boerner, Julie L

    2012-10-01

    Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of potential use in patients with breast cancer. Unfortunately, in clinical studies, gefitinib is often ineffective indicating that resistance to EGFR inhibitors may be a common occurrence in cancer of the breast. EGFR has been shown to be overexpressed in breast cancer, and in particular remains hyperphosphorylated in cell lines such as MDA-MB-468 that are resistant to EGFR inhibitors. Here, we investigate the cause of this sustained phosphorylation and the molecular basis for the ineffectiveness of gefitinib. We show that reactive oxygen species (ROS), known to damage cellular macromolecules and to modulate signaling cascades in a variety of human diseases including cancers, appear to play a critical role in mediating EGFR TKI-resistance. Furthermore, elimination of these ROS through use of a cell-penetrating catalase derivative sensitizes the cells to gefitinib. These results suggest a new approach for the treatment of TKI-resistant breast cancer patients specifically, the targeting of ROS and attendant downstream oxidative stress and their effects on signaling cascades. Copyright © 2012. Published by Elsevier Inc.

  12. Post-colonoscopy colorectal cancer rate in the era of high-definition colonoscopy.

    Science.gov (United States)

    Iwatate, Mineo; Kitagawa, Tomoyuki; Katayama, Yasumi; Tokutomi, Naohiko; Ban, Shinichi; Hattori, Santa; Hasuike, Noriaki; Sano, Wataru; Sano, Yasushi; Tamano, Masaya

    2017-11-14

    To investigate the post-colonoscopy colorectal cancer (PCCRC) rate for high-definition (HD) colonoscopy compared with that for standard-definition colonoscopy reported previously. Using medical records at Sano Hospital (SH) and Dokkyo Medical University Koshigaya Hospital (DMUKH), we retrospectively obtained data on consecutive patients diagnosed as having CRC between January 2010 and December 2015. The definition of PCCRC was diagnosis of CRC between 7 and 36 mo after initial high-definition colonoscopy that had detected no cancer, and patients were divided into a PCCRC group and a non-PCCRC group. The primary outcome was the rate of PCCRC for HD colonoscopy. The secondary outcomes were factors associated with PCCRC and possible reason for occurrence of early and advanced PCCRC. Among 892 CRC patients, 11 were diagnosed as having PCCRC and 881 had non-PCCRC. The PCCRC rate was 1.7% (8/471) at SH and 0.7% (3/421) at DMUKH. In comparison with the non-PCCRC group, the PCCRC group had a significantly higher preponderance of smaller tumors (39 mm vs 19 mm, P = 0.002), a shallower invasion depth (T1 rate, 25.4% vs 63.6%, P = 0.01), a non-polypoid macroscopic appearance (39.0% vs 85.7%, P = 0.02) and an earlier stage (59.7% vs 90.9%, P = 0.03). Possible reasons for PCCRC were "missed or new" in 9 patients (82%), "incomplete resection" in 1 (9%), and "inadequate examination'" in 1 (9%). Among 9 "missed or new" PCCRC, the leading cause was non-polypoid shape for early PCCRC and blinded location for advanced PCCRC. The PCCRC rate for HD colonoscopy was 0.7%-1.7%, being lower than that for standard-definition colonoscopy (1.8%-9.0%) reported previously employing the same methodology.

  13. Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors.

    Science.gov (United States)

    Cespedes Feliciano, Elizabeth M; Kwan, Marilyn L; Kushi, Lawrence H; Weltzien, Erin K; Castillo, Adrienne L; Caan, Bette J

    2017-04-01

    Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery. We studied Stage I-III breast cancer survivors 18 to  diagnosis and weight and waist circumference (WC) around 24 months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n = 3109) and post-diagnosis WC (n = 1898) and weight change (n = 1903, stable, ±5 to  diagnosis, 25% of women gained and 14% lost ≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28 years, 915 women developed CVD. BMI 25-30-kg/m 2 (vs. BMI diagnosis weight change had no association with CVD. Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.

  14. Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer

    International Nuclear Information System (INIS)

    Pearcey, R.G.; Petereit, D.G.

    2000-01-01

    This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. The world literature was reviewed and thirteen series were analyzed representing 1800 cases. A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy 3 (LQED = 60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy 10 or LQED = 30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates. (author)

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

    International Nuclear Information System (INIS)

    Mianji, Fereidoun A.; Karimi Diba, Jila; Babakhani, Asad

    2015-01-01

    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)

  16. Post-Translational Modifications of H2A Histone Variants and Their Role in Cancer

    Directory of Open Access Journals (Sweden)

    David Corujo

    2018-02-01

    Full Text Available Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core. These accessible tails are the preferential target sites for a large number of post-translational modifications (PTMs. While some PTMs are shared between replication-coupled H2A and H2A variants, many modifications are limited to a specific histone variant. The present review focuses on the H2A variants H2A.Z, H2A.X, and macroH2A, and summarizes their functions in chromatin and how these are linked to cancer development and progression. H2A.Z primarily acts as an oncogene and macroH2A and H2A.X as tumour suppressors. We further focus on the regulation by PTMs, which helps to understand a degree of context dependency.

  17. Preoperative body size and composition, habitual diet, and post-operative complications in elective colorectal cancer patients in Norway.

    Science.gov (United States)

    Berstad, P; Haugum, B; Helgeland, M; Bukholm, I; Almendingen, K

    2013-08-01

    Both malnutrition and obesity are related to worsened post-operative outcomes after colorectal surgery. Obese cancer patients may be malnourished as a result of short-term weight loss. The present study aimed to evaluate preoperative nutritional status, body composition and dietary intake related to post-operative complications (POC) and post-operative hospital days (POHD) in elective colorectal cancer (CRC) patients. Anthropometry, body composition measured by bioelectric spectroscopy and dietary habits assessed by a validated food-frequency questionnaire were examined in 100 newly-diagnosed CRC patients. Data from 30-day POC and POHD were collected from medical records. Nonparametric and chi-squared tests and logistic regression were used to analyse associations between body and dietary variables and post-operative outcome. Twenty-nine patients had at least one POC. The median POHD was six. Body size and composition measures and short-term weight loss were no different between patients with and without POC, or between patients with POHD body size, body composition and short-term weight loss were not related to 30-day post-operative outcomes in CRC patients. A high content of marine n-3 PUFA in preoperative habitual diets may protect against POC after CRC surgery. © 2012 The Authors Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

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

    Science.gov (United States)

    2017-06-07

    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

  19. Post operative high dose rate intravaginal irradiation in endometrial cancer: a safe and effective outpatient treatment

    International Nuclear Information System (INIS)

    Chen, Peter; Gibbons, Susan; Vicini, Frank; Weiner, Sheldon; Dmuchowski, Carl; Mele, Beth; Brabbins, Donald; Jennings, John; Gustafson, Gary; Martinez, Alvaro

    1995-01-01

    Purpose: We reviewed our experience with out patient high dose rate (HDR) intravaginal irradiation given post-operatively in endometrial cancer to assess local control, survival, and toxicity when used alone or in combination with external beam irradiation. Methods and Materials: From (12(88)) to (12(92)), 78 patients underwent TAH/BSO and received post-operative HDR intravaginal irradiation for endometrial cancer. Pathologic stage distribution was IB/IC: 56%, II: 22%, III: 22%. Adjuvant therapy was given in one of three schemes: HDR vaginal radiation alone (6 weekly fractions of 500 cGy prescribed 5 mm from the applicator surface treating the upper 4 cm of the vagina), pelvic irradiation with vaginal HDR (500 cGy x 4 weekly fractions) or whole abdomen/pelvic irradiation (WAPI) with vaginal HDR treatment (500 cGy x 3 weekly fractions). Prior to the first HDR vaginal treatment, a simulation with placement of vaginal apex metallic markers was performed to assure proper positioning of the intravaginal cylinders. Pelvic midline blocking was designed from the HDR intravaginal simulation films. The 55 patients who underwent combined external beam irradiation/brachytherapy received a median dose to the pelvis of 5040 cGy (range 25.2-51.6 Gy), and a median total vaginal dose of 5060 cGy (range 30.0-57.6 Gy). Results: Median follow-up is 37 months (range 6-73 months). Local control (vaginally) is 98.7%. The one vaginal failure was in the distal vagina, outside the treatment volume. All other failures (4) were distant with the vagina controlled [3 intra-abdominal and one bone/intra-abdominal]. For stages I and II, the disease free survival is 92.8%. For stage III the disease free survival is 86.5%. Median overall time to failure is 14.3 months (range 8.5-18.6 months). In terms of acute toxicity, no grade 3-4 acute toxicity of the vagina or bladder was seen. However, 9% acute GI toxicity was encountered. Chronic grade 1-2 toxicities included: vaginal 21.8% (foreshortening and

  20. Gefitinib, an EGFR Tyrosine Kinase inhibitor, Prevents Smoke-Mediated Ciliated Airway Epithelial Cell Loss and Promotes Their Recovery.

    Directory of Open Access Journals (Sweden)

    Monica Valencia-Gattas

    Full Text Available Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.

  1. 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...... 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...

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

    International Nuclear Information System (INIS)

    Choi, Hyun Su; Kim, Sung Hoon; Park, Sonya Youngju; Park, Hye Lim; Seo, Ye Young; Choi, Woo Hee

    2014-01-01

    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. A qualitative synthesis of trials promoting physical activity behaviour change among post-treatment breast cancer survivors.

    Science.gov (United States)

    Short, Camille E; James, Erica L; Stacey, Fiona; Plotnikoff, Ronald C

    2013-12-01

    Health outcome trials have provided strong evidence that participating in regular physical activity can improve the quality of life and health of post-treatment breast cancer survivors. Focus is now needed on how to promote changes in physical activity behaviour among this group. This systematic review examines the efficacy of behavioural interventions for promoting physical activity among post-treatment breast cancer survivors. Behavioural intervention studies published up until July 2012 were identified through a systematic search of two databases: MEDLINE and CINAHL, and by searching reference lists of relevant publications and scanning citation libraries of project staff. Eight out of the ten identified studies reported positive intervention effects on aerobic physical activity behaviour, ranging from during the intervention period to 6 months post-intervention. Only two studies reported intervention effect sizes. The identification of factors related to efficacy was not possible because of the limited number and heterogeneity of studies included, as well as the lack of effect sizes reported. Nonetheless, an examination of the eight studies that did yield significant intervention effects suggests that 12-week interventions employing behaviour change techniques (e.g., self-monitoring and goal setting) derived from a variety of theories and delivered in a variety of settings (i.e., one-on-one, group or home) can be effective at changing the aerobic physical activity behaviour of breast cancer survivors in the mid- to long terms. Behavioural interventions do hold promise for effectively changing physical activity behaviour among breast cancer survivors. However, future research is needed to address the lack of studies exploring long-term intervention effects, mediators of intervention effects and interventions promoting resistance-training activity, and to address issues impacting on validity, such as the limited use of objective physical activity measures and

  4. Multi-center evaluation of post-operative morbidity and mortality after optimal cytoreductive surgery for advanced ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Arash Rafii

    Full Text Available PURPOSE: While optimal cytoreduction is the standard of care for advanced ovarian cancer, the related post-operative morbidity has not been clearly documented outside pioneering centers. Indeed most of the studies are monocentric with inclusions over several years inducing heterogeneity in techniques and goals of surgery. We assessed the morbidity of optimal cytoreduction surgery for advanced ovarian cancer within a short inclusion period in 6 referral centers dedicated to achieve complete cytoreduction. PATIENTS AND METHODS: The 30 last optimal debulking surgeries of 6 cancer centers were included. Inclusion criteria included: stage IIIc- IV ovarian cancer and optimal surgery performed at the site of inclusion. All post-operative complications within 30 days of surgery were recorded and graded using the Memorial secondary events grading system. Student-t, Chi2 and non-parametric statistical tests were performed. RESULTS: 180 patients were included. There was no demographic differences between the centers. 63 patients underwent surgery including intestinal resections (58 recto-sigmoid resection, 24 diaphragmatic resections, 17 splenectomies. 61 patients presented complications; One patient died post-operatively. Major (grade 3-5 complications requiring subsequent surgeries occurred in 21 patients (11.5%. 76% of patients with a major complication had undergone an ultraradical surgery (P = 0.004. CONCLUSION: While ultraradical surgery may result in complete resection of peritoneal disease in advanced ovarian cancer, the associated complication rate is not negligible. Patients should be carefully evaluated and the timing of their surgery optimized in order to avoid major complications.

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

    International Nuclear Information System (INIS)

    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 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

  6. Efficacy of Mindfulness-Based Cognitive Therapy on Late Post-Treatment Pain in Women Treated for Primary Breast Cancer: A Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Johannsen, Maja; O Connor, Maja; OToole, Mia Skytte

    2016-01-01

    PURPOSE: To assess the efficacy of mindfulness-based cognitive therapy (MBCT) for late post-treatment pain in women treated for primary breast cancer. METHODS: A randomized wait list-controlled trial was conducted with 129 women treated for breast cancer reporting post-treatment pain (score ≥ 3...... pain rehabilitation strategy for women treated for breast cancer. In addition, the effect on neuropathic pain, a pain type reported by women treated for breast cancer, further suggests the potential of MBCT but should be considered preliminary....

  7. 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)

    Kang, Khong Bee; Zhu Congju; Wong Yinling; Gao Qiuhan; Ty, Albert; Wong, Meng Cheong

    2012-01-01

    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, γ-H 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, γ-H 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 2 /M arrest and increased γ-H 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 γ-H 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 resistant to irradiation

  8. 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.

    Science.gov (United States)

    Kang, Khong Bee; Zhu, Congju; Wong, Yin Ling; Gao, Qiuhan; Ty, Albert; Wong, Meng Cheong

    2012-05-01

    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. Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H(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, γ-H(2)AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. 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(2)/M arrest and increased γ-H(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 γ-H(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. Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G(2)/M arrest, and DNA DSBs, compared with nonstem

  9. 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

  10. 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.

  11. Ph.D. Post-Doctoral Training Program in Breast Cancer Research

    National Research Council Canada - National Science Library

    Edwards, Dean

    2002-01-01

    .... The curriculum of the Breast Cancer Training Program extends beyond that of the normal Ph.D. requirements to include didactic classroom teaching, journal clubs, seminars, workshops and mini-symposiums on relevant topics in breast cancer...

  12. Ph.D. Post-Doctoral Training Program in Breast Cancer Research

    National Research Council Canada - National Science Library

    Edwards, Dean

    2001-01-01

    .... The curriculum of the Breast Cancer Training Program extends beyond that of the normal Ph.D. requirements to include didactic classroom teaching, journal clubs, seminars, workshops and mini-symposiums on relevant topics in breast cancer...

  13. Ph.D. Post-Doctoral Training Program in Breast Cancer Research

    National Research Council Canada - National Science Library

    Edwards, Dean

    2004-01-01

    .... The curriculum of the Breast Cancer Training Program extends beyond that of the normal Ph.D. requirements to include didactic classroom teaching, journal clubs, seminars, workshops and mini-symposiums on relevant topics in breast cancer...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Tae; Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1990-02-15

    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.

  15. Lifetime moderate-to-vigorous physical activity and ER/PR/HER-defined post-menopausal breast cancer risk.

    Science.gov (United States)

    Shi, Joy; Kobayashi, Lindsay C; Grundy, Anne; Richardson, Harriet; SenGupta, Sandip K; Lohrisch, Caroline A; Spinelli, John J; Aronson, Kristan J

    2017-08-01

    To assess the relationship of moderate-to-vigorous physical activity (MVPA) in leisure-time, household, and occupational domains across the total lifetime and in four age periods with breast cancer risk, as defined by estrogen receptor (ER)/progesterone receptor (PR) status and ER/PR/human epidermal growth factor-2 (HER2) status, among post-menopausal women. Data were from 692 women with incident breast cancer and 644 controls in the Canadian Breast Cancer Study, a case-control study of women aged 40-80 years in British Columbia and Ontario. Mean metabolic equivalent (MET)-hours/week for questionnaire-assessed leisure-time, household, and occupational MVPA were calculated for the total lifetime and four age periods (12-17, 18-34, 45-49, and ≥50 years). Odds ratios (ORs) for the relationships between domain-specific MVPA at each lifetime period and risks of ER/PR-defined and ER/PR/HER2-defined breast cancers were estimated using polytomous logistic regression. Trend tests for dose-response relationships were calculated for the ORs across increasing tertiles of mean MET-hours/week of MVPA. Total lifetime leisure-time MVPA was associated with reduced risk of ER-/PR- breast cancer in a dose-response fashion (p trend  = 0.014). In contrast, total lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer (p trend  trends were observed when stratified by age period. Lifetime leisure-time MVPA appeared to be associated with reduced risk of ER-/PR-/HER2- breast cancers and lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer, regardless of HER2 status.

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

    Science.gov (United States)

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

    2016-03-29

    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 cancer in an Afghan man who is an asylum seeker of Asian ethnic origin. A focused ethnographic case study and in-depth interview was used to gain qualitative data and insight into the personal experiences of a male Afghan asylum seeker, age unknown (estimated to be in his 30s), with post-traumatic stress disorder who was electively admitted into hospital for the investigation of a suspicious lump in his left breast, which was subsequently found to be breast cancer. He was extremely reluctant to accept a breast cancer diagnosis and initially would not consent to any treatment, preferring to seek further opinion. During consultation with various members of the breast team he continually declined to accept the diagnosis and felt there was an error in the investigative protocol. Through the involvement of a Muslim nurse, fluent in Urdu and knowledgeable of the Afghan culture and religious background, we learned about his experiences and feelings; he opened up to her about his experiences in Afghanistan, detailing his experiences of trauma as a result of war, and disclosing that he had been diagnosed as having post-traumatic stress disorder by his physician. He saw breast cancer as a "woman's disease" which deeply affected his feelings of masculinity and left him feeling vulnerable. While sensitivity is undoubtedly required when diagnosing gender-biased conditions such as breast cancer in men, our experience showed this is exacerbated in ethnic minority groups where language barriers often exist

  17. Value of the post-operative CT in predicting delayed flap failures following head and neck cancer surgery

    International Nuclear Information System (INIS)

    Kim, Bitna; Yoon, Dae Young; Seo, Young Lan; Park, Min Woo; Kwon, Kee Hwan; Rho, Young Soo; Chung, Chul Hoon

    2017-01-01

    To identify post-operative computed tomography (CT) findings associated with delayed flap failures following head and neck cancer surgery. We retrospectively reviewed 60 patients who underwent flap reconstruction after head and neck cancer surgery and post-operative (3–14 days) contrast-enhanced CT scans for suspected complications. Patients were divided into two groups: delayed flap failure patients (patients required flap revision) (n = 18) and flap success patients (n = 42). Clinical data (age, sex, T-stage, type of flap, and time interval between reconstruction surgery and CT) and post-operative CT findings of flap status (maximum dimension of the flap, intra- or peri-flap fluid collection and intra- or peri-flap air collection, fat infiltration within the flap, fistula to adjacent aerodigestive tract or skin, and enhanced vascular pedicle) were assessed and compared between the two groups. CT findings showed that the following flap anomalies were observed more frequently in the delayed flap failure group than in the flap success group: intra- or peri-flap fluid collection > 4 cm (61.1% vs. 23.8%, p 2 cm (61.1% vs. 2.4%, p < 0.001), and fistula to adjacent aerodigestive tract or skin (44.4% vs. 0%, p < 0.001). The maximum dimension of the flap, fat infiltration within the flap, and enhanced vascular pedicle were not associated with delayed flap failures. A large amount of fluid or air collection and fistula are the CT findings that were associated with delayed flap failures in patients with suspected post-operative complications after head and neck cancer surgery

  18. Clinical Utility of SPECT/CT Imaging Post-Radioiodine Therapy: Does It Enhance Patient Management in Thyroid Cancer?

    Science.gov (United States)

    Hassan, Fahim U; Mohan, Hosahalli K

    2015-12-01

    The aim of this study was to evaluate post-therapy iodine-131 single-photon emission computed tomography/computed tomography ((131)I-SPECT/CT) imaging in comparison to conventional planar (131)I whole-body imaging, and to assess its clinical impact on the management of patients. We retrospectively reviewed planar (131)I whole-body and (131)I-SPECT/CT imaging findings in 67 patients who underwent (131)I therapy for thyroid cancer. Two nuclear medicine physicians reviewed the scans independently. The foci of increased tracer uptake were identified in the neck, thorax and elsewhere. Within the neck, the foci of (131)I-increased uptake were graded qualitatively as probable or definite uptake in thyroid remnants and probable or definite uptake in the lymph nodes. Serum thyroglobulin level, histopathology and other imaging findings served as the reference standard. Of the 67 patients, 57 (85%) had radioiodine avid disease and 10 (15%) demonstrated non-radioiodine avid disease. Overall, post-therapy (131)I-SPECT/CT downstaged lymph node staging in 10 patients and upstaged it in 4 patients. This translated into a change of management for 9/57 (16%) patients with radioiodine avid disease. A change of management was observed in 5/10 patients with non-radioiodine avid disease confirmed in the post-(131)I-SPECT/CT study. Additionally, clinically significant findings such as incidental lung cancer, symptomatic pleural effusion and consolidation were also diagnosed in both groups of patients. In patients with thyroid cancer, (131)I-SPECT/CT is a valuable addition to standard post-therapy planar imaging. SPECT/CT also improved diagnostic confidence and provided crucial clinical information leading to change of management for a significant number of these patients.

  19. Value of the post-operative CT in predicting delayed flap failures following head and neck cancer surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bitna; Yoon, Dae Young; Seo, Young Lan; Park, Min Woo; Kwon, Kee Hwan; Rho, Young Soo; Chung, Chul Hoon [Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To identify post-operative computed tomography (CT) findings associated with delayed flap failures following head and neck cancer surgery. We retrospectively reviewed 60 patients who underwent flap reconstruction after head and neck cancer surgery and post-operative (3–14 days) contrast-enhanced CT scans for suspected complications. Patients were divided into two groups: delayed flap failure patients (patients required flap revision) (n = 18) and flap success patients (n = 42). Clinical data (age, sex, T-stage, type of flap, and time interval between reconstruction surgery and CT) and post-operative CT findings of flap status (maximum dimension of the flap, intra- or peri-flap fluid collection and intra- or peri-flap air collection, fat infiltration within the flap, fistula to adjacent aerodigestive tract or skin, and enhanced vascular pedicle) were assessed and compared between the two groups. CT findings showed that the following flap anomalies were observed more frequently in the delayed flap failure group than in the flap success group: intra- or peri-flap fluid collection > 4 cm (61.1% vs. 23.8%, p < 0.05), intra- or peri-flap air collection > 2 cm (61.1% vs. 2.4%, p < 0.001), and fistula to adjacent aerodigestive tract or skin (44.4% vs. 0%, p < 0.001). The maximum dimension of the flap, fat infiltration within the flap, and enhanced vascular pedicle were not associated with delayed flap failures. A large amount of fluid or air collection and fistula are the CT findings that were associated with delayed flap failures in patients with suspected post-operative complications after head and neck cancer surgery.

  20. Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments.

    Directory of Open Access Journals (Sweden)

    Debby D Wang

    Full Text Available EGFR mutation-induced drug resistance has become a major threat to the treatment of non-small-cell lung carcinoma. Essentially, the resistance mechanism involves modifications of the intracellular signaling pathways. In our work, we separately investigated the EGFR and ErbB-3 heterodimerization, regarded as the origin of intracellular signaling pathways. On one hand, we combined the molecular interaction in EGFR heterodimerization with that between the EGFR tyrosine kinase and its inhibitor. For 168 clinical subjects, we characterized their corresponding EGFR mutations using molecular interactions, with three potential dimerization partners (ErbB-2, IGF-1R and c-Met of EGFR and two of its small molecule inhibitors (gefitinib and erlotinib. Based on molecular dynamics simulations and structural analysis, we modeled these mutant-partner or mutant-inhibitor interactions using binding free energy and its components. As a consequence, the mutant-partner interactions are amplified for mutants L858R and L858R_T790M, compared to the wild type EGFR. Mutant delL747_P753insS represents the largest difference between the mutant-IGF-1R interaction and the mutant-inhibitor interaction, which explains the shorter progression-free survival of an inhibitor to this mutant type. Besides, feature sets including different energy components were constructed, and efficient regression trees were applied to map these features to the progression-free survival of an inhibitor. On the other hand, we comparably examined the interactions between ErbB-3 and its partners (EGFR mutants, IGF-1R, ErbB-2 and c-Met. Compared to others, c-Met shows a remarkably-strong binding with ErbB-3, implying its significant role in regulating ErbB-3 signaling. Moreover, EGFR mutants corresponding to poor clinical outcomes, such as L858R_T790M, possess lower binding affinities with ErbB-3 than c-Met does. This may promote the communication between ErbB-3 and c-Met in these cancer cells. The

  1. Clinical profile and post-operative lifestyle changes in cancer and non-cancer patients with ostomy

    Science.gov (United States)

    Anaraki, Fakhryalsadat; Vafaie, Mohamad; Behboo, Roobic; Maghsoodi, Nakisa; Esmaeilpour, Sahar

    2012-01-01

    Aim The aim of this was to investigate some clinical profiles and lifestyle changes in stoma patients. Background Stoma patients experienced multiple complications due to their ostomy formation. Patients and methods A cross-sectional study performed on 102 random samples of stoma patients. Any patient with adequate physical and mental capability to participate and having had an ostomy in place for at least 3 months was eligible to enter the study. Participants asked to answer study questions concerning age, sex, type of stoma, having permanent or temporary ostomy, underlying cause of stoma formation, type of cancers cause of stoma. Patient also questioned about some lifestyle changes because of stoma including: changing diet, sexual satisfaction (if sexually active after stoma formation), sense of depression, changing job, change clothing style. Results Colostomy was the most common type of stoma followed by ileostomy and urostomy. In 80.4% of patients under study the stoma was permanent. Most patients had a stoma because of cancer (77.5%), with colon cancer (41.2%) being the most common malignant diagnosis. The mean age of cancer patients (56.1±10.9) with stoma was significantly higher than non-cancer patients (44.7±12.9) (p ostomy. Conclusion In conclusion, stoma formation can caused multiple problems for both cancer and non-cancer patients. Counseling of patient is an important component of care that could help stoma patients to adjust with new situations. PMID:24834234

  2. Common breast cancer risk variants in the post-COGS era: a comprehensive review

    OpenAIRE

    Maxwell, Kara N; Nathanson, Katherine L

    2013-01-01

    Breast cancer has a strong heritable component, with approximately 15% of cases exhibiting a family history of the disease. Mutations in genes such as BRCA1, BRCA2 and TP53 lead to autosomal dominant inherited cancer susceptibility and confer a high lifetime risk of breast cancers. Identification of mutations in these genes through clinical genetic testing enables patients to undergo screening and prevention strategies, some of which provide overall survival benefit. In addition, a number of ...

  3. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  4. Common breast cancer risk variants in the post-COGS era: a comprehensive review.

    Science.gov (United States)

    Maxwell, Kara N; Nathanson, Katherine L

    2013-12-20

    Breast cancer has a strong heritable component, with approximately 15% of cases exhibiting a family history of the disease. Mutations in genes such as BRCA1, BRCA2 and TP53 lead to autosomal dominant inherited cancer susceptibility and confer a high lifetime risk of breast cancers. Identification of mutations in these genes through clinical genetic testing enables patients to undergo screening and prevention strategies, some of which provide overall survival benefit. In addition, a number of mutant alleles have been identified in genes such as CHEK2, PALB2, ATM and BRIP1, which often display incomplete penetrance and confer moderate lifetime risks of breast cancer. Studies are underway to determine how to use the identification of mutations in these genes to guide clinical practice. Altogether, however, mutations in high and moderate penetrance genes probably account for approximately 25% of familial breast cancer risk; the remainder may be due to mutations in as yet unidentified genes or lower penetrance variants. Common low penetrance alleles, which have been mainly identified through genome-wide association studies (GWAS), are generally present at 10 to 50% population frequencies and confer less than 1.5-fold increases in breast cancer risk. A number of single nucleotide polymorphisms (SNPs) have been identified and risk associations extensively replicated in populations of European ancestry, the number of which has substantially increased as a result of GWAS performed by the Collaborative Oncological Gene-environment Study consortium. It is now estimated that 28% of familial breast cancer risk is explained by common breast cancer susceptibility loci. In some cases, SNP associations may be specific to different subsets of women with breast cancer, as defined by ethnicity or estrogen receptor status. Although not yet clinically established, it is hoped that identification of common risk variants may eventually allow identification of women at higher risk of

  5. Management of side effects during and post-treatment in breast cancer survivors.

    Science.gov (United States)

    Palesh, Oxana; Scheiber, Caroline; Kesler, Shelli; Mustian, Karen; Koopman, Cheryl; Schapira, Lidia

    2018-03-01

    Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are commonly experienced symptoms that share psychological and physical manifestations. One or more of these symptoms will affect nearly all patients at some point during their course of treatment or survivorship. These side effects are burdensome and reduce patients' quality of life well beyond their cancer diagnosis and associated care treatments. Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are likely to have multiple etiologies that make it difficult to identify the most effective method to manage them. In this review, we summarized the information on cancer-related fatigue, insomnia, and cancer-related cognitive impairment incidence and prevalence among breast cancer patients and survivors as well as recent research findings on pharmaceutical, psychological, and exercise interventions that have shown effectiveness in the treatment of these side effects. Our review revealed that most current pharmaceutical interventions tend to ameliorate symptoms only temporarily without addressing the underlying causes. Exercise and behavioral interventions are consistently more effective at managing chronic symptoms and possibly address an underlying etiology. Future research is needed to investigate effective interventions that can be delivered directly in clinic to a large portion of patients and survivors. © 2017 Wiley Periodicals, Inc.

  6. Post-surgical management of patients with breast cancer at Kenyatta ...

    African Journals Online (AJOL)

    Conclusion: Chemotherapy is grossly underutilized in the treatment of breast cancer at the Kenyatta National Hospital, and radiotherapy is also underutilized. Follow-up durations are dismal and if this is used as a surrogate measure for survival then survival durations for breast cancer patients are also dismal at the Kenyatta ...

  7. Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer

    International Nuclear Information System (INIS)

    Saga, Tsuneo; Higashi, Tatsuya; Ishimori, Takayoshi

    2003-01-01

    The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated. Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient. In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient's follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses. These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient. (author)

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

    International Nuclear Information System (INIS)

    Lue, B.-H.; Huang, T.-S.; Chen, H.-J.

    2008-01-01

    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

  9. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Science.gov (United States)

    Wiley, Teresa S.; Haraldsen, Jason T.

    2012-03-01

    We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  10. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Directory of Open Access Journals (Sweden)

    Teresa S. Wiley

    2012-03-01

    Full Text Available We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  11. Reduction of recurrence in non-muscle invasive bladder cancer using photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg

    2013-01-01

    (TUR-B), and one single instillation of 40 mg Mitomycin C (MMC) within 24 hours post-TUR-B were introduced at our institution by March 2008. For the study, patients were identified retrospectively using procedure codes for TUR-B and cystoscopy with biopsy and fulguration. Patients with muscle......-invasive bladder cancer were excluded. 190 consecutive patients, treated between 03-01-2008 and 28-02-2010, were included into the intervention group, while 216 patients, treated between 03-01-2006 and 29-02-2008, served as controls. Procedures and pathology results were registered. The groups were comparable...

  12. Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

    Science.gov (United States)

    Shek, L L; Godolphin, W; Spinelli, J J

    1987-12-01

    The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

  13. Post-diagnostic dietary changes in prostate cancer: associations with patients' wellbeing and the perceptions of GPs.

    Science.gov (United States)

    Kassianos, A P; Raats, M M; Gage, H

    2017-07-01

    This article aims to investigate associations between perceived control and health-related quality of life (HRQOL) with dietary changes after prostate cancer diagnosis and to explore General Practitioners' (GPs) perceptions on the role of diet in prostate cancer post-diagnosis. Ninety-five prostate cancer patients completed measures of dietary change, one for after diagnosis and another for after therapy. They also scored their HRQOL and perceived control. There were discrepancies in dietary changes reported between a general question (28.4% no dietary changes) and a specific (42.1%-51.5% range of no change for various food items). Most patients initiated healthy changes. Patients who changed their diet after diagnosis had lower cognitive functioning and external locus of control (doctors). Patients who changed their diet after therapy had lower cognitive and emotional functioning, quality of life and external locus of control (doctors). Then, fourty-four GPs responded to an online survey. Their open-ended responses were analysed using Content Analysis. They reported interest in the role of diet in cancer but also lack of relevant knowledge. They were skeptical on providing information. Clinical interventions should consider patients' cognitive ability, their relationship with their health professional and their wellbeing. Also, GPs' confidence to provide dietary advice needs to be addressed. © 2016 John Wiley & Sons Ltd.

  14. A genomic copy number signature predicts radiation exposure in post-Chernobyl breast cancer.

    Science.gov (United States)

    Wilke, Christina M; Braselmann, Herbert; Hess, Julia; Klymenko, Sergiy V; Chumak, Vadim V; Zakhartseva, Liubov M; Bakhanova, Elena V; Walch, Axel K; Selmansberger, Martin; Samaga, Daniel; Weber, Peter; Schneider, Ludmila; Fend, Falko; Bösmüller, Hans C; Zitzelsberger, Horst; Unger, Kristian

    2018-04-16

    Breast cancer is the second leading cause of cancer death among women worldwide and besides life style, age and genetic risk factors, exposure to ionizing radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analyzed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridization analysis (aCGH). Using a stepwise forward-backward selection approach a non-complex CNA signature, that is, less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set (p value < 0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22-11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23-11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA signature that has the potential to allow identification of radiation-associated breast cancer at the individual level. © 2018 UICC.

  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. Cancer-Related Fatigue in Post-Treatment Cancer Survivors: Theory-Based Development of a Web-Based Intervention.

    Science.gov (United States)

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

    2017-07-04

    Cancer-related fatigue (CrF) is the most common and disruptive symptom experienced by cancer survivors. We aimed to develop a theory-based, interactive Web-based intervention designed to facilitate self-management and enhance coping with CrF following cancer treatment. The aim of our study was to outline the rationale, decision-making processes, methods, and findings which led to the development of a Web-based intervention to be tested in a feasibility trial. This paper outlines the process and method of development of the intervention. An extensive review of the literature and qualitative research was conducted to establish a therapeutic approach for this intervention, based on theory. The psychological principles used in the development process are outlined, and we also clarify hypothesized causal mechanisms. We describe decision-making processes involved in the development of the content of the intervention, input from the target patient group and stakeholders, the design of the website features, and the initial user testing of the website. The cocreation of the intervention with the experts and service users allowed the design team to ensure that an acceptable intervention was developed. This evidence-based Web-based program is the first intervention of its kind based on self-regulation model theory, with the primary aim of targeting the representations of fatigue and enhancing self-management of CrF, specifically. This research sought to integrate psychological theory, existing evidence of effective interventions, empirically derived principles of Web design, and the views of potential users into the systematic planning and design of the intervention of an easy-to-use website for cancer survivors. ©Teresa Corbett, Jane C Walsh, AnnMarie Groarke, Rona Moss-Morris, Eimear Morrissey, Brian E McGuire. Originally published in JMIR Cancer (http://cancer.jmir.org), 04.07.2017.

  17. Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor-Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations

    NARCIS (Netherlands)

    Janjigian, Yelena Y.; Smit, Egbert F.; Groen, Harry J. M.; Horn, Leora; Gettinger, Scott; Camidge, D. Ross; Riely, Gregory J.; Wang, Bushi; Fu, Yali; Chand, Vikram K.; Miller, Vincent A.; Pao, William

    EGFR-mutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes

  18. Post-Doctoral Training: Case-Control Analysis of Breast Cancer

    National Research Council Canada - National Science Library

    Cook, Linda

    1998-01-01

    .... Briefly, we found a small elevation in breast cancer risk associated with any use of hair coloring, although exclusive use of one of the four types of hair coloring application was not associated...

  19. Prevention of Post-Radiotherapy Failure in Prostate Cancer by Vitamin D

    National Research Council Canada - National Science Library

    Vijayakumar, Srinivasan

    2005-01-01

    .... We propose to have prostate cancer patients who have already undergone radiation treatment take a non-toxic chemopreventive agent A SYNTHETIC FORM OF VITAMIN D, 1alpha-hydroxyvitamin D5 for two years...

  20. Thyroid cancer post radioactive iodine treatment for hyperthyroidism - case series and review of the literature.

    Science.gov (United States)

    Al Eyadeh, Abdallah A; Al-Sarihin, Khaldon; Etewi, Suzan; Al-Omari, Ahmed; Al-Asa'd, Rania Atallah; Haddad, Fares Halim

    2017-01-01

    To assess the rate of thyroid cancer and mortality rate in a cohort of patients who received RAI¹³¹ treatment for hyperthyroidism and to report the index cases' characteristics and management MATERIAL AND METHODS: A cohort of 264 patients who received RAI¹³¹ treatment for different causes of thyrotoxicosis were followed up over a period of 18 years (1996-2014) by physical exam, radiological evaluation and serial thyroid function tests. During the follow up period, three cases of thyroid cancer were identified. The prevalence of thyroid cancer was 1.136% of cases who received RAI¹³¹. The relative risk was 378.79 (95% CI: 76.8 effect relationship between RAI and thyroid cancer could be established, these cases highlights the importance of life-long surveillance of patients who receive RAI¹³¹.

  1. Body Fat Phenotypes, Sex Hormones and Breast Cancer Risk in Post Manopausal African-American Women

    National Research Council Canada - National Science Library

    Barnett, Junaidah

    2001-01-01

    ... in this country, with very little known about their sex hormone profile. Recent findings have suggested that body fat distribution may be a better marker for breast cancer risk than degree of obesity...

  2. Cohort study of risk factors for breast cancer in post menopausal women.

    Science.gov (United States)

    Hartz, Arthur J; He, Tao

    2013-01-01

    The present study assessed more than 800 potential risk factors to identify new predictors of breast cancer and compare the independence and relative importance of established risk factors. Data were collected by the Women's Health Initiative and included 147,202 women ages 50 to 79 who were enrolled from 1993 to 1998 and followed for 8 years. Analyses performed in 2011 and 2012 used the Cox proportional hazard regression to test the association between more than 800 baseline risk factors and incident breast cancer. Baseline factors independently associated with subsequent breast cancer at the prelative with prostate cancer, colon polyps, smoking, no breast augmentation, and no osteoporosis. Risk factors previously reported that were not independently associated with breast cancer in the present study included socioeconomic status, months of breast feeding, age at first birth, adiposity measures, adult weight gain, timing of initiation of hormone therapy, and several dietary, psychological, and exercise variables. Family history was not found to alter the risk associated with other factors. These results suggest that some risk factors not commonly studied may be important for breast cancer and some frequently cited risk factors may be relatively unimportant or secondary.

  3. 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.

  4. Potentialities of aberrantly methylated circulating DNA for diagnostics and post-treatment follow-up of lung cancer patients.

    Science.gov (United States)

    Ponomaryova, Anastasia A; Rykova, Elena Yu; Cherdyntseva, Nadezda V; Skvortsova, Tatiana E; Dobrodeev, Alexey Yu; Zav'yalov, Alexander A; Bryzgalov, Leonid O; Tuzikov, Sergey A; Vlassov, Valentin V; Laktionov, Pavel P

    2013-09-01

    To date, aberrant DNA methylation has been shown to be one of the most common and early causes of malignant cell transformation and tumors of different localizations, including lung cancer. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA circulating in the blood (cirDNA) is a convenient tumor-associated DNA marker that can be used as a minimally invasive diagnostic test. In the current study, we investigated the methylation status in blood samples of 32 healthy donors and 60 lung cancer patients before and after treatment with neoadjuvant chemotherapy followed by total tumor resection. Using quantitative methylation-specific PCR, we found that the index of methylation (IM), calculated as IM = 100 × [copy number of methylated/(copy number of methylated + unmethylated gene)], for the RASSF1A and RARB2 genes in the cirDNA isolated from blood plasma and cell-surface-bound cirDNA was elevated 2- to 3-fold in lung cancer patients compared with healthy donors. Random forest classification tree model based on these variables combined (RARB2 and RASSF1A IM in both plasma and cell-surface-bound cirDNA) lead to NSCLC patients' and healthy subjects' differentiation with 87% sensitivity and 75% specificity. An association of increased IM values with an advanced stage of non-small-cell lung cancer was found for RARB2 but not for RASSF1A. Chemotherapy and total tumor resection resulted in a significant decrease in the IM for RARB2 and RASSF1A, in both cirDNA fractions, comparable to the IM level of healthy subjects. Importantly, a rise in the IM for RARB2 was detected in patients within the follow-up period, which manifested in disease relapse at 9 months, confirmed with instrumental and pathologic methods. Our data indicate that quantitative analysis of the methylation status of the RARB2 and RASSF1A tumor suppressor genes in both cirDNA fractions is a useful tool for lung cancer diagnostics, evaluation of cancer

  5. Correlation between serum VEGF level and CT perfusion imaging in patients with primary liver cancer pre-and post TACE

    International Nuclear Information System (INIS)

    Jia Zhongzhi; Huang Yuanquan; Feng Yaoliang; Shi Haibin

    2010-01-01

    Objective: To investigate the correlation between serum vascular endothelial growth factor(VEGF) level and CT perfusion parameters in patients with primary liver cancer (PLC) pre-and post-transcatheter arterial chemoembolization (TACE) treatment. Methods: Serum VEGF level was measured and CT perfusion imaging was performed 1 day before and 6 ∼ 8, 32 ∼ 40 days after TACE in 18 patients with PLC. Before and after TACE, the serum VEGF level, the tumor's artery liver perfusion (ALP), the portal vein perfusion (PVP) and the hepatic artery perfusion index (HPI) were measured pre-and post-TACE. The pre-TACE and post-TACE results were compared and statistically analyzed. Results: Based on the therapeutic results, the patients were divided into complete response (CR) group and partial response or stable disease(PR+SD) group. Although no significant difference in serum VEGF level, tumor's ALP, PVP and HPI existed between two groups pre-TACE, there was significant difference in ALP, HPI 6-8 days after TACE (P<0.05). Significant difference in serum VEGF level also existed in CR group (P<0.05), but not in (PR+SD) group, at (32-40) days post-TACE (P=0.221). The serum VEGF level carried a positive correlation with the tumor's ALP and HPI. Conclusion: The serum VEGF level can indirectly reflect the neovascularization of the tumor, while the CTPI can directly and quantitatively reflect the hemodynamic changes of the tumor post-TACE. Moreover, a positive correlation exists between serum VEGF level and ALP, HPI. Therefore, the determination of serum VEGF level together with CTPI is very useful in both evaluating TACE efficacy and making therapeutic schedule. (authors)

  6. Peptide hormones and lung cancer.

    Science.gov (United States)

    Moody, T W

    2006-03-01

    Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.

  7. Covered self-expandable metallic stent placement for a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer

    International Nuclear Information System (INIS)

    Lee, Woon Ha; Jung, Gyoo Sik; Kim, Kyu Jong; Lee, Sang Ho; Ko, Ji Ho; Jeong, Kyung Soon

    2007-01-01

    To evaluate the technical feasibility and clinical effectiveness of stent placement for the treatment of a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer. Under fluoroscopic guidance, one or two covered stents were placed in 20 consecutive patients (age range, 44-75 years) with an anastomotic stricture due to a recurrent gastric malignancy. Before stent placement, all patients had severe nausea and recurrent vomiting after ingestion. Stent placement was technically successful for all patients, and no procedural complications occurred. After stent placement, 18 of 20 (90.0%) patients were able to ingest at least a liquid diet and had a markedly decreased incidence of vomiting. During the follow-up of 2-116 weeks (mean, 25.5 weeks), stent migration occurred in two patients (10.0%) on one day after the procedure. All patients with stent migration were treated successfully by means of placing a second stent. Three patients showed a recurrence of the stricture due to tumor overgrowth; two of the patients were treated with coaxial placement of a second stent. Another patient refused additional management. Covered self-expandable metallic stent placement seems to be technically feasible and effective for palliative treatment of a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer

  8. Covered self-expandable metallic stent placement for a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woon Ha; Jung, Gyoo Sik; Kim, Kyu Jong; Lee, Sang Ho [Gospel Hospital, College of Medicine, Kosin University, Busan (Korea, Republic of); Ko, Ji Ho [Masan Samsung Medical Center, Sungkyunkwan University School of University, Masan (Korea, Republic of); Jeong, Kyung Soon [University of Ulsan Colleg of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2007-09-15

    To evaluate the technical feasibility and clinical effectiveness of stent placement for the treatment of a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer. Under fluoroscopic guidance, one or two covered stents were placed in 20 consecutive patients (age range, 44-75 years) with an anastomotic stricture due to a recurrent gastric malignancy. Before stent placement, all patients had severe nausea and recurrent vomiting after ingestion. Stent placement was technically successful for all patients, and no procedural complications occurred. After stent placement, 18 of 20 (90.0%) patients were able to ingest at least a liquid diet and had a markedly decreased incidence of vomiting. During the follow-up of 2-116 weeks (mean, 25.5 weeks), stent migration occurred in two patients (10.0%) on one day after the procedure. All patients with stent migration were treated successfully by means of placing a second stent. Three patients showed a recurrence of the stricture due to tumor overgrowth; two of the patients were treated with coaxial placement of a second stent. Another patient refused additional management. Covered self-expandable metallic stent placement seems to be technically feasible and effective for palliative treatment of a post-operative malignant anastomotic stricture secondary to recurrent gastric cancer.

  9. Implementing large scale fast track diagnostics in a comprehensive cancer center, pre- and post-measurement data.

    Science.gov (United States)

    van Harten, W H; Goedbloed, N; Boekhout, A H; Heintzbergen, S

    2018-02-07

    In general, patients with a cancer suspicion visit the hospital multiple times before diagnosis is completed. Using various "operations management" techniques a few fast track diagnostic services were implemented in the Netherlands Cancer Institute (NKI) in 2006. Growing patient numbers and increasing process complexity, led to diminished service levels. To decrease the amount of patient visits and to extend these services beyond the (obvious) breast cancer services, fast track diagnostics is now implemented for all 18 cancer types that present with a frequency of minimally one per week. The throughput time (first visit to diagnosis conversation) was measured before, and after implementation of fast track diagnostics. The process was redesigned closely involving the multidisciplinary teams. In an eclectic approach elements from lean management, theory of constraints and mathematical analysis were used to organize slots per tumor type for MRI, CT, PET and echography. A post measurement was performed after 3 and 6 months. In pre measurement access time was calculated to be 10 to 15 workdays, mean throughput time was 6.0 workdays. It proved possible to design the process of 18 tumors as a fast track, of which 7 as "one stop shop" (diagnosis completed in one visit). Involvement of clinical- and board leadership, massive communication efforts and commitment of physicians to reschedule their work proved decisive. After 3 and 6 months of implementation, the mean access time was 8.2 and 8.7 workdays respectively and mean throughput time was 3.4 and 3.3 workdays respectively. Throughput- and access time were considerably shortened after implementation of fast track diagnostics for 18 cancer types. The involvement of physicians in reorganizing their work and rapid responding to their needs during the implementation phase were a crucial success factor.

  10. Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.

    Science.gov (United States)

    Hertz, Daniel L; Speth, Kelly A; Kidwell, Kelley M; Gersch, Christina L; Desta, Zeruesenay; Storniolo, Anna Maria; Stearns, Vered; Skaar, Todd C; Hayes, Daniel F; Henry, N Lynn; Rae, James M

    2017-10-01

    The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer. Prior work suggests that anastrozole blood concentrations are associated with the magnitude of estrogen suppression. The objective of this study was to determine whether the magnitude of estrogen suppression, as determined by plasma estradiol (E2) concentrations, in EXE or LET treated patients is associated with plasma AI concentrations. Five hundred post-menopausal women with ER-positive breast cancer were enrolled in the prospective Exemestane and Letrozole Pharmacogenetic (ELPh) Study conducted by the COnsortium on BReast cancer phArmacogomics (COBRA) and randomly assigned to either drug. Estrogen concentrations were measured at baseline and after 3 months of AI treatment and drug concentrations were measured after 1 or 3 months. EXE or LET concentrations were compared with 3-month E2 concentration or the change from baseline to 3 months using several complementary statistical procedures. Four-hundred patients with on-treatment E2 and AI concentrations were evaluable (EXE n = 200, LET n = 200). Thirty (7.6%) patients (EXE n = 13, LET n = 17) had 3-month E2 concentrations above the lower limit of quantification (LLOQ) (median: 4.75; range: 1.42-63.8 pg/mL). EXE and LET concentrations were not associated with on-treatment E2 concentrations or changes in E2 concentrations from baseline (all p > 0.05). Steady-state plasma AI concentrations do not explain variability in E2 suppression in post-menopausal women receiving EXE or LET therapy, in contrast with prior evidence in anastrozole treated patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jun Won; Lee, Won Ae; Kim, You Me [Dankook University College of Medicine, Seoul (Korea, Republic of)

    2013-10-15

    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.

  12. Benefits and adverse effects of post-operative radiation therapy after radical cystectomy for patients with advanced bladder cancer

    International Nuclear Information System (INIS)

    Yabusaki, Noboru; Komatsu, Hideki; Tanabe, Nobuaki; Tago, Kiichiro; Ueno, Akira

    1995-01-01

    The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University Hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were PT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. During the follow-up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common. (author)

  13. 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

  14. The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

    Science.gov (United States)

    Lichtenberg, Shelly; Rahamimov, Ruth; Green, Hefziba; Fox, Benjamin D; Mor, Eytan; Gafter, Uzi; Chagnac, Avry; Rozen-Zvi, Benaya

    2017-07-01

    Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

  15. Disparities of time trends and birth cohort effects on invasive breast cancer incidence in Shanghai and Hong Kong pre- and post-menopausal women.

    Science.gov (United States)

    Wang, Feng; Tse, Lap Ah; Chan, Wing-Cheong; Kwok, Carol Chi-Hei; Leung, Siu-Lan; Wu, Cherry; Mang, Oscar Wai-Kong; Ngan, Roger Kai-Cheong; Li, Mengjie; Yu, Wai-Cho; Tsang, Koon-Ho; Law, Sze-Hong; Miao, Xiaoping; Wu, Chunxiao; Zheng, Ying; Wu, Fan; Yang, Xiaohong R; Yu, Ignatius Tak-Sun

    2017-05-23

    Breast cancer is the leading cause of cancer morbidity among Shanghai and Hong Kong women, which contributes to 20-25% of new female cancer incidents. This study aimed to describe the temporal trend of breast cancer and interpret the potential effects on the observed secular trends. Cancer incident data were obtained from the cancer registries. Age-standardized incidence rate was computed by the direct method using the World population of 2000. Average annual percentage change (AAPC) in incidence rate was estimated by the Joinpoint regression. Age, period and cohort effects were assessed by using a log-linear model with Poisson regression. During 1976-2009, an increasing trend of breast cancer incidence was observed, with an AAPC of 1.73 [95% confidence interval (CI): 1.54-1.92)] for women in Hong Kong and 2.83 (95% CI, 2.26-3.40) in Shanghai. Greater upward trends were revealed in Shanghai women aged 50 years old or above (AAPC = 3.09; 95% CI, 1.48-4.73). Using age at 50 years old as cut-point, strong birth cohort effects were shown in both pre- and post-menopausal women, though a more remarkable effect was suggested in Shanghai post-menopausal women. No evidence for a period effect was indicated. Incidence rate of breast cancer has been more speedy in Shanghai post-menopausal women than that of the Hong Kong women over the past 30 years. Decreased birth rate and increasing environmental exposures (e.g., light-at-night) over successive generations may have constituted major impacts on the birth cohort effects, especially for the post-menopausal breast cancer; further analytic studies are warranted.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  17. Provision of integrated psychosocial services for cancer survivors post-treatment

    Science.gov (United States)

    Recklitis, Christopher J; Syrjala, Karen L

    2018-01-01

    Meeting the psychosocial needs of patients with cancer has been recognised as a priority within oncology care for several decades. Many approaches that address these needs have been developed and described; however, until recently much of this work had focused on patients during treatment and end-of-life care. With continued improvement in therapies, the population of cancer survivors who can expect to live for 5 or more years after cancer diagnosis has increased dramatically, as have associated concerns about how to meet their medical, psychosocial, and health behaviour needs after treatment. Guidelines and models for general survivorship care routinely address psychosocial needs, and similar guidelines for psychosocial care of patients with cancer are being extended to address the needs of survivors. In this Series paper, we summarise the existing recommendations for the provision of routine psychosocial care to survivors, as well as the challenges present in providing this care. We make specific recommendations for the integration of psychosocial services into survivorship care. PMID:28049576

  18. Cancer survivors' views of work 3 years post diagnosis: a UK perspective.

    Science.gov (United States)

    Amir, Ziv; Neary, David; Luker, Karen

    2008-07-01

    The impact of cancer on people's working lives is an increasingly important concern but knowledge on this issue is very limited in the UK. Forty-one people of working age were purposively selected from the North Western Cancer Intelligence Service and interviewed by telephone to describe their experiences to returning to work following diagnosis and treatment. The data was subject to qualitative thematic analysis using NVIVO software. The results indicated the importance of returning to work from diagnosis and through treatment which was then followed by a re-assessment of work-life balance when people recovered from primary treatment and were back in employment. The principle motivations for returning to work were a quest for normality and financial pressures. One barrier to returning to work was the lack of medical advice from cancer specialists and general practitioners regarding the appropriate time to get back to work. A good relationship with their employer/manager was a major influence on returning to work and appeared to be related to duration of service rather than occupational status. These findings demonstrate the importance of paid work to people diagnosed with cancer and highlight the need to improve the support from medical professionals, especially oncology nurses.

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

    International Nuclear Information System (INIS)

    Ang, Kian K.; Garden, Adam S.

    1996-01-01

    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

  20. Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group

    International Nuclear Information System (INIS)

    Poortmans, Philip; Bossi, Alberto; Vandeputte, Katia; Bosset, Mathieu; Miralbell, Raymond; Maingon, Philippe; Boehmer, Dirk; Budiharto, Tom; Symon, Zvi; Bergh, Alfons C.M. van den; Scrase, Christopher; Poppel, Hendrik van; Bolla, Michel

    2007-01-01

    The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing post-operative radiotherapy for prostate cancer requires a standardisation of the target volume definition and delineation as well as standardisation of the clinical quality assurance procedures. Recommendations for this are presented on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group and in addition to the already published guidelines for radiotherapy as the primary treatment

  1. Obstructing Androgen Receptor Activation in Prostate Cancer Cells Through Post-translational Modification by NEDD8

    Science.gov (United States)

    2012-11-01

    FACS flow cytometer analysis . In addition, we will measure the steady state protein level of p53, p21, p27, and pRb. In the Jab1 silencing cell...affected by DHT treatment, and the endogenous AR level was not affected by Jab1 silencing. Interestingly, Western blot analysis of immunoprecipitated AR...Avantaggiati, and R. G. Pestell . 2003. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol

  2. Post-ERCP bacteremia caused by Alcaligenes xylosoxidans in a patient with pancreas cancer

    Directory of Open Access Journals (Sweden)

    Akcay Korhan

    2006-09-01

    Full Text Available Abstract Alcaligenes xylosoxidans is an aerobic, motile, oxidase and catalase positive, nonfermentative Gram negative bacillus. This bacterium has been isolated from intestine of humans and from various hospital or environmental water sources. A.xylosoxidans is both waterborne and results from the poor-hygienic conditions healthcare workers are in. In this case report, the bacteremia which appeared in a patient with pancreas cancer after ERCP was described.

  3. Immunological study of gastric cancer patients among a-bomb survivors, 2. Immunological status in post-operative patients

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Y; Tani, T; Yanagawa, E; Nakano, A; Nakanishi, K [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1981-01-01

    The changes of immunocompetence of post-operative gastric cancer patients who were exposed to a-bomb was investigated one month and three months after surgery, compared with patients who were not exposed to a-bomb, and the following results were obtained. 1. Skin reactions in both groups were almost the same. 2. Amounts of serum immunoglobulin (IgA, IgM, and IgG) in both groups varied only within a normal range. 3. Though juvenilization reaction of peripheral lymphocytes one month after surgery was lower than that before surgery in the stage I and II non-exposed group, it tended to recover 3 months after surgery. The stage I and II exposed group did not show a decrease in juvenilization reaction values one month after surgery. There was no statistically significant difference between both groups.

  4. Nutrition impact symptoms and associated outcomes in post-chemoradiotherapy head and neck cancer survivors: a systematic review.

    Science.gov (United States)

    Crowder, Sylvia L; Douglas, Katherine G; Yanina Pepino, M; Sarma, Kalika P; Arthur, Anna E

    2018-03-20

    It is estimated that more than 90% of head and neck cancer (HNC) survivors who underwent chemoradiotherapy experience one or more nutrition impact symptoms (NIS) in the months or years thereafter. Despite the high prevalence, there is limited research addressing long-term impact of NIS on outcomes such as nutrition and quality of life in HNC survivors treated with chemoradiotherapy. To conduct a systematic review of the literature pertaining to the presence of nutrition impact symptoms and their associated outcomes in post-chemoradiotherapy head and neck cancer survivors. A systematic review was conducted across three databases according to PRISMA guidelines and used to identify current literature regarding NIS in HNC survivors. A keyword search was conducted in PubMed, Scopus, and Web of Science from 2007 to 2017. Studies that met all of the following criteria were included in the review: (1) studies must include human subjects with a HNC diagnosis; (2) study participants must have received chemoradiotherapy; (3) study participants must have been post-treatment for a minimum of 3 months at the time of data collection; (4) full-text articles must have appeared in peer-reviewed journals; (5) papers must have been published in English; (6) studies must be quantitative in nature; (7) studies must have reported at least one NIS; and (8) studies must address at least one of the following outcomes: nutrition, functional status, or quality of life. Two independent reviewers assessed study quality using a predefined set of criteria. A systematic search yielded 1119 papers, of which 15 met the inclusion criteria. The study reviewed existing evidence of NIS in a variety of HNC survivors ranging from 3 months to greater than 10 years post-chemoradiotherapy treatment. Eight hundred forty-nine study participants were included in the review. Of the 15 studies, 10 were designed as prospective cohort studies, 4 were cross-sectional studies, and 1 was a retrospective cohort

  5. Prevalence and predictors of post-traumatic stress symptoms in adolescent and young adult cancer survivors: a 1-year follow-up study.

    Science.gov (United States)

    Kwak, Minyoung; Zebrack, Brad J; Meeske, Kathleen A; Embry, Leanne; Aguilar, Christine; Block, Rebecca; Hayes-Lattin, Brandon; Li, Yun; Butler, Melissa; Cole, Steven

    2013-08-01

    Post-traumatic stress symptoms (PTSS) have been identified as a meaningful indicator of distress in cancer survivors. Distinct from young adult survivors of childhood cancer, young people diagnosed with cancer as adolescents and young adults (AYAs) face unique psychosocial issues; however, there is little published research of PTSS in the AYA population. This study examines prevalence and predictors of PTSS among AYAs with cancer. As part of a longitudinal study of AYAs with cancer, 151 patients aged 15-39 years completed mailed surveys at 6 and 12 months post-diagnosis. Severity of PTSS was estimated at 6 and 12 months post-diagnosis. Multiple regression analyses were conducted to investigate the predictive effects of socio-demographic and clinical characteristics on changes in PTSS over time. At 6 and 12 months, respectively, 39% and 44% of participants reported moderate to severe levels of PTSS; 29% had PTSS levels suggestive of post-traumatic stress disorder. No significant differences in severity of PTSS between 6 and 12 months were observed. Regression analyses suggested that a greater number of side effects were associated with higher levels of PTSS at 6 months. Currently receiving treatment, having surgical treatment, diagnosis of a cancer type with a 90-100% survival rate, remaining unemployed/not in school, and greater PTSS at 6 months were associated with higher levels of PTSS at 12 months. Post-traumatic stress symptoms were observed as early as 6 months following diagnosis and remained stable at 12-month follow-up. The development of early interventions for reducing distress among AYA patients in treatment is recommended. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Influence of smoking status on treatment outcomes after post-operative radiation therapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Nguyen, Sonia K.A.; Masson-Cote, Laurence; Fortin, Andre; Dagnault, Anne

    2010-01-01

    Background and purpose: The role of post-operative radiotherapy in patients with resected non-small-cell lung cancer (NSCLC) is unclear. Modifiable factors, like smoking, may help guide therapy. We retrospectively evaluated the impact of smoking on control in patients undergoing post-operative radiation therapy (PORT) for NSCLC. Materials and methods: Between 1995 and 2007, 152 patients who underwent surgery for NSCLC were analyzed (median follow-up 26 months). Non-smokers were defined as patients who never smoked or who had stopped smoking at the time of initial consultation. Sixty seven percent were non-smokers; 5% never smoked, 40% of the non-smokers had ceased smoking for a year or less, while 55% had stopped for more than a year. Results: On univariate analysis, smokers had worse 5-year local control than non-smokers (70% versus 90%, p = 0.001) and locoregional control (52% versus 77%, p = 0.002). The 5 -year survival rate was 21% for smokers and 31% for non-smokers (p = 0.2). On multivariate analysis, smokers maintained a detrimental effect on locoregional control (HR 3.6, p = 0.0006). Conclusions: Smokers at initial consultation have poorer local and locoregional control after PORT than non-smokers. In patients being considered for PORT for NSCLC, quitting smoking before treatment confers additional treatment advantage.

  7. 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.

  8. Patient perspectives: Tijuana cancer clinics in the post-NAFTA era.

    Science.gov (United States)

    Moss, Ralph W

    2005-03-01

    This article contains observations and historical considerations on cancer and complementary and alternative medicine (CAM) in the Tijuana, Mexico, area. There are approximately 2 dozen such clinics in Tijuana, some of which have been treating international cancer patients since 1963. Among the first clinics to be established were the Bio-Medical Center (Hoxsey therapy), Oasis of Hope (a Laetrile-oriented clinic), and a series of clinics affiliated with the Gerson diet therapy. These original clinics were established mainly by American citizens in response to increased regulation of nonstandard therapies in the United States, particularly after passage of the Kefauver-Harris Amendments to the Food, Drug and Cosmetics Act in 1962. In the 1970s, the Tijuana clinics proliferated with the upsurge of interest in Laetrile (amygdalin). By 1978, 70,000 US cancer patients had taken Laetrile for cancer treatment, and many of those had gone to Tijuana to receive it. The popularity of the Tijuana clinics peaked in the mid-1980s. Although many new clinics opened after then, a dozen have folded in the past 10 years alone. The turning point for the clinics came with passage of the North American Free Trade Agreement (NAFTA), which facilitated greater cooperation among the antifraud authorities of Canada, the United States, and Mexico. In 1994, the tripartite members of NAFTA formed the Mexico-United States-Canada Health Fraud Work Group, or MUCH, whose brief is to strengthen the 3 countries' ability to prevent cross-border health fraud. Under the auspices of MUCH and its members, regulatory crackdowns began in earnest early in 2001. The clinics were also badly affected by the general downturn in travel after 9/11. If these trends continue, many Tijuana clinics are unlikely to survive. Some suggestions are made for how the Tijuana clinics could be reorganized and reformed to minimize the likelihood of governmental actions and to maximize public support. Such reforms center on 5

  9. ADDITIONAL VALUE OF POST-THERAPY 131 I SPECT/CT IN PATIENTS WITH DIFFERENTIATED THYROID CANCER

    Directory of Open Access Journals (Sweden)

    Satyawati Deswal

    2017-03-01

    Full Text Available BACKGROUND Generally, it is seen that SPECT/CT images are more useful than the planar images. We compared post-therapy 131 I imaging findings on planar and SPECT/CT scans to assess the clinical utility of SPECT/CT in management of patients with differentiated thyroid cancer. MATERIALS AND METHODS Post-therapy imaging was performed at 4-7 (when 5mR/hrs. exposure rate were observed by the survey meter days after 131 I administration and all patients underwent whole-body scintigraphy and SPECT/CT scanning on the same day. A generalised McNemar 1 was used to determine to establish the agreement between planar whole-body imaging and SPECT/CT for the assignment of benign, equivocal and malignant findings. RESULTS In 44 patients, 32 of the 44 patients underwent postsurgical 131 I ablation of residual thyroid tissue and 12 of 44 patients, 2 patients were treated twice. Hence, a total of 46 scans were analysed. SPECT/CT helped to localise focal iodine uptake and characterise it as either normal or abnormal thereby reducing the need for additional imaging studies. In post-thyroidectomy patients, SPECT/CT findings affected the ATA risk classification with implications for management by changing the interval for clinical followup and the need for additional imaging and laboratory tests. Our study found an 11% change in nodal status in the postsurgical group. Change in patient management was observed in 18%. CONCLUSION SPECT/CT enabled more accurate characterisation of focal iodine accumulation in patients.

  10. Socioeconomic Factors Associated with Post-Mastectomy Immediate Reconstruction in a Contemporary Cohort of Breast Cancer Survivors.

    Science.gov (United States)

    Schumacher, Jessica R; Taylor, Lauren J; Tucholka, Jennifer L; Poore, Samuel; Eggen, Amanda; Steiman, Jennifer; Wilke, Lee G; Greenberg, Caprice C; Neuman, Heather B

    2017-10-01

    Post-mastectomy reconstruction is a critical component of high-quality breast cancer care. Prior studies demonstrate socioeconomic disparity in receipt of reconstruction. Our objective was to evaluate trends in receipt of immediate reconstruction and examine socioeconomic factors associated with reconstruction in a contemporary cohort. Using the National Cancer Database, we identified women rates (2004-2013) for the overall cohort and stratified by socioeconomic factors were examined using Join-point regression analysis, and annual percentage change (APC) was calculated. We then restricted our sample to a contemporary cohort (2010-2013, n = 145,577). Multivariable logistic regression identified socioeconomic factors associated with immediate reconstruction. Average adjusted predicted probabilities of receiving reconstruction were calculated. Immediate reconstruction rates increased from 27 to 48%. Although absolute rates of reconstruction for each stratification group increased, similar APCs across strata led to persistent gaps in receipt of reconstruction. On multivariable logistic regression using our contemporary cohort, race, income, education, and insurance type were all strongly associated with immediate reconstruction. Patients with the lowest predicted probability of receiving reconstruction were patients with Medicaid who lived in areas with the lowest rates of high-school graduation (Black 42.4% [95% CI 40.5-44.3], White 45.7% [95% CI 43.9-47.4]). Although reconstruction rates have increased dramatically over the past decade, lower rates persist for disadvantaged patients. Understanding how socioeconomic factors influence receipt of reconstruction, and identifying modifiable factors, are critical next steps towards identifying interventions to reduce disparities in breast cancer surgical care.

  11. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

    Science.gov (United States)

    Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

    2017-06-01

    Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

  12. Evidence supporting contemporary post-operative radiation therapy (PORT) using linear accelerators in N2 lung cancer.

    Science.gov (United States)

    Patel, Suchit H; Ma, Yan; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, K S C; Parashar, Bhupesh

    2014-05-01

    Post-operative radiotherapy (PORT) treatment for lung cancer declined since a meta-analysis failed to show benefit in patients with N2 disease. Because several included studies employed outmoded radiation planning and delivery techniques, we sought to determine whether PORT with modern technology benefits patients with N2 disease. We conducted searches of the published literature. For inclusion, studies must have included patients with stage III-N2 lung cancer treated with PORT using only linear accelerators, used a control group that did not receive PORT, and reported outcome data for overall survival (OS). Prospective and retrospective analyses were included. Exclusion criteria were the use of cobalt devices or orthovoltage radiation. Data were evaluated with random-effects models. Three prospective and eight retrospective studies were included. The PORT and no-PORT groups included 1368 and 1360 patients, respectively. The PORT group had significantly improved OS over the no-PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data was available was also improved in the PORT group (HR = 0.51, CI 0.41-0.65, P PORT was associated with significantly lower risk of death and locoregional recurrence in patients with N2 lung cancer. Our study was limited by lack of access to individual patient data, which would have enabled more detailed analyses. Regardless, data thus far suggest PORT may be associated with a survival benefit. Given a lack of large-scale prospective data, clinical trials evaluating PORT with modern technology are warranted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Hashmi, Salman; Zolfaghari, Ladan; 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 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

  14. [Cost-effectiveness analysis of adjuvant anastrozol in post-menopausal women with breast cancer].

    Science.gov (United States)

    Sasse, Andre Deeke; Sasse, Emma Chen

    2009-01-01

    Carry out an economic analysis of the incorporation of anastrozole as adjuvant hormone therapy in postmenopausal women with breast cancer in a Brazilian setting. The cost-effectiveness estimate comparing anastrozole to tamoxifen was made from the perspectives of the patient, private health insurance, and government. A Markov model was designed based on data from ATAC trial after 100 months follow-up in a hypothetical cohort of 1000 postmenopausal women in Brazil, using outcomes projections for a 25-year period. Resource utilization and associated costs were obtained from preselected sources and specialists' opinions. Treatment costs varied according to the perspective used. The incremental benefit was inserted in the model to obtain the cost of quality-adjusted life-year gained (QALY). Benefit extrapolations for a 25-year time line showed an estimate of 0.29 QALY gained with anastrozole compared to tamoxifen. The cost-effectiveness ratio per QALY gained depended on which perspective was used. There was an increment of R$ 32.403,00/QALY in the public health system/government, R$ 32.230,00/QALY for private health system, and R$ 55.270,00/QALY for patients. The benefit from adjuvant anastrozole in postmenopausal patients with breast cancer is associated to major differences in cost-effectiveness ratio and varies with the different perspectives. According to current WHO parameters, the increment is considered acceptable under public and private health system perspectives, but not from that of the patient.

  15. 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.

  16. Fertility information needs and concerns post-treatment contribute to lowered quality of life among young adult female cancer survivors.

    Science.gov (United States)

    Benedict, Catherine; Thom, Bridgette; Friedman, Danielle N; Pottenger, Elaine; Raghunathan, Nirupa; Kelvin, Joanne F

    2018-07-01

    Cancer treatment may lead to premature menopause and infertility. Young adult female cancer survivors (YAFCS) are often concerned about their fertility and future family-building options, but research is limited on how concerns may affect more general quality of life (QOL) domains. This study examined how fertility factors relate to QOL among YAFCS who received gonadotoxic therapy. A national sample of YAFCS completed an online, anonymous survey. The survey included investigator-designed questions about perceived fertility information needs (five items; Cronbach's α = .83) and general QOL (four items; α = .89), the Reproductive Concerns after Cancer Scale (RCACS) and Decisional Conflict Scale (DCS). Analyses included Pearson's correlation, t tests, and stepwise regression. Participants (N = 314) were an average of 30 years old (SD = 4.1) and 5 years (SD = 5.4) post-treatment; 31% reported being infertile and 19% had undergone fertility preservation (FP). Overall, QOL was relatively high (M = 7.3, SD = 1.9, range 0-10) and did not vary by fertility status (t[272] = .743, p = .46), prior FP (t[273] = .53, p = .55) or sociodemographic/clinical factors (p's > .05) except socioeconomic indicators (p's < .05).In separate models, greater unmet fertility information needs (β = - .19, p = .004) and, among fertile women, greater reproductive concerns (β = - .26, p = .001) related to lower QOL. Among fertile women without prior FP, greater decisional distress about future FP related to lower QOL (β = - .19, p = .03). These preliminary findings suggest that unaddressed fertility information needs, concerns, and decision distress may affect general QOL among post-treatment YAFCS who hope to have children in the future. Future work should identify ways to optimally incorporate fertility counseling and support resources into survivorship care programs, including referrals to reproductive

  17. Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery.

    Science.gov (United States)

    Breen, Kieran J; O'Neill, Amanda; Murphy, Lisa; Fan, Yue; Boyce, Susie; Fitzgerald, Noel; Dorris, Emma; Brady, Lauren; Finn, Stephen P; Hayes, Brian D; Treacy, Ann; Barrett, Ciara; Aziz, Mardiana Abdul; Kay, Elaine W; Fitzpatrick, John M; Watson, R William G

    2017-09-01

    Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. INSR (P IGF-1R (P IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR. © 2017 Wiley Periodicals, Inc.

  18. The flare in alkaline phosphatase activity post-orchidectomy predicts which patient may benefit from early chemotherapy in metastatic prostate cancer

    NARCIS (Netherlands)

    Pelger, Rob C. M.; Lycklama A Nijeholt, Guus A. B.; Zwinderman, Aielko H.; Hamdy, Neveen A. T.

    2002-01-01

    BACKGROUND: A flare in serum alkaline phosphatase (ALP) activity post-orchidectomy has been shown to be of negative prognostic value for progression-free survival (PFS) in patients with prostate cancer. The aim of this study was to investigate whether a flare in ALP may help identify patients in

  19. Reducing recurrence in non-muscle-invasive bladder cancer using photodynamic diagnosis and immediate post-transurethral resection of the bladder chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg; Nielsen, Tommy Kjærgaard; Zieger, Karsten Egbert Arnold

    2015-01-01

    Abstract Objective. The aim of this study was to evaluate the effect of fluorescence cystoscopy and immediate post-transurethral resection of the bladder (TURB) chemoprophylaxis on the risk of recurrence of non-muscle-invasive bladder cancer (NMIBC) under routine clinical conditions. Materials...

  20. A systematic literature review exploring the prevalence of post-traumatic stress disorder and the role played by stress and traumatic stress in breast cancer diagnosis and trajectory.

    Science.gov (United States)

    Arnaboldi, Paola; Riva, Silvia; Crico, Chiara; Pravettoni, Gabriella

    2017-01-01

    Stress has been extensively studied as a psychosomatic factor associated with breast cancer. This study aims to review the prevalence of post-traumatic stress disorder (PTSD), its associated risk factors, the role of predicting factors for its early diagnosis/prevention, the implications for co-treatment, and the potential links by which stress could impact cancer risk, by closely examining the literature on breast cancer survivors. The authors systematically reviewed studies published from 2002 to 2016 pertaining to PTSD, breast cancer and PTSD, and breast cancer and stress. The prevalence of PTSD varies between 0% and 32.3% mainly as regards the disease phase, the stage of disease, and the instruments adopted to detect prevalence. Higher percentages were observed when the Clinician Administered PTSD Scale was administered. In regard to PTSD-associated risk factors, no consensus has been reached to date; younger age, geographic provenance with higher prevalence in the Middle East, and the presence of previous cancer diagnosis in the family or relational background emerged as the only variables that were unanimously found to be associated with higher PTSD prevalence. Type C personality can be considered a risk factor, together with low social support. In light of the impact of PTSD on cognitive, social, work-related, and physical functioning, co-treatment of cancer and PTSD is warranted and a multidisciplinary perspective including specific training for health care professionals in communication and relational issues with PTSD patients is mandatory. However, even though a significant correlation was found between stressful life events and breast cancer incidence, an unequivocal implication of distress in breast cancer is hard to demonstrate. For the future, overcoming the methodological heterogeneity represents one main focus. Efficacy studies could help when evaluating the effect of co-treating breast cancer and post-traumatic stress symptoms, even if all the

  1. Sleep, quality of life and depression in women in breast cancer post-treatment

    OpenAIRE

    Rafihi-Ferreira, Renatha El; Pires, Maria Laura Nogueira; Soares, Maria Rita Zoéga

    2012-01-01

    Este trabalho investigou a qualidade de sono de mulheres com câncer de mama e suas relações com qualidade de vida e depressão. Cinqüenta mulheres com câncer de mama (grupo clínico) e cinqüenta controles responderam um questionário médico-demográfico e ao instrumento Pittsburgh Sleep Quality Index. O grupo clínico também respondeu aos instrumentos Quality of Life Cancer-Survivor e Brief Zung Self-Rating Depression Scale. Verificou-se que mulheres com câncer tinham significativamente mais queix...

  2. 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.

  3. Decision aid use during post-biopsy consultations for localized prostate cancer.

    Science.gov (United States)

    Holmes-Rovner, Margaret; Srikanth, Akshay; Henry, Stephen G; Langford, Aisha; Rovner, David R; Fagerlin, Angela

    2018-02-01

    Decision Aids (DAs) effectively translate medical evidence for patients but are not routinely used in clinical practice. Little is known about how DAs are used during patient-clinician encounters. To characterize the content and communicative function of high-quality DAs during diagnostic clinic visits for prostate cancer. 252 men newly diagnosed with localized prostate cancer who had received a DA, 45 treating physicians at 4 US Veterans Administration urology clinics. Qualitative analysis of transcribed audio recordings was used to inductively develop categories capturing content and function of all direct references to DAs (booklet talk). The presence or absence of any booklet talk per transcript was also calculated. Booklet talk occurred in 55% of transcripts. Content focused on surgical procedures (36%); treatment choice (22%); and clarifying risk classification (17%). The most common function of booklet talk was patient corroboration of physicians' explanations (42%), followed by either physician or patient acknowledgement that the patient had the booklet. Codes reflected the absence of DA use for shared decision-making. In regression analysis, predictors of booklet talk were fewer years of patient education (P = .027) and more time in the encounter (P = .027). Patient race, DA type, time reading the DA, physician informing quality and physician age did not predict booklet talk. Results show that good decision aids, systematically provided to patients, appeared to function not to open up deliberations about how to balance benefits and harms of competing treatments, but rather to allow patients to ask narrow technical questions about recommended treatments. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  4. SU-F-T-87: Comparison of Advanced Radiotherapy Techniques for Post- Mastectomy Breast Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Heins, D; Zhang, R [Louisiana State University, Baton Rouge, LA (United States); Hogstrom, K; Sanders, M [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States)

    2016-06-15

    Purpose: To determine if bolus electron conformal therapy (Bolus-ECT) combined with intensity modulated x-ray therapy (IMXT) and flattening filter free volumetric modulated arc therapy (FFF-VMAT (6x and 10x)) can maintain equal or better dose coverage than standard volumetric modulated arc therapy (Std-VMAT) while reducing doses to organs at risk (OARs). Methods: Bolus-ECT with IMXT, FFF-VMAT, and Std-VMAT treatment plans were produced for ten post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic. The treatment plans were created on commercially available treatment planning system (TPS) and all completed treatment plans were reviewed and approved by a radiation oncologist. The plans were evaluated based on planning target volume (PTV) coverage, tumor control probability (TCP), dose homogeneity index (DHI), conformity index (CI), and dose to organs at risk (OAR). Results: All techniques produced clinically acceptable PMRT plans. Overall, Bolus-ECT with IMXT exhibited higher maximum dose compared to all VMAT techniques. Bolus-ECT with IMXT and FFF-VMAT10x had slightly improved TCP over FFF-VMAT6x and Std-VMAT. However, all VMAT techniques showed improved CI and DHI over Bolus-ECT with IMXT. All techniques showed very similar mean lung dose. Bolus-ECT with IMXT exhibited a reduced mean heart dose over Std-VMAT. Both FFF-VMAT techniques had higher mean heart dose compared to Std-VMAT. In addition, Bolus-ECT with IMXT was able to reduce mean dose to the contralateral breast compared to Std-VMAT and both FFF-VMAT techniques had comparable but slightly reduced dose compared to Std-VMAT. Conclusion: This work has shown that Bolus-ECT with IMXT produces clinically acceptable plans while reducing OAR doses. Both FFF-VMAT techniques are comparable to Std-VMAT with slight improvements. Even though all VMAT techniques produce more homogenous and conformal dose distributions, Bolus-ECT with IMXT is a viable option for treating post-mastectomy patients

  5. Intermittent hormonal therapy in the treatment of post-irradiation residual/recurrent prostate cancer

    International Nuclear Information System (INIS)

    Williams, Aaron O; Kocherill, Paul G; Wallace, Michelle; Forman, Jeffrey D

    1996-01-01

    Purpose: To evaluate the efficacy and toxicity of intermittent hormonal therapy in the treatment of residual/recurrent prostate cancer. Materials and Methods: Seventeen patients with biochemical evidence of residual/recurrent prostate cancer were initially treated with radiation therapy (RT)(13), neo-adjuvant hormonal therapy and RT (3), or RT following prostatectomy (1). The mean follow-up time was 19.4 months from the initiation of hormonal therapy. Hormonal therapy consisted of an LH-RH agonist alone (7), an anti-androgen alone (1) or a combination of both (9). Hormonal therapy was continued until the prostatic specific antigen (PSA) level became undetectable. IHT was reinstituted when the PSA reached a pre-determined level, usually greater than or equal to 10ng/ml. Results: The mean time from completion of primary treatment to the initiation of hormonal therapy was 32.5 months. The mean PSA at the start of the first cycle of hormonal therapy was 43.9ng/ml, the second cycle, 11.9ng/ml and the third cycle, 24ng/ml. The mean PSA levels at the end of the first and second cycle of hormonal therapy were .48 and .42ng/ml, respectively. No patient has yet completed the third cycle of hormonal therapy. The average duration of hormonal therapy was 10 months for the first cycle and 4 months for the second cycle. The mean intermittent time off hormones were 9.3 months between cycles 1 and 2, and 10 months between cycles 2 and 3. No patient has yet become refractory to hormonal therapy. Currently all patients are alive. All patients experienced hot flashes and decreased libido at varying degrees during treatment. Thirty-five percent experienced gynecomastia. During the intervals between hormonal therapy, most patients reported a decrease in hot flashes. Conclusion: This analysis supplies preliminary evidence that intermittent hormonal therapy is a viable option in patients with biochemical evidence of disease following initial therapy. It is associated with less treatment

  6. Dental consultation in patients planned for/undergoing/post radiation therapy for head and neck cancers: a questionnaire-based survey.

    Science.gov (United States)

    Mainali, Apeksha; Sumanth, K N; Ongole, Ravikiran; Denny, Ceena

    2011-01-01

    Mouth and pharyngeal cancers account for approximately 6% of cancers worldwide. Radiotherapy is one of the means of treatment of head and neck cancer. Consultation with a dental team experienced in caring for patients undergoing treatment for head and neck cancer will improve the quality of life of such patients. To evaluate the attitude of oncologists toward dental consultation to patients planning for/prior to/undergoing/post radiation therapy for head and neck cancers and to evaluate the number of radiation oncologists who encounter oral complaints and consider worth referring to a dentist. A questionnaire-based study was carried out following mailing of covering letter and self-administered questionnaire comprising 11 items, to 25 radiation oncology centers selected in India based on convenient sampling. Out of the 25 centers, we received response from 20 centers with 60 completely filled questionnaires. Five centers did not respond for further correspondences. The study indicated a need for awareness and education among radiation oncologists regarding dental consultation in patients planned/undergoing /post radiation therapy for head and neck cancer.

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

    International Nuclear Information System (INIS)

    Urban, Damien; Gluck, Iris; Pfeffer, M. Raphael; Symon, Zvi; Lawrence, Yaacov R.

    2013-01-01

    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

  8. A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paul Savage

    2017-10-01

    Full Text Available Summary: Therapies targeting epidermal growth factor receptor (EGFR have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC patient-derived xenografts (PDXs, we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster. Sorted EGFRhi subpopulations exhibited enhanced stem-like features, including ALDH activity, sphere-forming efficiency, and tumorigenic and metastatic potential. EGFRhi cells gave rise to EGFRhi and EGFRlo cells in primary and metastatic tumors, demonstrating an EGFR-dependent expansion and hierarchical state transition. Similar tumorigenic EGFRhi subpopulations were identified in independent PDXs, where heterogeneous EGFR expression correlated with gefitinib sensitivity. This provides new understanding for an EGFR-dependent hierarchy in TNBC and for patient stratification for therapeutic intervention. : Savage et al. demonstrate that sensitivity to EGFR inhibitor, gefitinib, in triple-negative breast cancer is paradoxically associated with EGFR heterogeneity. Using single-cell RNA sequencing in conjunction with functional assays, they identify TNBC tumors in which EGFR expression identifies cells with tumor-initiating capacity whose proliferative expansion is sensitive to EGFR inhibition. Keywords: breast cancer, tumor heterogeneity, patient-derived xenograft, single-cell RNA sequencing, EGFR inhibition, therapeutic response, tumor-initiating cell, cell hierarchy, BRCA1 mutation

  9. Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

    2015-09-01

    Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

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

    International Nuclear Information System (INIS)

    Zhang, Jian; Gong, Youling; Peng, Feng; Li, Na; Liu, Yongmei; Xu, Yong; Zhou, Lin; Wang, Jin; Zhu, Jiang; Huang, Meijuan

    2012-01-01

    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

  11. Breast Cancer Patients' Preferences for Adjuvant Radiotherapy Post Lumpectomy: Whole Breast Irradiation vs. Partial Breast Irradiation-Single Institutional Study.

    Science.gov (United States)

    Bonin, Katija; McGuffin, Merrylee; Presutti, Roseanna; Harth, Tamara; Mesci, Aruz; Feldman-Stewart, Deb; Chow, Edward; Di Prospero, Lisa; Vesprini, Danny; Rakovitch, Eileen; Lee, Justin; Paszat, Lawrence; Doherty, Mary; Soliman, Hany; Ackerman, Ida; Cao, Xingshan; Kiss, Alex; Szumacher, Ewa

    2018-02-01

    This study was conducted to elucidate patients with early breast cancer preference for standard whole breast irradiation (WBI) or partial breast irradiation (PBI) following lumpectomy, as well as identify important factors for patients when making their treatment decisions. Based on relevant literature and ASTRO consensus statement guidelines, an educational tool and questionnaire were developed. Consenting, eligible women reviewed the educational tool and completed the trade-off questionnaire. Descriptive statistics were calculated, as well as chi-squares and a logistic regression model. Of the 90 patients who completed the study, 62 % preferred WBI, 30 % preferred PBI, 4 % required more information, and 3 % had no preferences. Of the patients who chose WBI, 58 % preferred hypofractionated RT, whereas 25 % preferred the conventional RT regimen. The majority of patients rated recurrence rate [WBI = 55/55 (100 %), PBI = 26/26 (100 %)] and survival [WBI = 54/55 (98 %), PBI = 26/26 (100 %)] as important factors contributing to their choice of treatment preference. Financial factors [WBI = 21/55 (38 %), PBI = 14/26 (53 %)] and convenience [WBI = 36/54 (67 %), PBI = 18/26 (69 %)] were rated as important less frequently. Significantly, more patients who preferred WBI also rated standard method of treatment as important when compared to patients who preferred PBI [WBI = 52/54 (96 %), PBI = 16/26 (61 %), χ 2  = 16.63, p = 0.001]. The majority of patients with early breast cancer who were surveyed for this study preferred WBI as an adjuvant treatment post lumpectomy, yet there was a sizeable minority who preferred PBI. This was associated with the importance patients place on standard treatment. These results will help medical professionals treat patients according to patient values.

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

    Directory of Open Access Journals (Sweden)

    Zhang Jian

    2012-06-01

    Full Text Available Abstract Purpose To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. Methods 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. Results 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  Conclusions 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.

  13. A systematic literature review exploring the prevalence of post-traumatic stress disorder and the role played by stress and traumatic stress in breast cancer diagnosis and trajectory

    Directory of Open Access Journals (Sweden)

    Arnaboldi P

    2017-07-01

    Full Text Available Paola Arnaboldi,1 Silvia Riva,2 Chiara Crico,2 Gabriella Pravettoni1 1Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology, 2Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy Abstract: Stress has been extensively studied as a psychosomatic factor associated with breast cancer. This study aims to review the prevalence of post-traumatic stress disorder (PTSD, its associated risk factors, the role of predicting factors for its early diagnosis/prevention, the implications for co-treatment, and the potential links by which stress could impact cancer risk, by closely examining the literature on breast cancer survivors. The authors systematically reviewed studies published from 2002 to 2016 pertaining to PTSD, breast cancer and PTSD, and breast cancer and stress. The prevalence of PTSD varies between 0% and 32.3% mainly as regards the disease phase, the stage of disease, and the instruments adopted to detect prevalence. Higher percentages were observed when the Clinician Administered PTSD Scale was administered. In regard to PTSD-associated risk factors, no consensus has been reached to date; younger age, geographic provenance with higher prevalence in the Middle East, and the presence of previous cancer diagnosis in the family or relational background emerged as the only variables that were unanimously found to be associated with higher PTSD prevalence. Type C personality can be considered a risk factor, together with low social support. In light of the impact of PTSD on cognitive, social, work-related, and physical functioning, co-treatment of cancer and PTSD is warranted and a multidisciplinary perspective including specific training for health care professionals in communication and relational issues with PTSD patients is mandatory. However, even though a significant correlation was found between stressful life events and breast cancer incidence, an unequivocal implication of

  14. Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement

    International Nuclear Information System (INIS)

    Racadot, Severine; Mercier, Mariette; Dussart, Sophie; Dessard-Diana, Bernadette; Bensadoun, Rene-Jean; Martin, Michel; Malaurie, Emmanuelle; Favrel, Veronique; Housset, Martin; Durdux, Catherine; Journel, Catherine; Calais, Gilles; Huet, Jocelyne; Pillet, Gerard; Hennequin, Christophe; Haddad, Elias; Diana, Christian; Blaska-Jaulerry, Brigitte; Henry-Amar, Michel; Gehanno, Pierre

    2008-01-01

    Background and purpose: Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. Materials and methods: The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72 Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50 mg/m 2 administered by IV infusion twice weekly). Results: Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p = 0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p = 0.81). Conclusions: Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers

  15. A screening algorithm for early detection of major depressive disorder in head and neck cancer patients post-treatment: Longitudinal study.

    Science.gov (United States)

    Henry, Melissa; Rosberger, Zeev; Ianovski, Lola E; Hier, Michael; Zeitouni, Anthony; Kost, Karen; Mlynarek, Alex; Black, Martin; MacDonald, Christina; Richardson, Keith; Zhang, Xun; Fuhrmann, Fabienne; Chartier, Gabrielle; Frenkiel, Saul

    2018-03-13

    The primary purpose of this study was to identify predictors of Major Depressive Disorder in head and neck cancer (HNC) patients in the immediate post-treatment period (ie, at 3 months post-diagnosis), with a focus on previously unexamined historical and contextual factors. Prospective longitudinal study of 223 consecutive adults (72% participation) newly diagnosed with a first occurrence of primary HNC, including validated psychometric measures, Structured Clinical Interviews for DSM Disorders, and medical chart reviews. The 3-month period prevalence of Major Depressive Disorder was 20.4%; with point prevalences of 6.8% upon HNC diagnosis, 14.2% at 3 months, and 22.6% lifetime. Patients most susceptible to developing Major Depressive Disorder in the immediate post-treatment period: were diagnosed with advanced-stage cancer rather than early-stage cancer (O.R. = 4.94, P = 0.04), received surgery only (O.R. = 8.73, P = 0.04), presented a lifetime history of Anxiety Disorder on SCID-I (O.R. = 6.62; P = 0.01), and indicated higher pre-treatment levels of anxiety on the HADS (O.R. = 0.45, P = 0.05). Our results outline the predominant role of anxiety upon diagnosis as a precursor to post-treatment Major Depressive Disorder, suggesting the need for identification and prophylactic treatment of anxiety upon diagnosis in head and neck cancer patients. Further investigation into pathways by which pre-treatment anxiety predisposes to post-treatment Major Depressive Disorder in this population is warranted. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Population Level Effects of a Mass Media Alcohol and Breast Cancer Campaign: A Cross-Sectional Pre-Intervention and Post-Intervention Evaluation.

    Science.gov (United States)

    Martin, Neil; Buykx, Penny; Shevills, Colin; Sullivan, Claire; Clark, Lynsey; Newbury-Birch, Dorothy

    2018-01-01

    To examine the relationship between a TV-led breast cancer mass-media campaign in the North East of England (conducted in two waves: Jul/2015 and Nov/2015), awareness of the link between alcohol and cancer, intention to reduce alcohol consumption and support for alcohol related policies. Three cross-sectional surveys were conducted; one over the 2 weeks pre-campaign (n = 572); one immediately following campaign wave 1 (n = 576); and another immediately following campaign wave 2 (n = 552). Survey questions assessed; campaign exposure; awareness of the links between alcohol and related cancers; intention to change alcohol consumption; and support for alcohol related policies. The proportion of respondents indicating awareness of alcohol as a cancer risk factor was larger post-campaign compared to pre-campaign. The largest increase was seen for breast cancer with 45% aware of the links post-campaign wave 2 compared to 33% pre-campaign. The proportion of respondents indicating 'strong support' of the seven alcohol related policies significantly increased between surveys. The proportion of respondents both aware of alcohol as a cancer risk factor and supportive of the seven alcohol related policies significantly increased between surveys. There was no significant change in self-reported intention to reduce alcohol consumption amongst increasing/higher risk drinkers. These findings indicate that a mass-media campaign raising awareness of the links between alcohol and breast cancer is associated with increased awareness and alcohol related policy support at a population level. However, there was no association found with a change in short-term drinking intentions. A mass-media campaign raising awareness of the links between alcohol and breast cancer is associated with increased awareness and alcohol policy support at a population level but does not appear to be associated with a change in short term drinking intentions. © The Author 2017. Medical Council on Alcohol and

  17. Work-specific cognitive symptoms and the role of work characteristics, fatigue and depressive symptoms in cancer patients during 18 months post return to work.

    Science.gov (United States)

    Dorland, H F; Abma, F I; Roelen, C A M; Stewart, R; Amick, B C; Bültmann, U; Ranchor, A V

    2018-06-19

    Cancer patients can experience work-specific cognitive symptoms post return to work (RTW). The study aims to: 1) describe the course of work-specific cognitive symptoms in the first 18 months post RTW, and 2) examine the associations of work characteristics, fatigue and depressive symptoms with work-specific cognitive symptoms over time. This study used data from the 18-months longitudinal "Work Life after Cancer" cohort. The Cognitive Symptom Checklist-Work, Dutch Version (CSC-W DV) was used to measure work-specific cognitive symptoms. Linear mixed models were performed to examine the course of work-specific cognitive symptoms during 18 months follow-up; linear regression analyses with generalised estimating equations (GEE) were used to examine associations over time. Working cancer patients diagnosed with different cancer types were included (n=378). Work-specific cognitive symptoms were stable over 18 months. At baseline, cancer patients reported more working memory symptoms (M=31.9, CI=23.1, 26.4) compared to executive function symptoms (M=19.3; CI=17.6, 20.9). Cancer patients holding a job with both manual and non-manual tasks reported less work-specific cognitive symptoms (unstandardized regression coefficient b=-4.80; CI=-7.76, -1.83) over time, compared to cancer patients with a non-manual job. Over time, higher depressive symptoms were related to experiencing more overall work-specific cognitive symptoms (b=1.27; CI=1.00, 1.55) and a higher fatigue score was related to more working memory symptoms (b=0.13; CI=0.04, 0.23). Job type should be considered when looking at work-specific cognitive symptoms over time in working cancer patients. To reduce work-specific cognitive symptoms, interventions targeted at fatigue and depressive symptoms might be promising. This article is protected by copyright. All rights reserved.

  18. The utility of lymph node mapping sonogram and thyroglobulin surveillance in post thyroidectomy papillary thyroid cancer patients.

    Science.gov (United States)

    Miah, Chowdhury F; Zaman, Jessica A; Simon, Mitchell; Davidov, Tomer; Trooskin, Stanley Z

    2014-12-01

    The American Thyroid Association recommends lymph node mapping (LNM) ultrasonography 6-12 months after thyroidectomy for patients with papillary thyroid cancer (PTC). The yield of LNM over thyroglobulin (TG) screening is not well defined. We sought to investigate this relationship. Post thyroidectomy LNM was performed on 163 patients with PTC. LNM was considered positive based on these criteria: Loss of fatty hilum (LOFH), microcalcifications, hypervascularity, architectural distortion, or short axis (>8 mm). Serum TG levels were compared to LNM and fine needle aspiration (FNA). Sixty-nine patients had suspicious LNM (42%) and 17 had PTC on FNA (25%). There were 135 suspicious lymph nodes described with malignant nodes found in 6 of 65 patients (9%) with LOFH, 13 of 18 patients (76%) with microcalcifications, 11 of 12 patients (92%) with hypervascularity, 16 of 28 patients (52%) with architectural distortion, and 4 of 7 patients (52%) with enlarged size on FNA. The positive predictive value of LNM was 0.34, increasing to 0.66 when LOFH was excluded. Among 152 patients with documented TG data, LNM identified cervical nodal metastasis in 4 patients with TG < 0.5 pg/mL (anti-TG antibody negative, thyroid-stimulating hormone suppressed). Of the 15 patients with positive anti-TG antibody, 3 with recurrence were found on LNM. LNM can detect recurrent PTC when TG level is undetectable, and LOFH is a low-yield sonographic characteristic. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Yoshida, Ken; Takenaka, Tadashi; Tanaka, Eiichi; Kuriyama, Keiko; Yoshida, Mineo; Yamazaki, Hideya; Nishimura, Tsunehiko; Kotsuma, Tadayuki; Fujita, Yuka; Masuda, Norikazu

    2010-01-01

    To evaluate radiation dermatitis objectively in patients with breast cancer who had undergone post-operative radiotherapy after breast-conserving surgery. Skin color (L * , a * , and b * 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 * , a * , 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 * value (darker) at the end of radiotherapy. The Common Toxicity Criteria version 3 scores were found to correlate well with a * and L * 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.)

  20. [Safety and efficacy of docetaxel in prostate cancer patients: based on the post-marketing surveillance in Japan].

    Science.gov (United States)

    Mera, Takeshi; Saijo, Nagahiro; Akaza, Hideyuki

    2012-04-01

    The safety and efficacy of docetaxel in prostate cancer were evaluated based on the results of post-marketing surveillance. 149 patients were enrolled between September 2008 and May 2010. The starting dose of docetaxel was 75 mg/m² in 53 patients(36%), 70 mg/m² in 55 (37%), and ≤ 60 mg/m² in 41(28%). The median number of treatment cycles was 8 (range, 1 to 10). There was no age difference observed in the starting doses and the treatment cycles. The most common ≥ grade 3 adverse drug reactions (ADRs) were neutropenia (71%)and leukocytopenia (51%), and they occurred more frequently in patients receiving ≥ 70 mg/m². However, the multi-variate analyses revealed that ≥ grade 3 ADRs did not correlate with the starting doses. Infection-related events (≥ grade 3) and interstitial pneumonia were observed in 15% and 1% of patients, respectively. Prostate-specific-antigen (PSA) flare appeared in 19% of 95 evaluable patients at median period of 26 days from treatment initiation. It continued with median duration of 39. 5 days. PSA response rate as defined ≥ 50% level decline was 37%(95%confidence interval: 27-47) in evaluable patients. It was low in patients receiving ≤ 60 mg/m² (18%). There was no notable difference between patients with initial dose of 75 and 70 mg/m². Further investigation for the longer term is warranted.

  1. Modern pain neuroscience in clinical practice: applied to post-cancer, paediatric and sports-related pain.

    Science.gov (United States)

    Malfliet, Anneleen; Leysen, Laurence; Pas, Roselien; Kuppens, Kevin; Nijs, Jo; Van Wilgen, Paul; Huysmans, Eva; Goudman, Lisa; Ickmans, Kelly

    In the last decade, evidence regarding chronic pain has developed exponentially. Numerous studies show that many chronic pain populations show specific neuroplastic changes in the peripheral and central nervous system. These changes are reflected in clinical manifestations, like a generalized hypersensitivity of the somatosensory system. Besides a hypersensitivity of bottom-up nociceptive transmission, there is also evidence for top-down facilitation of pain due to malfunctioning of the endogenous descending nociceptive modulatory systems. These and other aspects of modern pain neuroscience are starting to be applied within daily clinical practice. However, currently the application of this knowledge is mostly limited to the general adult population with musculoskeletal problems, while evidence is getting stronger that also in other chronic pain populations these neuroplastic processes may contribute to the occurrence and persistence of the pain problem. Therefore, this masterclass article aims at giving an overview of the current modern pain neuroscience knowledge and its potential application in post-cancer, paediatric and sports-related pain problems. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  2. Long-term costs of introducing HPV-DNA post-treatment surveillance to national cervical cancer screening in Ireland.

    Science.gov (United States)

    Agapova, Maria; Duignan, Andrea; Smith, Alan; O'Neill, Ciaran; Basu, Anirban

    2015-01-01

    Co-testing (cytology plus human papillomavirus DNA testing) as part of cervical cancer surveillance in Ireland increases one-time testing costs. Of interest to policy makers was the long-term impact of these costs accompanied by decreases in intensity of recalls for women with no detected abnormalities. A cost analysis of cytology-only and co-testing strategy was implemented using decision analytic modeling, aggregating testing utilization and costs for each of the two strategies over 12 years. Aggregated incremental costs of the co-testing strategy were positive for the first 3 years but became negative thereafter, generating a cost savings of roughly €20 million in favor of the cytology-only strategy over a 12-year period. Results were robust over a range of sensitivity analyses with respect to discount and attrition rates. This analysis provided valuable information to policy makers contributing to the introduction of co-testing for post-treatment surveillance (PTS) in Ireland.

  3. 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.

  4. Attachment and couple satisfaction as predictors of expressed emotion in women facing breast cancer and their partners in the immediate post-surgery period.

    Science.gov (United States)

    Favez, Nicolas; Cairo Notari, Sarah; Antonini, Tania; Charvoz, Linda

    2017-02-01

    To investigate expressed emotion (EE) in couples facing breast cancer in the immediate post-surgery period. EE may be predictive of psychological disturbances that hinder both partners' capacities to cope with the stress of the disease. Severity of the disease, attachment tendencies, and couple satisfaction were tested as predictors of EE. The design was cross-sectional. Couples (N = 61) were interviewed 2 weeks after the women's breast surgery. Expressed emotion was assessed in women and in partners with the Five-Minute Speech Sample, with a focus on overt and covert criticisms. Self-reported EE, attachment tendencies, and couple satisfaction were assessed with questionnaires. Hierarchical regression analyses were performed to test the predictors and possible interactions between them. Both partners expressed overt and covert criticisms; women expressed more overt criticisms than did their partners. Cancer stage was inversely related to the number of overt criticisms in women and to the number of covert criticisms in partners. Regression analyses showed that in women, higher attachment anxiety and lower couple satisfaction were positive predictors of overt criticisms; in partners, a higher cancer stage was a negative predictor of overt and covert criticisms. Practitioners should pay attention to the couple relationship in breast cancer. EE is most likely to appear when the cancer stage is low, showing that even when the medical prognosis is optimal, relational and emotional disturbances may occur. Statement of contribution What is already known on this subject? The couple relationship is of paramount importance in breast cancer. Expressed emotion (EE) is related to negative individual and relational psychological outcomes in psychiatric and somatic diseases. Expressed emotion has not yet been studied in the context of breast cancer. What does this study add? Expressed emotion is present in breast cancer situations, especially when the cancer stage is low. There

  5. 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

    : The bladder cancer cell lines RT4 and T24, representing low- and high-malignancy grades respectively, were treated with VP16 (10 or 50 microM) and the level of apoptosis determined using a commercial kit. EGFR receptor activity was determined by western blotting using antibodies against phosphorylated EGFR....... The EGFR was either activated by heparin-binding (HB)-EGF (1 nM) or inhibited with the specific EGFR inhibitor gefitinib (1 or 5 microM). The pan-caspase inhibitor Z-VAD (30 microM) was used to test the involvement of caspase activity. RESULTS: Treatment of T24 bladder cancer cells with VP16 (50 micro...... 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...

  6. Analysis of post-operative changes in serum protein expression profiles from colorectal cancer patients by MALDI-TOF mass spectrometry: a pilot methodological study

    Directory of Open Access Journals (Sweden)

    Marsh Simon

    2010-04-01

    Full Text Available Abstract Background Mass spectrometry-based protein expression profiling of blood sera can be used to discriminate colorectal cancer (CRC patients from unaffected individuals. In a pilot methodological study, we have evaluated the changes in protein expression profiles of sera from CRC patients that occur following surgery to establish the potential of this approach for monitoring post-surgical response and possible early prediction of disease recurrence. Methods In this initial pilot study, serum specimens from 11 cancer patients taken immediately prior to surgery and at approximately 6 weeks following surgery were analysed alongside 10 normal control sera by matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS. Using a two-sided t-test the top 20 ranked protein peaks that discriminate normal from pre-operative sera were identified. These were used to classify post-operative sera by hierarchical clustering analysis (Spearman's Rank correlation and, as an independent 'test' dataset, by k-nearest neighbour and weighted voting supervised learning algorithms. Results Hierarchical cluster analysis classified post-operative sera from all six early Dukes' stage (A and B patients as normal. The remaining five post-operative sera from more advanced Dukes' stages (C1 and C2 were classified as cancer. Analysis by supervised learning algorithms similarly grouped all advanced Dukes' stages as cancer, with four of the six post-operative sera from early Dukes' stages being classified as normal (P = 0.045; Fisher's exact test. Conclusions The results of this pilot methodological study illustrate the proof-of-concept of using protein expression profiling of post-surgical blood sera from individual patients to monitor disease course. Further validation on a larger patient cohort and using an independent post-operative sera dataset would be required to evaluate the potential clinical relevance of this approach. Prospective

  7. 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

  8. Icotinib, a selective EGF receptor tyrosine kinase inhibitor, for the treatment of non-small-cell lung cancer.

    Science.gov (United States)

    Tan, Fenlai; Shi, Yuankai; Wang, Yinxiang; Ding, Lieming; Yuan, Xiaobin; Sun, Yan

    2015-01-01

    Advanced non-small-cell lung cancer (NSCLC) is the main cause for cancer-related mortality. Treatments for advanced NSCLC are largely palliative and a benefit plateau appears to have reached with the platinum-based chemotherapy regimens. EGF receptor (EGFR) tyrosine kinase inhibitors gefitinib, erlotinib and afatinib came up with prolonged progression-free survival and improved quality of life, especially in EGFR-mutated patients. Icotinib is an oral selective EGFR tyrosine kinase, which was approved by China Food and Drug administration in June 2011 for treating advanced NSCLC. Its approval was based on the registered Phase III trial (ICOGEN), which showed icotinib is noninferior to gefitinib. This review will discuss the role of icotinib in NSCLC, and its potential application and ongoing investigations.

  9. Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors.

    Science.gov (United States)

    Midtgaard, Julie

    2013-02-01

    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. This theoretical paper aims to outline how researchers and practitioners can draw from Antonovsky's salutogenetic theory and White & Epston's Narrative Therapy to develop and implement intervention efforts centered on promotion of long-term physical activity behaviour, while at the same time increasing the individual cancer survivor's sense of meaning and personal health resources. The Copenhagen PACT (Physical Activity after Cancer Treatment) Study targeting adoption and maintenance of regular physical activity in post-therapy cancer survivors is briefly presented including a brief review of the theoretical rationale behind the psychological component of the intervention, i.e. a narrative-based exercise counselling programme. Subsequently, particular attention is given to the core principles, different components and structure of the counselling manual including sample questions and examples of written documents that have emanated from the individual counselling sessions. The discussion includes consideration of some methodological challenges that arise when attempting to evaluate narrative-based interventions in the context of physical activity promotion in cancer rehabilitation and survivorship care.

  10. Depression, anxiety, post-traumatic stress disorder and health-related quality of life and its association with social support in ambulatory prostate cancer patients.

    Science.gov (United States)

    Mehnert, A; Lehmann, C; Graefen, M; Huland, H; Koch, U

    2010-11-01

    The aim of this study is to identify anxiety, depression and post-traumatic stress disorder in prostate cancer patients and to investigate the association with social support and health-related quality of life. A total of 511 men who had undergone prostatectomy were surveyed during ambulatory follow-up care for an average of 27 months after surgery using standardised self-report measures (e.g. Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist--Civilian Version, Illness-Specific Social Support Scale, Short-Form Health Survey). Seventy-six per cent of patients evaluated their disease as 'not' or a 'little threatening'. The cancer diagnosis and uncertainty were most frequently reported as 'distressing', while medical treatment and doctor-patient interaction were most frequently evaluated as 'most helpful'. The number of patients reporting increased levels of psychological distress was 16%, with 6% demonstrating signs of having severe mental health problems'. No higher levels of anxiety and depression were observed in cancer patients compared with age-adjusted normative comparison groups. Lack of positive support, detrimental interactions and perceived threat of cancer were found to be predictors of psychological co-morbidity (P interactions, threat of cancer, disease stage and age significantly predicted mental health (P social support on physical health was rather weak. Findings emphasise the need for routine psychosocial screening. © 2009 The Authors. European Journal of Cancer Care © 2009 Blackwell Publishing Ltd.

  11. 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

    2014-01-01

    INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether these altera...... and could potentially be used to monitor whether all cancer cells have been removed at surgery and/or, subsequently, whether the patients develop recurrence.......INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether...... these 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...

  12. Post-treatment biopsy results following permanent transrectal ultrasound-guided interstitial brachytherapy in early stage prostate cancer

    International Nuclear Information System (INIS)

    Prestidge, Bradley R.; Blasko, John C.; Grimm, Peter D.; Hoak, David C.; Cavanagh, Bill; Ragde, Haakon

    1995-01-01

    PURPOSE/OBJECTIVE: Although some controversy remains, most authors agree that post-treatment prostatic biopsy is the best measure of local control in prostate cancer. Brachytherapy series reporting post-implant biopsy results have been few in number, limited in size, and involving older open or combined external beam techniques. The present study was undertaken to assess local control rates as determined by post-implant prostate biopsy in a large series of consecutive patients who have received permanent interstitial brachytherapy using a contemporary transrectal ultrasound directed, transperineal, computer generated, volume technique. METHOD/MATERIALS: From January 1988 to January 1994, 402 patients received permanent I-125 (285, 71%) or Pd-103 (117, 29%) interstitial brachytherapy as primary treatment for prostatic carcinoma at the Northwest Tumor Institute. Of these, 201 have consented to prostatic biopsy at least 12 months post-implant with a median follow-up of 40 months (range of 12 to 83 months). None had received hormone manipulation. A total of 361 biopsies were performed on 201 patients with a range of 1 to 6 yearly biopsies per patient; 91 receiving multiple biopsies. The other 201 patients were either unable (for geographic reasons) or unwilling to submit for biopsy. However, all patients with a rising PSA or clinical suspicion of recurrence underwent biopsy when possible. The 201 biopsy patients presented with a median age of 69 (range 47 to 89). Stages included 51 T1 (25%), 125 T2a (62%), 22 T2b (11%), and 3 T2c (1%). Gleason sums included 69 2-4 (34%), 117 5-6 (58%), 15 7-10 (7%), and 2 ungraded (1%). The initial PSA was 6.6 (range 0.7 to 74.6). There was no significant difference in the presenting characteristics or implant parameters between those patients biopsied and those that were not. 143 received I-125 (71%) prescribed to a minimum peripheral dose of 160 Gy with a median activity of 35.5 mCi, and 58 (29%) received Pd-103 prescribed to a

  13. Nrf2 but not autophagy inhibition is associated with the survival of wild-type epidermal growth factor receptor non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Zhou, Yan; Li, Yuan; Ni, Hong-Min; Ding, Wen-Xing; Zhong, Hua

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. Icotinib and Gefitinib are two epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) that have been used to treat NSCLC. While it is well known that mutations of EGFR can affect the sensitivity of NSCLC to the EGFR-TKI, other mechanisms may also be adopted by lung cancer cells to develop resistance to EGFR-TKI treatment. Cancer cells can use multiple adaptive mechanisms such as activation of autophagy and Nrf2 to protect against various stresses and chemotherapeutic drugs. Whether autophagy or Nrf2 activation contributes to the resistance of NSCLC to EGFR-TKI treatment in wild-type EGFR NSCLC cells remains elusive. In the present study, we confirmed that Icotinib and Gefitinib induced apoptosis in EGFR mutant HCC827 but not in EGFR wild-type A549 NSCLC cells. Icotinib and Gefitinib did not induce autophagic flux or inhibit mTOR in A549 cells. Moreover, suppression of autophagy by chloroquine, a lysosomal inhibitor, did not affect Icotinib- or Gefitinib-induced cell death in A549 cells. In contrast, Brusatol, an Nrf2 inhibitor, significantly suppressed the cell survival of A549 cells. However, Brusatol did not further sensitize A549 cells to EGFR TKI-induced cell death. Results from this study suggest that inhibition of Nrf2 can decrease cell vitality of EGFR wild-type A549 cells independent of autophagy. - Highlights: • Cancer cells use adaptive mechanisms against chemotherapy. • Autophagy is not essential for the drug resistance of lung cancer A549 cells. • Inhibition of Nrf2 decreases cell survival of lung cancer A549 cells.

  14. Nrf2 but not autophagy inhibition is associated with the survival of wild-type epidermal growth factor receptor non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan [Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030 (China); Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160 (United States); Li, Yuan; Ni, Hong-Min; Ding, Wen-Xing [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zhong, Hua, E-mail: eddiedong8@hotmail.com [Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030 (China)

    2016-11-01

    Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. Icotinib and Gefitinib are two epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) that have been used to treat NSCLC. While it is well known that mutations of EGFR can affect the sensitivity of NSCLC to the EGFR-TKI, other mechanisms may also be adopted by lung cancer cells to develop resistance to EGFR-TKI treatment. Cancer cells can use multiple adaptive mechanisms such as activation of autophagy and Nrf2 to protect against various stresses and chemotherapeutic drugs. Whether autophagy or Nrf2 activation contributes to the resistance of NSCLC to EGFR-TKI treatment in wild-type EGFR NSCLC cells remains elusive. In the present study, we confirmed that Icotinib and Gefitinib induced apoptosis in EGFR mutant HCC827 but not in EGFR wild-type A549 NSCLC cells. Icotinib and Gefitinib did not induce autophagic flux or inhibit mTOR in A549 cells. Moreover, suppression of autophagy by chloroquine, a lysosomal inhibitor, did not affect Icotinib- or Gefitinib-induced cell death in A549 cells. In contrast, Brusatol, an Nrf2 inhibitor, significantly suppressed the cell survival of A549 cells. However, Brusatol did not further sensitize A549 cells to EGFR TKI-induced cell death. Results from this study suggest that inhibition of Nrf2 can decrease cell vitality of EGFR wild-type A549 cells independent of autophagy. - Highlights: • Cancer cells use adaptive mechanisms against chemotherapy. • Autophagy is not essential for the drug resistance of lung cancer A549 cells. • Inhibition of Nrf2 decreases cell survival of lung cancer A549 cells.

  15. 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

  16. Expression of miRNA-26b-5p and its target TRPS1 is associated with radiation exposure in post-Chernobyl breast cancer.

    Science.gov (United States)

    Wilke, Christina M; Hess, Julia; Klymenko, Sergiy V; Chumak, Vadim V; Zakhartseva, Liubov M; Bakhanova, Elena V; Feuchtinger, Annette; Walch, Axel K; Selmansberger, Martin; Braselmann, Herbert; Schneider, Ludmila; Pitea, Adriana; Steinhilber, Julia; Fend, Falko; Bösmüller, Hans C; Zitzelsberger, Horst; Unger, Kristian

    2018-02-01

    Ionizing radiation is a well-recognized risk factor for the development of breast cancer. However, it is unknown whether radiation-specific molecular oncogenic mechanisms exist. We investigated post-Chernobyl breast cancers from radiation-exposed female clean-up workers and nonexposed controls for molecular changes. Radiation-associated alterations identified in the discovery cohort (n = 38) were subsequently validated in a second cohort (n = 39). Increased expression of hsa-miR-26b-5p was associated with radiation exposure in both of the cohorts. Moreover, downregulation of the TRPS1 protein, which is a transcriptional target of hsa-miR-26b-5p, was associated with radiation exposure. As TRPS1 overexpression is common in sporadic breast cancer, its observed downregulation in radiation-associated breast cancer warrants clarification of the specific functional role of TRPS1 in the radiation context. For this purpose, the impact of TRPS1 on the transcriptome was characterized in two radiation-transformed breast cell culture models after siRNA-knockdown. Deregulated genes upon TRPS1 knockdown were associated with DNA-repair, cell cycle, mitosis, cell migration, angiogenesis and EMT pathways. Furthermore, we identified the interaction partners of TRPS1 from the transcriptomic correlation networks derived from gene expression data on radiation-transformed breast cell culture models and sporadic breast cancer tissues provided by the TCGA database. The genes correlating with TRPS1 in the radiation-transformed breast cell lines were primarily linked to DNA damage response and chromosome segregation, while the transcriptional interaction partners in the sporadic breast cancers were mostly associated with apoptosis. Thus, upregulation of hsa-miR-26b-5p and downregulation of TRPS1 in radiation-associated breast cancer tissue samples suggests these molecules representing radiation markers in breast cancer. © 2017 UICC.

  17. 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.

  18. Cancer Disparities - Cancer Currents Blog

    Science.gov (United States)

    Blog posts on cancer health disparities research—including factors that influence disparities, disparities-related research efforts, and diversity in the cancer research workforce—from NCI Cancer Currents.

  19. Cancer Technology - Cancer Currents Blog

    Science.gov (United States)

    Blog posts on technologies that affect cancer research and care—including new technologies for detecting cancer, testing treatments, storing/analyzing data, and improving patient care—from NCI Cancer Currents.

  20. Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures

    Directory of Open Access Journals (Sweden)

    M. Simó

    Full Text Available No previous event-related potentials (ERPs study has explored the error-related negativity (ERN - an ERP component indexing performance monitoring - associated to cancer and chemotherapy-induced cognitive impairment in a lung cancer population. The aim of this study was to examine differences in performance monitoring in a small-cell lung cancer group (SCLC, C+ 1-month following chemotherapy and two control groups: a non-small cell lung cancer patient group (NSCLC, C− prior to chemotherapy and a healthy control group (HC.Seventeen SCLC (C+ underwent a neuropsychological assessment and an ERP study using a flanker and a stop-signal paradigm. This group was compared to fifteen age-, gender- and education-matched NSCLC (C− and eighteen HC.Between 20 and 30% of patients in both lung cancer groups (C+ and C− met criteria for cognitive impairment. Concerning ERPs, lung cancer patients showed lower overall hit rate and a severe ERN amplitude reduction compared to HC.Lung cancer patients exhibited an abnormal pattern of performance monitoring thus suggesting that chemotherapy and especially cancer itself, may contribute to cognitive deterioration. ERN appeared as an objective laboratory tool sensitive to cognitive dysfunction in cancer population. Keywords: Event-related potentials-ERP, Error-related negativity (ERN, Performance monitoring, Lung cancer, Cognitive impairment, Chemobrain

  1. 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.

  2. Simulation of Post-Thyroidectomy Treatment Alternatives for Triiodothyronine or Thyroxine Replacement in Pediatric Thyroid Cancer Patients

    Science.gov (United States)

    Ben-Shachar, Rotem; Huang, Stephen A.; DiStefano, Joseph J.

    2012-01-01

    Background As in adults, thyroidectomy in pediatric patients with differentiated thyroid cancer is often followed by 131I remnant ablation. A standard protocol is to give normalizing oral thyroxine (T4) or triiodothyronine (T3) after surgery and then withdraw it for 2 to 6 weeks. Thyroid remnants or metastases are treated most effectively when serum thyrotropin (TSH) is high, but prolonged withdrawals should be avoided to minimize hypothyroid morbidity. Methods A published feedback control system model of adult human thyroid hormone regulation was modified for children using pediatric T4 kinetic data. The child model was developed from data for patients ranging from 3 to 9 years old. We simulated a range of T4 and T3 replacement protocols for children, exploring alternative regimens for minimizing the withdrawal period, while maintaining normal or suppressed TSH during replacement. The results are presented with the intent of providing a quantitative basis to guide further studies of pediatric treatment options. Replacement was simulated for up to 3 weeks post-thyroidectomy, followed by various withdrawal periods. T4 vs. T3 replacement, remnant size, dose size, and dose frequency were tested for effects on the time for TSH to reach 25 mU/L (withdrawal period). Results For both T3 and T4 replacement, higher doses were associated with longer withdrawal periods. T3 replacement yielded shorter withdrawal periods than T4 replacement (up to 3.5 days versus 7–10 days). Higher than normal serum T3 concentrations were required to normalize or suppress TSH during T3 monotherapy, but not T4 monotherapy. Larger remnant sizes resulted in longer withdrawal periods if T4 replacement was used, but had little effect for T3 replacement. Conclusions T3 replacement yielded withdrawal periods about half those for T4 replacement. Higher than normal hormone levels under T3 monotherapy can be partially alleviated by more frequent, smaller doses (e.g., twice a day). LT4 may be the

  3. Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development

    DEFF Research Database (Denmark)

    Leeming, D J; Bay-Jensen, A C; Vassiliadis, E

    2011-01-01

    -associated extracellular matrix (ECM) proteins. Furthermore, severe cellular stress and inflammation, caused by cancer, results in generation of PTMs, which will be distributed throughout the ECM. This gives rise to release of protein-specific fragments to the circulation. Here we highlight the importance of remodeling...... of the ECM in cancer and the generation of PTMs, which may be cancer specific and reflect disease progression; thus having potential for biochemical marker development....

  4. Role of antioxidant therapy in ameliorating the side effects of post-operative radiotherapy on genetic material of cancer cervix patients

    International Nuclear Information System (INIS)

    Korraa, S.; Elmaghraby, T.; Arian, F.; Mahfouz, M.

    2003-01-01

    The oxidative stress found in cancer patients and radiotherapy was resulted from the increased production of oxidants in the body and the inefficiency of endogenous antioxidant system to eliminate such oxidants. The present study was carried out to investigated whether supplementation of cancer cervix patients during radiotherapy with antioxidants can ameliorate the damaging effects of radiation on DNA of circulating lymphocytes or not. Accordingly, apoptosis, DNA-fragmentation, lipid peroxidation and the frequency of micronuclei among cancer cervix patient undergoing post-operative radiotherapy (n=40) were measured with and without the administration course of antioxidant antox (including 60 mg vitamin C 10 mg vitamin E, 1000 U I vitamin A and 50 mg selenium). Patients were divided into 2 groups each of 20 patients. The first group was administered the antioxidant antox, 200 mg per day, during radiotherapy and one week more post-cessation of radiotherapy , while the second group did not supplemented with antox. All parameters were investigated in a control group of 20 normal healthy women and in the 40 patient ones

  5. Pre- and post-radiotherapy computed tomography in laryngeal cancer: imaging-based prediction of local failure

    International Nuclear Information System (INIS)

    Pameijer, Frank A.; Hermans, Robert; Mancuso, Anthony A.; Mendenhall, William M.; Parsons, James T.; Stringer, Scott P.; Kubilis, Paul S.; Tinteren, Harm van

    1999-01-01

    Purpose: To determine if pre-radiotherapy (RT) and/or post-radiotherapy computed tomography (CT) can predict local failure in patients with laryngeal carcinoma treated with definitive RT. Methods and Materials: The pre- and post-RT CT examinations of 59 patients (T3 glottic carcinoma [n = 30] and T1-T4 supraglottic carcinoma [n = 29]) were reviewed. For each patient, the first post-RT CT study between 1 and 6 months after irradiation was used. All patients were treated with definitive hyperfractionated twice-daily continuous-course irradiation to a total dose of 6,720-7,920 cGy, and followed-up clinically for at least 2 years after completion of RT. Local control was defined as absence of primary tumor recurrence and a functioning larynx. On the pre-treatment CT study, each tumor was assigned a high-or low-risk profile for local failure after RT. The post-RT CT examinations were evaluated for post-treatment changes using a three-point post-RT CT-score: 1 = expected post-RT changes; 2 = focal mass with a maximal diameter of 1 cm, or < 50% estimated tumor volume reduction. Results: The local control rates at 2 years post-RT based on pre-treatment CT evaluation were 88% for low pre-treatment risk profile patients (95% CI: 66-96%) and 34% (95% CI: 19-50%) for high pre-treatment risk profile patients (risk ratio 6.583; 95% CI: 2.265-9.129; p = 0.0001). Based on post-treatment CT, the local control rates at 2 years post-RT were 94% for score 1, 67% for score 2, and 10% for score 3 (risk ratio 4.760; 95% CI: 2.278-9.950 p 0.0001). Post-RT CT scores added significant information to the pre-treatment risk profiles on prognosis. Conclusions: Pre-treatment CT risk profiles, as well as post-RT CT evaluation can identify patients, irradiated for laryngeal carcinomas, at high risk for developing local failure. When the post-RT CT score is available, it proves to be an even better prognosticator than the pre-treatment CT-risk profile

  6. Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Eiichiro Okazaki

    2017-12-01

    Full Text Available Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ, posterior-superior (PSQ, anterior-inferior (AIQ, and posterior-inferior (PIQ. Predictive factors and cut-off values of biochemical failure-free survival (BFFS and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4% had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

  7. The effect of gender on health-related quality of life and related factors in post-lobectomy lung-cancer patients.

    Science.gov (United States)

    Chang, Nai-Wen; Lin, Kuan-Chia; Hsu, Wen-Hu; Lee, Shih-Chun; Chan, James Yi-Hsin; Wang, Kwua-Yun

    2015-06-01

    While studies have documented gender differences by histologic type among lung cancer patients, the effect of these differences on the health-related quality of life (HRQoL) of post-lobectomy lungcancer patients and related factors remain uncertain. This study examines gender-specific HRQoL and related factors in post-lobectomy lung-cancer patients. A cross-sectional study design was applied. A convenience sample of 231 post-lobectomy lungcancer patients was recruited from the thoracic surgery outpatient departments of two teaching hospitals in Taipei, Taiwan from March to December 2012. Patients performed a spirometry test and completed instruments that included a Beck Depression Inventory-II, an Interpersonal Support Evaluation List, and the symptom and function scales of the Quality of Life Questionnaire. Data analysis used descriptive statistics, including mean and standard deviations, frequency, and percentage values. Independent-sample Student's t-tests and multivariate analyses were used for comparative purposes. This study confirmed a significant gender effect on HRQoL and HRQoL-related factors such as marital status, religious affiliation, smoking status, histologic type, symptoms, pulmonary function, depression, and family support. Moreover, multivariate analysis found gender to be a significant determinant of the HRQoL aspects of physical functioning, emotional functioning, and cognitive functioning. Finally, results indicated that factors other than gender were also significant determinants of HRQoL. Gender impacts the HRQoL and related factors of postoperative lung-cancer patients. Therefore, gender should be considered in assessing and addressing the individual care needs of these patients in order to attain optimal treatment outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Application of Measurements of Serum CA15-3 and B-AKP in Diagnosis of Bone Metastasis in Patients with Post-operative Mammary Cancer

    International Nuclear Information System (INIS)

    Liu Yan; Zhang Xia; Yuan Shiqiang

    2010-01-01

    To evaluate the diagnosis value of serum CA15-3 and B-AKP measurements in diagnosis of bone metastasis images in patients with post-operative mammary cancer, retrospective study on the bone scan images and serum CA15-3 and bone alkaline phosphatase (B-AKP) levels were performed in 92 patients with confirmed post-operative mammary gland cancer. The results showed that the serum levels of CA15-3 and B-AKP were increased step by step significantly along with the advancement of bone metastatic grading from M0 to M3 (P<0.01). The serum levels of CA15-3 and B-AKP were positively correlated with the number of bone metastasis. The positive rate of bone metastasis was 63.2% with serum CA15-3 more than 25U/mL; and the negative predictive value of bone metastasis was 94.5% with serum CA15-3 less than 25U/mL. The positive rate of bone metastasis was 59.6% with serum B-AKP levels more than 20U/L; and the negative predictive value of bone metastasis was 73.5% with serum B-AKP levels less than 20U/L. The negative predictive value of bone metastasis was 100% with serum CA15-3 less than 25U/mL and serum B-AKP levels less than 20U/L. The combined measurement of the serum CA15-3 and B-AKP levels would play an important role in diagnosis of bone scan images in patients with post-operative mammary cancer. (authors)

  9. "I Got My Diagnosis on a Yellow Post-it Note": Young Adult Cancer Patients' Experiences of the Process of Being Diagnosed With Cancer.

    Science.gov (United States)

    Hauken, May Aasebø; Hølge-Hazelton, Bibbi; Larsen, Torill M B

    2018-06-01

    Cancer in young adults is rare but young adult cancer patients (YACPs) are at an increased risk of severe physical and psychosocial impairments during cancer treatment and survivorship. However, little is known about the onset of this process. The aim of this study was to explore how young cancer survivors experience the process of being diagnosed with cancer. A qualitative method founded on a phenomenological-hermeneutical approach was used and included in-depth interviews with 20 young adult survivors (aged 24-35 years) with different cancer diagnoses, analyzed by Systematic Text Condensation. The participants' experiences of the diagnosis process were elaborated according to 3 main themes: (1) "I felt something was wrong, but…," (2) "The traumatic uncertainty," and (3) "The day my world collapsed." The findings indicate that the YACPs experienced a diagnosis of cancer as a highly traumatic and long-lasting process, characterized by lack of information and uncertainty. The findings indicate that healthcare professionals do not acknowledge the vulnerable phase of life and transitional challenges of YACPs. The findings highlight the need to raise awareness of cancer in young adulthood in the public and in the primary healthcare system, to shorten the diagnosis process, and to clarify responsibility for age-related information and psychosocial follow-up during the diagnosis process. Further research is highly warranted.

  10. Quality of life and physical activity in long-term (≥5 years post-diagnosis) colorectal cancer survivors - systematic review.

    Science.gov (United States)

    Eyl, Ruth Elisa; Xie, Kun; Koch-Gallenkamp, Lena; Brenner, Hermann; Arndt, Volker

    2018-06-01

    Due to the increasing number of long-term (≥5 years post diagnosis) colorectal cancer survivors, long-term quality of life of these patients is highly relevant. Several studies have reported a positive association between physical activity and quality of life in colorectal cancer survivors, however, so far no systematic review has been published which focuses on long-term colorectal cancer survivors. A systematic review was conducted using the databases PubMed, Web of Science, PsychINFO, and CINAHL. Studies which investigated associations between physical activity and quality of life in long-term colorectal cancer survivors were included. Ten articles based on seven studies were identified. Long-term colorectal cancer survivors who were physically active reported better quality of life than long-term survivors who were not physically active. Both, moderate to vigorous physical activity and lower levels like light physical activity were associated with higher quality of life. Most studies assessed the association between physical activity and quality of life cross-sectionally but one prospective study which measured physical activity and quality of life at three different points in time also found associations between physical activity and quality of life. The association between physical activity and quality of life seemed to be stronger among women than among men. The findings of this systematic review support an association between physical activity and quality of life in long-term colorectal cancer survivors. However, the evidence is limited as most studies were based on cross-sectional and observational design.

  11. Trait anxiety as an independent predictor of poor health-related quality of life and post-traumatic stress symptoms in rectal cancer

    Science.gov (United States)

    Ristvedt, Stephen L.; Trinkaus, Kathryn M.

    2009-01-01

    Objectives To determine the influence of trait anxiety on patient reports of health-related quality of life (HRQoL) and post-traumatic stress symptoms (PTSS) in a sample of rectal cancer survivors. Design Eighty patients who had been diagnosed with rectal cancer were assessed at two points in time in a longitudinal study. Methods At Time 1, soon after initial treatment, participants completed the State-Trait Anxiety Inventory and the Temperament and Character Inventory Harm Avoidance scale, which were combined into a composite measure of trait anxiety. At Time 2, 2-5 years following Time 1, participants were assessed for HRQoL using the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) and for PTSS using the Impact of Event Scale-Revised (IES-R). Results HRQoL and PTSS were generally favourable on average, although many of the patients reported faring poorly. Higher levels of trait anxiety were predictive of poorer scores on all of the FACT-C and the IES-R total and subscale measures. More severe faecal incontinence was associated with poorer scores on the FACT Emotional well-being subscale, the FACT-Colorectal Cancer Scale, and all of the IES-R scales. Males were more likely than females to have poorer scores on the FACT Social well-being subscale, and those patients who were further out from active treatment had more favourable scores on the FACT-Colorectal Cancer Scale. The presence of a colostomy did not impact HRQoL or PTSS. Conclusion Trait anxiety had a significant influence on HRQoL and PTSS several years following diagnosis and treatment of rectal cancer. PMID:19171084

  12. Perceived cognitive impairment in Chinese patients with breast cancer and its relationship with post-traumatic stress disorder symptoms and fatigue.

    Science.gov (United States)

    Li, Jie; Yu, Lixiang; Long, Zhouting; Li, Yang; Cao, Fenglin

    2015-06-01

    Clinical reports have shown that adjuvant chemotherapy has a negative impact on perceived cognitive impairment (PCI) of patients with breast cancer; however, evidence concerning the effects of psychological factors such as post-traumatic stress disorder (PTSD) symptoms on PCI is limited, especially in relation to Chinese patients with breast cancer. This research investigated the associations between psychological factors and PCI in Chinese women with breast cancer. In total, 204 women with breast cancer were assessed for PCI, PTSD symptoms, fatigue, anxiety, and depression using self-report measures. Hierarchical linear regression was conducted to investigate the associations between the variables of interest and PCI. Two hundred and two women were included in the final analysis; two of those originally tested were excluded because of missing data. A univariate analysis showed that PCI was significantly related to education, PTSD symptoms (re-experience, avoidance, and hyperarousal), fatigue, depression, anxiety, and undergoing chemotherapy or radiotherapy. Hierarchical linear regression revealed that PTSD symptoms and fatigue (ΔR(2)  = 0.26, P fatigue are important risk factors for significant PCI and are therefore worthy of further investigation. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Feasibility of an expressive-disclosure group intervention for post-treatment colorectal cancer patients: results of the Healthy Expressions study.

    Science.gov (United States)

    Carmack, Cindy L; Basen-Engquist, Karen; Yuan, Ying; Greisinger, Anthony; Rodriguez-Bigas, Miguel; Wolff, Robert A; Barker, Trina; Baum, George; Pennebaker, James W

    2011-11-01

    Adjusting to cancer requires effective cognitive and emotional processing. Written and verbal disclosure facilitate processing and have been studied independently in cancer survivors. Combined written and verbal expression may be more effective than either alone, particularly for patients with difficult to discuss or embarrassing side effects. Thus, the authors developed and tested the efficacy of a 12-session combined written and verbal expression group program for psychologically distressed colorectal cancer (CRC) patients. Forty post-treatment patients with CRC (stages I-III) identified as psychologically distressed using the Brief Symptom Inventory (BSI) were randomized to an intervention group (Healthy Expressions; n = 25) or standard care (control group; n = 15). Assessments were completed at baseline, Month 2, and Month 4 (postintervention). Primary outcomes were psychological functioning and quality of life (QOL). Most participants were women (63%), white (63%), and non-Hispanic (75%). The Healthy Expressions group demonstrated significantly greater changes in distress compared with the control group at Month 2 on the BSI Global Severity Index (GSI) and the Centers for Epidemiologic Studies Depression scale (CES-D) scores (P psychological functioning in CRC patients who reported experiencing distress. Findings demonstrate the program's feasibility and provide strong support for conducting a larger randomized trial. Copyright © 2011 American Cancer Society.

  14. Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model.

    Science.gov (United States)

    Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

    2017-01-01

    Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms.

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

    Science.gov (United States)

    Taylor, Cath; Sippitt, Joanna M; Collins, Gary; McManus, Chris; Richardson, Alison; Dawson, Jeremy; Richards, Michael; Ramirez, Amanda J

    2010-06-29

    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. 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. 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. 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 tackling these issues may have improved working lives further.

  16. The molecular cues for the biological effects of ionizing radiation dose and post-irradiation time on human breast cancer SKBR3 cell line: A Raman spectroscopy study.

    Science.gov (United States)

    Jafarzadeh, Naser; Mani-Varnosfaderani, Ahmad; Gilany, Kambiz; Eynali, Samira; Ghaznavi, Habib; Shakeri-Zadeh, Ali

    2018-03-01

    Radiotherapy is one of the main modalities of cancer treatment. The utility of Raman spectroscopy (RS) for detecting the distinct radiobiological responses in human cancer cells is currently under investigation. RS holds great promises to provide good opportunities for personalizing radiotherapy treatments. Here, we report the effects of the radiation dose and post-irradiation time on the molecular changes in the human breast cancer SKBR3 cells, using RS. The SKBR3 cells were irradiated by gamma radiation with different doses of 0, 1, 2, 4, and 6 Gy. The Raman signals were acquired 24 and 48 h after the gamma radiation. The collected Raman spectra were analyzed by different statistical methods such as principal component analysis, linear discriminant analysis, and genetic algorithm. A thorough analysis of the obtained Raman signals revealed that 2 Gy of gamma radiation induces remarkable molecular and structural changes in the SKBR3 cells. We found that the wavenumbers in the range of 1000-1400 cm -1 in Raman spectra are selective for discriminating between the effects of the different doses of irradiation. The results also revealed that longer post-irradiation time leads to the relaxation of the cells to their initial state. The molecular changes that occurred in the 2Gy samples were mostly reversible. On the other hand, the exposure to doses higher than 4Gy induced serious irreversible changes, mainly seen in 2700-2800 cm -1 in Raman spectra. The classification models developed in this study would help to predict the radiation-based molecular changes induced in the cancer cells by only using RS. Also, this designed framework may facilitate the process of biodosimetry. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

    Science.gov (United States)

    Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

    2012-11-01

    Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

  18. Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment.

    Science.gov (United States)

    Mothes, A R; Runnebaum, M; Runnebaum, I B

    2018-05-01

    First evaluation of dual-phase vaginal Er:YAG laser to omit hormonal treatment for atrophy-related symptoms in post-menopausal breast cancer survivors following prolapse surgery. Patients with a history of breast cancer at the time of surgery for pelvic organ prolapse were offered non-hormonal vaginal Er:YAG laser treatment when complaining of atrophy-related genitourinary syndrome of menopause. A single 10-min course of dual-phase protocol of pulsed Er:YAG laser (2940 nm, fractional ablative and thermal mode, fluence according to tissue thickness). Follow-up included subjective satisfaction, vaginal pH, vaginal health index (VHI), and complications after 6 weeks. A total of 16 breast cancer survivors (age 71 years, SD 7) had been seeking treatment for pelvic floor symptoms related to vaginal atrophy at follow-up visits after prolapse surgery. All ablative vaginal Er:YAG laser outpatient procedures were successfully completed, all patients returned to daily activities without a need for analgetic medication. Evaluation was performed after 8.3 (SD 2.5) weeks. Pre-laser VHI scored 16 (SD 4.6) and post-laser VHI 20 (SD 3) with p = 0.01. Patients were satisfied in 94% (n = 15) regarding symptom relief. Breast cancer survivors with atrophy-related complaints after pelvic floor surgery may benefit from vaginal application of this innovative dual protocol of Er:YAG laser technology as a non-hormonal treatment approach.

  19. Pattern of External Breast Prosthesis Use by Post Mastectomy Breast Cancer Patients in India: Descriptive Study from Tertiary Care Centre

    OpenAIRE

    Ramu, D.; Ramesh, Rakesh S.; Manjunath, Suraj; Shivakumar; Goel, Vipin; Hemnath, G. N.; Alexander, Annie

    2015-01-01

    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 wom...

  20. Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers

    International Nuclear Information System (INIS)

    Mahajan, Abhishek; Engineer, Reena; Chopra, Supriya; Mahanshetty, Umesh; Juvekar, S.L.; Shrivastava, S.K.; Desekar, Naresh; Thakur, M.H.

    2015-01-01

    •In operated cervix cancer, the accuracy of diagnosing vaginal vault/local recurrent lesions was higher at combined multiparametric MR imaging and conventional MR imaging (100%) than at conventional MR imaging (70%) or multiparametric MR imaging (96.7%) alone.•We found a significant correlation between percentage tumor regression and pre-treatment parameters: NEI (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction present in the pretherapy MRI (p = 0.01).•Multiparametric and BOLD hypoxia MR Imaging are feasible and reliable in diagnosing post-operative recurrence in cervical cancer and should be applied when there is clinical suspicion of post-operative recurrence.•Quantitative image features obtained at multiparametric-MRI with BOLD hypoxia imaging has potential to be an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future. In operated cervix cancer, the accuracy of diagnosing vaginal vault/local recurrent lesions was higher at combined multiparametric MR imaging and conventional MR imaging (100%) than at conventional MR imaging (70%) or multiparametric MR imaging (96.7%) alone. We found a significant correlation between percentage tumor regression and pre-treatment parameters: NEI (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction present in the pretherapy MRI (p = 0.01). Multiparametric and BOLD hypoxia MR Imaging are feasible and reliable in diagnosing post-operative recurrence in cervical cancer and should be applied when there is clinical suspicion of post-operative recurrence. Quantitative image features obtained at multiparametric-MRI with BOLD hypoxia imaging has potential to be an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future. To assess the diagnostic value of multiparametric-MRI (MPMRI) with hypoxia imaging as a functional marker for characterizing and detecting

  1. 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)

    Krauss, Daniel J.; Hu, Chen; Bahary, Jean-Paul; Souhami, Luis; Gore, Elizabeth M.; Chafe, Susan Maria Jacinta; Leibenhaut, Mark H.; Narayan, Samir; Torres-Roca, Javier; Michalski, Jeff; Zeitzer, Kenneth L.; Donavanik, Viroon; Sandler, Howard; McGowan, David G.; Jones, Christopher U.; Shipley, William U.

    2015-01-01

    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

  2. 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

    2011-01-01

    . Conclusions: Performance and reporting of pelvic MRI in rectal cancer patients can be improved significantly through multidisciplinary development courses and on-site-visits while improvements in image interpretation with regard to treatment stratification may demand more intensive efforts....

  3. 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)

    Paterson, M.C.; Aubin, R.A.; Fourney, R.M.; Mirzayans, R.

    1989-01-01

    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)

  4. A case of likely radiation-induced synchronous esophageal and skin carcinoma following post-operative radiation for breast cancer

    International Nuclear Information System (INIS)

    Kanogawa, Naoya; Shimada, Hideaki; Kainuma, Osamu; Cho, Akihiro; Yamamoto, Hiroshi; Itami, Makiko; Nagata, Matsuo

    2009-01-01

    A 71-year-old woman was admitted in January 2008 with on upper thoracic esophageal squamous cell carcinoma and a right chest wall skin tumor. When she was 32 years old, she had a radical mastectomy for right breast cancer and received postoperative radiation. Due to the presence of lung adhesions, trans-thoracic esophagectomy could not be done; thus, a blunt dissection was performed. She was discharged on the 19 th postoperative day. On pathology, a pT2N0M0 (pStage II) esophageal tumor was diagnosed. A resection of her skin tumor underwent 79 days after the esophageal surgery; on pathology, the skin tumor was diagnosed as a basal cell carcinoma. Since the esophageal tumor and the skin tumor occurred in the same area that had received radiation therapy, these tumors were diagnosed as being radiation-induced secondary tumors. In the English language medical literature, several reports of radiation-induced esophageal cancer occurring as a second cancer after radiotherapy for breast cancer have been published. Radiation-induced esophageal cancer rates may increase in Japan given the number of women who previously received radiotherapy for breast cancer. (author)

  5. Learning and memory performance in breast cancer survivors 2 to 6 years post-treatment: the role of encoding versus forgetting.

    Science.gov (United States)

    Root, James C; Andreotti, Charissa; Tsu, Loretta; Ellmore, Timothy M; Ahles, Tim A

    2016-06-01

    Our previous retrospective analysis of clinically referred breast cancer survivors' performance on learning and memory measures found a primary weakness in initial encoding of information into working memory with intact retention and recall of this same information at a delay. This suggests that survivors may misinterpret cognitive lapses as being due to forgetting when, in actuality, they were not able to properly encode this information at the time of initial exposure. Our objective in this study was to replicate and extend this pattern of performance to a research sample to increase the generalizability of this finding in a sample in which subjects were not clinically referred for cognitive issues. We contrasted learning and memory performance between breast cancer survivors on endocrine therapy 2 to 6 years post-treatment with age- and education-matched healthy controls. We then stratified lower- and higher-performing breast cancer survivors to examine specific patterns of learning and memory performance. Contrasts were generated for four aggregate visual and verbal memory variables from the California Verbal Learning Test-2 (CVLT-2) and the Brown Location Test (BLT): Single-trial Learning: Trial 1 performance, Multiple-trial Learning: Trial 5 performance, Delayed Recall: Long-delay Recall performance, and Memory Errors: False-positive errors. As predicted, breast cancer survivors' performance as a whole was significantly lower on Single-trial Learning than the healthy control group but exhibited no significant difference in Delayed Recall. In the secondary analysis contrasting lower- and higher-performing survivors on cognitive measures, the same pattern of lower Single-trial Learning performance was exhibited in both groups, with the additional finding of significantly weaker Multiple-trial Learning performance in the lower-performing breast cancer group and intact Delayed Recall performance in both groups. As with our earlier finding of weaker initial

  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

    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.......021). Conclusion. Anti-depressant effects could be caused by exercise in self-referred cancer patients undergoing chemotherapy. Dedicated trials and follow-up studies are needed to clarify the optimal duration and content of exercise interventions to meet the needs of clinically depressive or anxious patients....... 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...

  7. Post site metastasis of breast cancer after video-assisted thoracic surgery for pulmonary metastasis of breast cancer: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mee Hyun; Hwang, Ji Young; Hyun, Su Jeong; Lee, Yul; Woo, Ji Young; Yang, Ik; Hong, Hye Sook; Kim, Han Myun [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2016-05-15

    We reported a case of port site metastasis in a 57-year-old patient who underwent video-assisted thoracic surgery (VATS) resection of pulmonary metastasis from breast cancer. Port site metastasis after VATS is very rare in patients with breast cancer. However, when suspicious lesions are detected near the port site in patients who have undergone VATS for pulmonary metastasis, port site metastasis should be considered in the differential diagnosis.

  8. 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.

    Science.gov (United States)

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

    2015-03-11

    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. Cross-sectional tracking surveys conducted pre-intervention and post-intervention (waves I and III of campaign). Western Australia. 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 III (n=155) of the campaign. The 'Alcohol and Cancer' mass media campaign ran from May 2010 to May 2011 and consisted of three waves of paid television advertising with supporting print advertisements. Campaign awareness; knowledge of drinking guidelines and the link between alcohol and cancer; intentions towards drinking. Prompted recognition of the campaign increased from 67% following wave I to 81% following wave III (adjusted OR (adj OR)=2.31, 95% CI 1.33 to 4.00, p=0.003). Improvements in women's knowledge that drinking alcohol on a regular basis increases cancer risk were found following wave I (adj OR=2.60, 95% CI 1.57 to 4.30, pawareness of links between alcohol and cancer, and knowledge of drinking guidelines. However, a single campaign may be insufficient to measurably curb drinking behaviour in a culture where pro-alcohol social norms and product marketing are pervasive. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. 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)

    Garabalino, M.A.; Heber, E.M.; Monti, Hughes A.; Molinari, A.J.; Pozzi, E.C.C.; Trivillin, V.A.; Schwint, Amanda E.

    2011-01-01

    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

  10. Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

    Science.gov (United States)

    de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

    2017-04-01

    Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced

  11. 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.

  12. Polychromatic light (480-3400nm) similar to the terrestrial solar spectrum without its UV component in post-surgical immunorehabilitation of breast cancer patients.

    Science.gov (United States)

    Zhevago, Natalia A; Zimin, Alexander A; Glazanova, Tatyana V; Davydova, Natalia I; Bychkova, Natalia V; Chubukina, Zhanna V; Buinyakova, Anna I; Ballyuzek, Marina F; Samoilova, Kira A

    2017-01-01

    To this day, two methods of phototherapy (PT) have been successfully used in post-surgical immunorehabilitation of patients with breast cancer (BC): intravenous laser irradiation of the patients' blood and reinfusion of lympholeukosuspension of BC patients after single irradiation with HeNe laser. The objective of this pilot experimental study was to verify the effectiveness of the percutaneous use of polychromatic visible light combined with polychromatic infrared (pVIS+pIR) radiation similar to the major components of natural solar spectrum in post-surgical management of BC patients. Patients with BC (adenocarcinoma) of I-II stages, n=19 who had undergone mastectomy, were divided into 2 groups. The control group of patients (n=8) underwent a conventional course of post-surgical rehabilitation and sham irradiation. Patients of the PT group (n=11) additionally received 7days of daily treatment with polychromatic light on the sacral area, D=15cm. The PT course began on the day after mastectomy (Bioptron-2 device; Switzerland, 480-3400nm, 95% polarization, 40mW/cm 2 , 24J/cm 2 ). Mastectomy produced many changes in cellular and humoral immunity, which was recorded on the 1st and 8th post-surgical days. The PT course resulted in a faster normalization of post-surgical leukocytosis and activation of cytotoxic CD8 + T-lymphocytes (Lym), reduced the elevated concentration in blood of immune complexes and in parallel promoted cytotoxic activity of CD16 + /CD56 + NK-cells. The PT up-regulated the number of NK-cells in patients with its decrease on the 1st post-surgical day and prevented the decrease in the amount of monocytes, CD19 + B-Lym, CD3 + T-Lym, CD4 + T-helpers, activated CD3 + /HLADR + T-Lym, and the decrease of the phagocytotic capability of neutrophils. PT blocked the down-regulation of the IgM, IgA concentration and abnormally sharp increase of the proinflammatory cytokine IFN-γ content. Therefore, a 7-day course with polychromatic light prevented the

  13. THE CHANGES OF PHYSICAL AND PSYCHOLOGICAL SEXUAL COMPLAINS IN WOMEN WITH POST TREATMENT CERVICAL CANCER AFTER SEXUAL NURSING INTERVENTION

    Directory of Open Access Journals (Sweden)

    Afiyanti Afiyanti

    2017-04-01

    Full Text Available Introduction: Despite increasing awareness related to sexual health for cervical cancer survivors, health care providers are passive in addressing their sexual issues. The objectives were to develop and investigate the effect of a sexual nursing intervention packet to mitigate sexual dysfunction among cervical cancer survivors. Method: A sample of 104 survivors were participated consecutively based on required inclusive criteria in this quasi-experimental study. The sexual nursing intervention packet focused on the physical, psychological, and care of relational aspects of sexual health elements. The packet consisted of 6 weekly 2-hour sessions. Results: The participants reported poor sexual satisfaction and sexual function. There were no statistically signi fi cant differences in sexual interest, sexual arousal, orgasm, and vaginal lubrication improvement following the intervention, although all the variables in the intervention group were improved clinically. The sexual nursing intervention packet was effective in increasing sexual satisfaction and decreasing dispareunia among cervical cancer survivors. Discussion: This study suggests that the quality of life in cervical cancer survivors could be improved with the sexual nursing intervention packet provided as part of supportive group care. This program may be more effective if delivered earlier and for a longer period. Implications for Practice: The sexual nursing intervention packet offers an opportunity to facilitate small-group dynamics that lay the ground for further contacts leading to earlier recognition of sexual problems and active involvement for sexual health improvement for cervical cancer survivors and nurses. It could be utilized for survivor education or support groups to increase sexual satisfaction following cancer treatment.

  14. 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.

  15. 'Pizza, patients and points of view': Involving young people in the design of a post registration module entitled the adolescent with cancer.

    Science.gov (United States)

    Fallon, Sue; Smith, Joanna; Morgan, Sue; Stoner, Mandy; Austin, Catriona

    2008-03-01

    Health policy and education directives emphasise the need to involve service users and carers in healthcare, from service design and delivery to the education of healthcare professionals. This paper describes a pilot project aimed at eliciting teenagers and young people with cancer views in relation to the content of a continuing professional development module entitled 'adolescents with cancer'. Seven young people participated in the project. The project design was based on the PARTICIPATION - spice it up [Shephard, C., Treseder, P., 2002. spice it up! Dynamix, Swansea] framework, which aims to ensure effective and appropriate involvement of service users and carers. 'Post-it ideas storm' 'diamond ranking' and 'dot voting' were used to elicit the young people's views. The teenagers and young people could clearly articulate the qualities they felt nurses should have when caring for adolescents with cancer. They also identified topics they felt were important to include in the module, with an understanding of, and using, humour being given the highest priority. This was not originally included in the module timetable but as a direct result of consulting with the young people changes were made to reflect their views.

  16. BAG3 promotes proliferation of ovarian cancer cells via post-transcriptional regulation of Skp2 expression.

    Science.gov (United States)

    Yan, Jing; Liu, Chuan; Jiang, Jing-Yi; Liu, Hans; Li, Chao; Li, Xin-Yu; Yuan, Ye; Zong, Zhi-Hong; Wang, Hua-Qin

    2017-10-01

    Bcl-2 associated athanogene 3 (BAG3) contains a modular structure, through which BAG3 interacts with a wide range of proteins, thereby affording its capacity to regulate multifaceted biological processes. BAG3 is often highly expressed and functions as a pro-survival factor in many cancers. However, the oncogenic potential of BAG3 remains not fully understood. The cell cycle regulator, S-phase kinase associated protein 2 (Skp2) is increased in various cancers and plays an important role in tumorigenesis. The current study demonstrated that BAG3 promoted proliferation of ovarian cancer cells via upregulation of Skp2. BAG3 stabilized Skp2 mRNA via its 3'-untranslated region (UTR). The current study demonstrated that BAG3 interacted with Skp2 mRNA. In addition, miR-21-5p suppressed Skp2 expression, which was compromised by forced BAG3 expression. These results indicated that at least some oncogenic functions of BAG3 were mediated through posttranscriptional regulation of Skp2 via antagonizing suppressive action of miR-21-5p in ovarian cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Improvement of orthopedic dental treatment of patients suffering post-surgery defects of the maxilla of cancer genesis

    Directory of Open Access Journals (Sweden)

    A. S. Arutyunov

    2015-01-01

    Full Text Available The paper presents a comprehensive study identifying the key issuesand giving the mathematical, and clinical and microbiological substantiation of modern principles of providing orthopedic dental care to patients with acquired defects of the upper jaw of cancer genesis.

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

    Directory of Open Access Journals (Sweden)

    Pauwels Evelyn

    2012-10-01

    Full Text Available 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 process included quantitative and qualitative assessments of survivors’ and partners’ care needs and preferences. Participants’ use and evaluation of the website were explored by conducting baseline and post-measurements. During the intervening 10–12 weeks 57 survivors and 28 partners were granted access to the website. Results Fifty-seven percent (n=21 of survivors who took part in the post-measurement indicated that they had visited the website. Compared to non-visitors (n=16, they were more likely to have a partner and a higher income, reported higher levels of self-esteem and had completed treatment for a longer period of time. Partners who consulted the on-line information (42%, n=8 were younger and reported lower levels of social support compared to partners who did not visit the website (n=11. Visitors generally evaluated the content and lay-out positively, yet some believed the information was incomplete and impersonal. Conclusions The website reached only about half of survivors and partners, yet was mostly well-received. Besides other ways of providing information and support, a website containing clear-cut and tailored information could be a useful tool in post-treatment care provision.

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

    Science.gov (United States)

    2012-01-01

    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 process included quantitative and qualitative assessments of survivors’ and partners’ care needs and preferences. Participants’ use and evaluation of the website were explored by conducting baseline and post-measurements. During the intervening 10–12 weeks 57 survivors and 28 partners were granted access to the website. Results Fifty-seven percent (n=21) of survivors who took part in the post-measurement indicated that they had visited the website. Compared to non-visitors (n=16), they were more likely to have a partner and a higher income, reported higher levels of self-esteem and had completed treatment for a longer period of time. Partners who consulted the on-line information (42%, n=8) were younger and reported lower levels of social support compared to partners who did not visit the website (n=11). Visitors generally evaluated the content and lay-out positively, yet some believed the information was incomplete and impersonal. Conclusions The website reached only about half of survivors and partners, yet was mostly well-received. Besides other ways of providing information and support, a website containing clear-cut and tailored information could be a useful tool in post-treatment care provision. PMID:23034161

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

    Science.gov (United States)

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

    2012-10-03

    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. The development process included quantitative and qualitative assessments of survivors' and partners' care needs and preferences. Participants' use and evaluation of the website were explored by conducting baseline and post-measurements. During the intervening 10-12 weeks 57 survivors and 28 partners were granted access to the website. Fifty-seven percent (n=21) of survivors who took part in the post-measurement indicated that they had visited the website. Compared to non-visitors (n=16), they were more likely to have a partner and a higher income, reported higher levels of self-esteem and had completed treatment for a longer period of time. Partners who consulted the on-line information (42%, n=8) were younger and reported lower levels of social support compared to partners who did not visit the website (n=11). Visitors generally evaluated the content and lay-out positively, yet some believed the information was incomplete and impersonal. The website reached only about half of survivors and partners, yet was mostly well-received. Besides other ways of providing information and support, a website containing clear-cut and tailored information could be a useful tool in post-treatment care provision.

  1. Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model

    Science.gov (United States)

    Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

    2017-01-01

    Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms. PMID:28475593

  2. Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model.

    Directory of Open Access Journals (Sweden)

    Chunli Liu

    Full Text Available Post-traumatic stress disorder (PTSD symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C, Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI, and Resilience Scale-14 (RS-14. 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P < 0.01. Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms.

  3. Impact of low-level laser therapy on hyposalivation, salivary pH, and quality of life in head and neck cancer patients post-radiotherapy.

    Science.gov (United States)

    Palma, Luiz Felipe; Gonnelli, Fernanda Aurora Stabile; Marcucci, Marcelo; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Roberto Araújo; Segreto, Helena Regina Comodo

    2017-05-01

    Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm 2 , 30 mW, illuminated area 0.04 cm 2 , 7.5 J/cm 2 , 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p quality of life questionnaire (p patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

  4. 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

  5. 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)

    Versmessen, Harijati; Vinh-Hung, Vincent; Van Parijs, Hilde; Miedema, Geertje; Voordeckers, Mia; Adriaenssens, Nele; Storme, Guy; De Ridder, Mark

    2012-01-01

    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

  6. Providing guidance for genomics-based cancer treatment decisions: insights from stakeholder engagement for post-prostatectomy radiation therapy.

    Science.gov (United States)

    Abe, James; Lobo, Jennifer M; Trifiletti, Daniel M; Showalter, Timothy N

    2017-08-24

    Despite the emergence of genomics-based risk prediction tools in oncology, there is not yet an established framework for communication of test results to cancer patients to support shared decision-making. We report findings from a stakeholder engagement program that aimed to develop a framework for using Markov models with individualized model inputs, including genomics-based estimates of cancer recurrence probability, to generate personalized decision aids for prostate cancer patients faced with radiation therapy treatment decisions after prostatectomy. We engaged a total of 22 stakeholders, including: prostate cancer patients, urological surgeons, radiation oncologists, genomic testing industry representatives, and biomedical informatics faculty. Slides were at each meeting to provide background information regarding the analytical framework. Participants were invited to provide feedback during the meeting, including revising the overall project aims. Stakeholder meeting content was reviewed and summarized by stakeholder group and by theme. The majority of stakeholder suggestions focused on aspects of decision aid design and formatting. Stakeholders were enthusiastic about the potential value of using decision analysis modeling with personalized model inputs for cancer recurrence risk, as well as competing risks from age and comorbidities, to generate a patient-centered tool to assist decision-making. Stakeholders did not view privacy considerations as a major barrier to the proposed decision aid program. A common theme was that decision aids should be portable across multiple platforms (electronic and paper), should allow for interaction by the user to adjust model inputs iteratively, and available to patients both before and during consult appointments. Emphasis was placed on the challenge of explaining the model's composite result of quality-adjusted life years. A range of stakeholders provided valuable insights regarding the design of a personalized decision

  7. Efficacy of Mindfulness-Based Cognitive Therapy on Late Post-Treatment Pain in Women Treated for Primary Breast Cancer: A Randomized Controlled Trial.

    Science.gov (United States)

    Johannsen, Maja; O'Connor, Maja; O'Toole, Mia Skytte; Jensen, Anders Bonde; Højris, Inger; Zachariae, Robert

    2016-10-01

    To assess the efficacy of mindfulness-based cognitive therapy (MBCT) for late post-treatment pain in women treated for primary breast cancer. A randomized wait list-controlled trial was conducted with 129 women treated for breast cancer reporting post-treatment pain (score ≥ 3 on pain intensity or pain burden assessed with 10-point numeric rating scales). Participants were randomly assigned to a manualized 8-week MBCT program or a wait-list control group. Pain was the primary outcome and was assessed with the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2), the Present Pain Intensity subscale (the McGill Pain Questionnaire), and perceived pain intensity and pain burden (numeric rating scales). Secondary outcomes were quality of life (World Health Organization-5 Well-Being Index), psychological distress (the Hospital Depression and Anxiety Scale), and self-reported use of pain medication. All outcome measures were assessed at baseline, postintervention, and 3-month and 6-month follow-up. Treatment effects were evaluated with mixed linear models. Statistically significant time × group interactions were found for pain intensity (d = 0.61; P = .002), the Present Pain Intensity subscale (d = 0.26; P = .026), the SF-MPQ-2 neuropathic pain subscale (d = 0.24; P = .036), and SF-MPQ-2 total scores (d = 0.23; P = .036). Only pain intensity remained statistically significant after correction for multiple comparisons. Statistically significant effects were also observed for quality of life (d = 0.42; P = .028) and nonprescription pain medication use (d = 0.40; P = .038). None of the remaining outcomes reached statistical significance. MBCT showed a statistically significant, robust, and durable effect on pain intensity, indicating that MBCT may be an efficacious pain rehabilitation strategy for women treated for breast cancer. In addition, the effect on neuropathic pain, a pain type reported by women treated for breast cancer, further suggests the potential of MBCT but

  8. Variations in CT determination of target volume with active breath co-ordinate in radiotherapy for post-operative gastric cancer.

    Science.gov (United States)

    Li, Gui-Chao; Zhang, Zhen; Ma, Xue-Jun; Yu, Xiao-Li; Hu, Wei-Gang; Wang, Jia-Zhou; Li, Qi-Wen; Liang, Li-Ping; Shen, Li-Jun; Zhang, Hui; Fan, Ming

    2016-01-01

    To investigate interobserver and inter-CT variations in using the active breath co-ordinate technique in the determination of clinical tumour volume (CTV) and normal organs in post-operative gastric cancer radiotherapy. Ten gastric cancer patients were enrolled in our study, and four radiation oncologists independently determined the CTVs and organs at risk based on the CT simulation data. To determine interobserver and inter-CT variation, we evaluated the maximum dimensions, derived volume and distance between the centres of mass (CMs) of the CTVs. We assessed the reliability in CTV determination among the observers by conformity index (CI). The average volumes ± standard deviation (cm(3)) of the CTV, liver, left kidney and right kidney were 674 ± 138 (range, 332-969), 1000 ± 138 (range, 714-1320), 149 ± 13 (range, 104-183) and 141 ± 21 (range, 110-186) cm(3), respectively. The average inter-CT distances between the CMs of the CTV, liver, left kidney and right kidney were 0.40, 0.56, 0.65 and 0.6 cm, respectively; the interobserver values were 0.98, 0.53, 0.16 and 0.15 cm, respectively. In the volume size of CTV for post-operative gastric cancer, there were significant variations among multiple observers, whereas there was no variation between different CTs. The slices in which variations more likely occur were the slices of the lower verge of the hilum of the spleen and porta hepatis, then the paraoesophageal lymph nodes region and abdominal aorta, and the inferior vena cava, and the variation in the craniocaudal orientation from the interobserver was more predominant than that from inter-CT. First, this is the first study to evaluate the interobserver and inter-CT variations in the determination of the CTV and normal organs in gastric cancer with the use of the active breath co-ordinate technique. Second, we analysed the region where variations most likely occur. Third, we investigated the influence of interobserver variation on

  9. Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck.

    Science.gov (United States)

    Patel, Sapna A; Parvathaneni, Aarthi; Parvathaneni, Upendra; Houlton, Jeffrey J; Karni, Ron J; Liao, Jay J; Futran, Neal D; Méndez, Eduardo

    2017-09-01

    Our primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). We conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. The tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. Surgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability. Published by Elsevier Ltd.

  10. 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

  11. Low Preoperative Prognostic Nutritional Index Predicts Poor Survival Post-gastrectomy in Elderly Patients with Gastric Cancer.

    Science.gov (United States)

    Sakurai, Katsunobu; Tamura, Tatsuro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2016-10-01

    Preoperative nutritional status may predict short- and long-term outcomes of patients with cancer. The aim of this study was to clarify the impact of preoperative nutritional status on outcomes of elderly patients who have undergone gastrectomy for gastric cancer (GC). A review examining 147 patients treated for GC by gastrectomy at our institution between January 2004 and December 2011 was conducted. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cutpoint to stratify patients by high (PNI > 43.8; n = 84) or low (PNI ≤ 43.8; n = 63) nutritional status. Clinicopathologic features and short- and long-term outcomes, including the cause of death, were compared. In multivariate analysis, low PNI was identified as an independent correlate of poor 5-year overall survival (OS). In subgroup analysis, 5-year OS rates for patients with stage 1 GC were significantly worse in the low PNI (vs. high PNI) patient subset, which also posed a significantly higher risk of death from other disease; however, 5-year cancer-specific survival and PNI were unrelated. Deaths from recurrence in both groups were statistically similar, and morbidity rates did not differ significantly by group. PNI is useful in predicting long-term outcomes of elderly patients surgically treated for GC, helping to identify those at high risk of death from other disease. In an effort to improve patient outcomes, nutritional status and oncologic staging merit attention.

  12. 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

  13. [Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

    Science.gov (United States)

    Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

    2016-09-01

    Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    Directory of Open Access Journals (Sweden)

    Verduyn S

    2012-09-01

    Full Text Available Abstract Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC patients with an activating mutation in the epidermal growth factor receptor (EGFR. Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+. From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis; pemetrexed/cisplatin (Pem/Cis; paclitaxel/carboplatin (Pac/Carb in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS. Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS (mean, (95% credibility interval was 5.2 months (4.5; 5.8 for Gem/Cis, 5.3 months (4.6; 6.1 for Pem/Cis; 4.9 months (4.4; 5.5 for Pac/Carb and 8

  15. Dosimetric planning study for the prevention of anal complications after post-operative whole pelvic radiotherapy in cervical cancer patients with hemorrhoids.

    Science.gov (United States)

    Baek, J G; Kim, E C; Kim, S K; Jang, H

    2015-01-01

    Radiation-induced anal toxicity can be induced by low radiation doses in patients with haemorrhoids. The object of this study was to determine the dosimetric benefits of different whole pelvic radiotherapy (WPRT) techniques in terms of dose delivered to the anal canal in post-operative patients with cervical cancer. The planning CT images of 10 patients with cervical cancer undergoing postoperative radiotherapy were used for comparison of three different plans. All patients had been treated using the conventional box technique WPRT (CV-WPRT), and we tried low-margin-modified WPRT (LM-WPRT), three-dimensional conformal techniques WPRT (CF-WPRT) and intensity-modulated WPRT (IM-WPRT) planning for dosimetric comparison of the anal canal, retrospectively. Mean anal canal doses of the IM-WPRT were significantly lower (p 99%, and the proportion that received ≥108% of the prescribed dose for IM-WPRT was <2%. Volumes of bladders and rectums that received ≥30 or ≥40 Gy were significantly lower for IM-WPRT than for three of the four-field WPRT plans (p = 0.000). IM-WPRT can significantly reduce radiation dose delivered to the anal canal and does not compromise PTV coverage. In patients with haemorrhoids, IM-WPRT may be of value for the prevention of anal complications. Although tolerance of the anal canal tends to be ignored in patients undergoing post-operative WPRT, patients with haemorrhoids may suffer complications at low radiation doses. The present study shows IM-WPRT can be meaningful in these patients.

  16. Effects of an Oral Elemental Nutritional Supplement on Post-gastrectomy Body Weight Loss in Gastric Cancer Patients: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Imamura, Hiroshi; Nishikawa, Kazuhiro; Kishi, Kentaro; Inoue, Kentaro; Matsuyama, Jin; Akamaru, Yusuke; Kimura, Yutaka; Tamura, Shigeyuki; Kawabata, Ryohei; Kawada, Junji; Fujiwara, Yoshiyuki; Kawase, Tomono; Fukui, Junichi; Takagi, Mari; Takeno, Atsushi; Shimokawa, Toshio

    2016-09-01

    Post-gastrectomy weight loss is associated with deterioration in quality of life, and influences the long-term prognosis of gastric cancer patients. We conducted a prospective, randomized controlled, open-label study to examine whether an oral elemental diet (Elental(®), Ajinomoto Pharmaceuticals, Tokyo, Japan; hereafter referred to as ED) prevents postoperative weight loss in post-gastrectomy patients. Patients were randomly divided to receive the ED or control diet. The ED group received 300 kcal of ED plus their regular diet for 6-8 weeks after surgery, starting from the day the patient started a soft rice or equivalent diet after surgery, while the control group received the regular diet alone. The primary endpoint was the percentage of body weight loss (%BWL) from the presurgical body weight to that at 6-8 weeks after surgery. Secondary endpoints were dietary adherence, nutrition-related blood parameters, and adverse events. This study included 112 patients in eight hospitals. The mean treatment compliance rate in the ED group was 68.7 ± 30.4 % (median 81.2 %). The %BWL was significantly different between the ED and control groups (4.86 ± 3.72 vs. 6.60 ± 4.90 %, respectively; p = 0.047). In patients who underwent total gastrectomy, the %BWL was significantly different between the two groups (5.03 ± 3.65 vs. 9.13 ± 5.43 %, respectively; p = 0.012). In multivariate analysis, ED treatment, surgery type, and preoperative performance status were independently associated with %BWL. No significant differences were observed in the other clinical variables. ED supplementation reduced postoperative weight loss in gastric cancer patients undergoing gastrectomy.

  17. SU-E-T-14: A Feasibility Study of Using Modified AP Proton Beam for Post-Operative Pancreatic Cancer Therapy

    International Nuclear Information System (INIS)

    Ding, X; Witztum, A; Kenton, O; Younan, F; Dormer, J; Kremmel, E; Lin, H; Liu, H; Tang, S; Both, S; Kassaee, A; Avery, S

    2014-01-01

    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

  18. Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Joanne W. [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Guzzo, Thomas J.; Wein, Alan J. [Department of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Haas, Naomi B. [Department of Medical Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Both, Stefan [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Vapiwala, Neha, E-mail: vapiwala@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    2012-08-01

    Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in

  19. Personal resilience resources predict post-stem cell transplant cancer survivors' psychological outcomes through reductions in depressive symptoms and meaning-making.

    Science.gov (United States)

    Campo, Rebecca A; Wu, Lisa M; Austin, Jane; Valdimarsdottir, Heiddis; Rini, Christine

    2017-01-01

    This longitudinal study examined whether post-transplant cancer survivors (N = 254, 9 months to 3 years after stem cell transplant treatment) with greater personal resilience resources demonstrated better psychological outcomes and whether this could be attributed to reductions in depressive symptoms and/or four meaning-making processes (searching for and finding reasons for one's illness; searching for and finding benefit from illness). Hierarchical linear regression analyses examined associations of survivors' baseline personal resilience resources (composite variable of self-esteem, mastery, and optimism), which occurred an average of 1.7 years after transplant, and 4-month changes in psychological outcomes highly relevant to recovering from this difficult and potentially traumatic treatment: post-traumatic stress disorder (PTSD) symptoms and purpose in life. Boot-strapped analyses tested mediation. Greater personal resilience resources predicted decreases in PTSD stress symptoms (b = -0.07, p = 0.005), mediated by reductions in depressive symptoms (b = -0.01, 95% CI: -0.027, -0.003) and in searching for a reason for one's illness (b = -0.01, 95% CI: -0.034, -0.0003). In addition, greater resilience resources predicted increases in purpose in life (b = 0.10, p meaning-making (searching for a reason for one's illness) was also important for reducing PTSD symptoms.

  20. Metabolic Response on Post-therapy FDG-PET Predicts Patterns of Failure After Radiotherapy for Cervical Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Grigsby, Perry W.

    2012-01-01

    Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy 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.

  1. Incidental finding of ovarian teratoma on post-therapy scan for papillary thyroid cancer and impact of SPECT/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jammah, Anwar Ali, E-mail: dranwarjammah@hotmail.com [Department of Medicine, King Saud University, Riyadh (Saudi Arabia); Driedger, Albert; Rachinsky, Irina [Department of Nuclear Medicine, University of Western Ontario, (Canada)

    2011-10-15

    A 41-year old woman post thyroidectomy and neck dissection is presented in this case. She initially presented goiter and an enlarged cervical lymph node. She had no family history of cancer or radiation therapy. She had total thyroidectomy and found to have papillary thyroid cancer (T4N1M0). Histopathology report revealed multifocal classical papillary thyroid carcinoma with lymphovascular invasion, extra-thyroidal extension, and positive lymph nodes. She was treated with 6.5 Gigabecquerel (GBq) of {sup 131}Iodine. Whole-body scan showed uptake in the neck and large focus in the left lower abdomen. Single-photon emission computed tomography SPECT/CT demonstrated a round shaped mass in the left pelvis. Pathology revealed cystic teratoma with benign thyroid tissue (struma ovarii), and no malignancy. Two months later, she had the second treatment with 5.5 GBq {sup 131}Iodine. Her follow-up stimulated and non-stimulated thyroglobulin levels were significantly lower, and there was no abnormal uptake in the follow- -up scan (author)

  2. [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.

  3. World War II-related post-traumatic stress disorder and breast cancer risk among Israeli women: a case-control study.

    Science.gov (United States)

    Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

    2014-03-01

    Several studies have suggested that post-traumatic stress disorder (PTSD) is related to adverse health outcomes. There are limited data on PTSD and cancer, which has a long latency period. We investigated the association between World War II (WWII)-related PTSD and subsequent breast cancer (BC) risk among Jewish WWII survivors and examined whether this association was modified by exposure to hunger during WWII. We compared 65 BC patients diagnosed in 2005 through 2010 to 200 population-based controls who were members of various organizations for Jewish WWII survivors in Israel. All participants were born in Europe, lived at least six months under Nazi rule during WWII, and immigrated to Israel after the war. We estimated PTSD using the PTSD Inventory and applied logistic regression models to estimate the association between WWII-related PTSD and BC, adjusting for potential confounders. We observed a linear association between WWII-related PTSD and BC risk. This association remained significant following adjustment for potential confounders, including obesity, alcohol consumption, smoking, age during WWII, hunger exposure during WWII, and total number of traumatic life events (OR = 2.89, 95% CI = 1.14-7.31). However, the level of hunger exposure during WWII modified this effect significantly. These findings suggest an independent association between WWII-related PTSD and subsequent BC risk in Jewish WWII survivors that is modified by hunger, a novel finding. Future research is needed to further explore these findings.

  4. Development and evaluation of a holistic surgical head and neck cancer post-treatment follow-up clinic using touchscreen technology-Feasibility study.

    Science.gov (United States)

    Semple, C J; Lannon, D; Qudairat, E; McCaughan, E; McCormac, R

    2018-03-01

    The efficacy of traditional follow-up care is being challenged, as cancer survivors' supportive and psychological needs are often neither identified, nor addressed. This study's aim was to develop a holistic surgical follow-up clinic for oral and oropharyngeal cancer patients were participants completed a disease-specific health-related quality of life tool (UWQOLv4) and item prompt list (Patient Concern Inventory) on a touchscreen computer. Information generated was used to focus the consultation on patient's identified needs and concerns. By means of a prospective non-randomised, pre-test post-test design, this follow-up clinic was evaluated using the patient enablement instrument (PEI) and patient content checklist (PCC). Feasibility was explored from the patient perspective (satisfaction survey) and clinician perspective (qualitative interview). Forty-four consecutive patients were recruited. Findings demonstrating five of the eight topics (overall QOL, emotions, head and neck symptoms, side-effects of treatment, chronic non-specific) on PCC were discussed more frequently, but changes were not statistically significant. The PEI highlighted a trend towards perceived improvement in four of the six items. Using touchscreen computers to aid communication during routine follow-up was reported as both feasible and beneficial by patients and clinicians. Providing a patient-focused follow-up consultation can facilitate the identification of unmet needs, permitting timely and appropriate intervention being initiated. © 2018 John Wiley & Sons Ltd.

  5. 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

    2015-01-01

    Roč. 54, č. 9 (2015), 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: 4.722, year: 2015

  6. First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

    Science.gov (United States)

    Tang, Derek H; Li, Nanxin; Du, Ella X; Peeples, Miranda; Chu, Lihao; Xie, Jipan; Barghout, Victoria

    2017-12-01

    This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient populatio