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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.

    Science.gov (United States)

    Bernsdorf, Mogens; Balslev, Eva; Lykkesfeldt, Anne E; Kroman, Niels; Harder, Eva; von der Maase, Hans; Jakobsen, Erik H; Grabau, Dorthe; Ejlertsen, Bent

    2011-07-01

    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 ErbB 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 invasive breast cancer ≥ 2 cm. Material from patients randomized and completing treatment (four cycles of neoadjuvant EC plus 12 weeks of either gefitinib or placebo) in the NICE trial having available ER status both at baseline and after neoadjuvant treatment were eligible for this study. Tumors 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 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 in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors.

  2. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells.

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    Mei-Chuan Tang

    Full Text Available Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, are effective for non-small cell lung cancer (NSCLC patients with EGFR mutations. However, these patients eventually develop resistance to EGFR-TKI. The goal of the present study was to investigate the involvement of autophagy in gefitinib resistance. We developed gefitinib-resistant cells (PC-9/gef from PC-9 cells (containing exon 19 deletion EGFR after long-term exposure in gefitinib. PC-9/gef cells (B4 and E3 were 200-fold more resistant to gefitinib than PC-9/wt cells. Compared with PC-9/wt cells, both PC-9/gefB4 and PC-9/gefE3 cells demonstrated higher basal LC3-II levels which were inhibited by 3-methyladenine (3-MA, an autophagy inhibitor and potentiated by chloroquine (CQ, an inhibitor of autophagolysosomes formation, indicating elevated autophagy in PC-9/gef cells. 3-MA and CQ concentration-dependently inhibited cell survival of both PC-9wt and PC-9/gef cells, suggesting that autophagy may be pro-survival. Furthermore, gefitinib increased LC3-II levels and autolysosome formation in both PC-9/wt cells and PC-9/gef cells. In PC-9/wt cells, CQ potentiated the cytotoxicity by low gefitinib (3 nM. Moreover, CQ overcame the acquired gefitinib resistance in PC-9/gef cells by enhancing gefitinib-induced cytotoxicity, activation of caspase 3 and poly (ADP-ribose polymerase cleavage. Using an in vivo model xenografting with PC-9/wt and PC-9/gefB4 cells, oral administration of gefitinib (50 mg/kg completely inhibited the tumor growth of PC-9/wt but not PC-9/gefB4cells. Combination of CQ (75 mg/kg, i.p. and gefitinib was more effective than gefitinib alone in reducing the tumor growth of PC-9/gefB4. Our data suggest that inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the ErbB rec...... in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors.......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...

  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

    The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor a (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the ErbB rec...... in a small but significant fraction of patients and should, whenever possible, be performed following neoadjuvant chemotherapy for ER negative breast cancer. Gefitinib did not affect the reversion rate of ER negative tumors.......The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor a (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the Erb......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...

  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

    BACKGROUND: Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer wh...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  8. Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed.

    Science.gov (United States)

    2004-10-01

    (1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.

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

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    Yukihiro Yano

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  12. Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib

    Institute of Scientific and Technical Information of China (English)

    HUANG Yi-sheng; HUANG Biao; WU Yi-long

    2011-01-01

    The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments.There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months.The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy,so it was suspected that the leukoencephalopathy was associated with gefitinib.

  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. 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.

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

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

    2011-01-01

    a significant difference in pCR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups....... Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer a parts per thousand yen 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint...

  16. 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

    CR between triple negative breast cancer (TNBC) and non-TNBC tumors (P = 0.03). More patients in the gefitinib arm had hematological toxicity (P = 0.15) and discontinued treatment (9/94 vs. 2/86) because of adverse events (AE). Tumor response rates were similar in the two groups. A significantly higher p....... Women with unilateral, primary operable, estrogen receptor negative invasive breast cancer = 2 cm were eligible for inclusion. Randomized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib (250 mg daily) or placebo. Primary endpoint was pathologic complete response...

  17. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Platinum-based chemotherapy can improve the survival and quality of life of patients with locally advanced and metastatic lung cancer. Second-line docetaxel monotherapy can improve overall survival following the failure of first line chemotherapy. However, many limiting factors such as poor performance status, advanced age, adverse effects of chemotherapy and reluctance to receive cytotoxic chemotherapeutic agents render patients unable to accept chemotherapy. Furthermore, for patients who have failed second-line chemotherapy treatment options are often limited to best support care or palliative radiotherapy. 1 Gefitinib (Iressa) is a HER1/EGFR (epidermal growth factor receptor)- tyrosine kinase inhibitor approved in a number of countries including the US, Japan and recently China for the treatment of patients with non-small cell lung cancer (NSCLC), who have failed platinum/docetaxel-based first line and second line chemotherapy. 2,3 Current data show heterogeneity in response to gefitinib among people of different ethnic origin, but there is very little data concerning the safety and efficacy of gefitinib in Chinese patients. This paper aims to summarize the safety and efficacy data for gefitinib 250 mg treatment in Chinese NSCLC patients at Peking Union Medical College Hospital who received gefitinib as part of an Expanded Access Programme.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  19. Metabolism of the EGFR tyrosin kinase inhibitor gefitinib by cytochrome P450 1A1 enzyme in EGFR-wild type non small cell lung cancer cell lines

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    Alfieri Roberta R

    2011-11-01

    Full Text Available Abstract Background Gefitinib is a tyrosine kinase inhibitor (TKI of the epidermal growth factor receptor (EGFR especially effective in tumors with activating EGFR gene mutations while EGFR wild-type non small cell lung cancer (NSCLC patients at present do not benefit from this treatment. The primary site of gefitinib metabolism is the liver, nevertheless tumor cell metabolism can significantly affect treatment effectiveness. Results In this study, we investigated the intracellular metabolism of gefitinib in a panel of EGFR wild-type gefitinib-sensitive and -resistant NSCLC cell lines, assessing the role of cytochrome P450 1A1 (CYP1A1 inhibition on gefitinib efficacy. Our results indicate that there is a significant difference in drug metabolism between gefitinib-sensitive and -resistant cell lines. Unexpectedly, only sensitive cells metabolized gefitinib, producing metabolites which were detected both inside and outside the cells. As a consequence of gefitinib metabolism, the intracellular level of gefitinib was markedly reduced after 12-24 h of treatment. Consistent with this observation, RT-PCR analysis and EROD assay showed that mRNA and activity of CYP1A1 were present at significant levels and were induced by gefitinib only in sensitive cells. Gefitinib metabolism was elevated in crowded cells, stimulated by exposure to cigarette smoke extract and prevented by hypoxic condition. It is worth noting that the metabolism of gefitinib in the sensitive cells is a consequence and not the cause of drug responsiveness, indeed treatment with a CYP1A1 inhibitor increased the efficacy of the drug because it prevented the fall in intracellular gefitinib level and significantly enhanced the inhibition of EGFR autophosphorylation, MAPK and PI3K/AKT/mTOR signalling pathways and cell proliferation. Conclusion Our findings suggest that gefitinib metabolism in lung cancer cells, elicited by CYP1A1 activity, might represent an early assessment of gefitinib

  20. Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations.

    Science.gov (United States)

    Ichihara, Eiki; Hotta, Katsuyuki; Takigawa, Nagio; Kudo, Kenichiro; Kato, Yuka; Honda, Yoshihiro; Hayakawa, Hiromi; Minami, Daisuke; Sato, Akiko; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2013-09-01

    Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250 mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5 m(2). The median progression-free survival (PFS) of the patients with higher BSA (≥1.5 m(2)) was significantly worse than that of those with lower BSA (BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78-2.89; p = 0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p = 0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR-mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR-mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.

  1. Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer

    OpenAIRE

    2016-01-01

    Abstract Abstract Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in...

  2. 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.

  3. Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.

    Science.gov (United States)

    Melisi, Davide; Caputo, Rosa; Damiano, Vincenzo; Bianco, Roberto; Veneziani, Bianca Maria; Bianco, A Raffaele; De Placido, Sabino; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-12-01

    Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  5. Recurrence patterns of advanced non-small cell lung cancer treated with gefitinib

    Institute of Scientific and Technical Information of China (English)

    CHEN Min-jiang; ZHONG Wei; ZHANG Li; ZHAO Jing; LI Long-yun; WANG Meng-zhao

    2013-01-01

    Background Gefitinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC).However,only a small number of reports have described initial failure sites in patients treated with gefitinib.The aim of this study was to investigate survival,recurrence sites,and treatment after recurrence in these patients.Methods A retrospective review was conducted of all patients with stage Ⅲ/Ⅳ NSCLC treated with gefitinib in Peking Union Medical College Hospital from October 2002 to September 2011.Patient characteristics,initial failure sites,associated clinical factors,and subsequent therapy were included in the analysis of prognostic factors.Results A total of 316 patients were identified The median progress free survival (PFS) and overall survival (OS) times were 238 days and 468 days,respectively.The median survival time after progression was 145 days.The sites of initial failure were lung (62.34%),bone (17.72%),central nerve system (CNS,16.14%),liver (9.49%),and others (7.19%).Patients with single-site progression or multi-site progression were 81.01% and 18.99%,respectively.Progression-free survival time was associated with lung and bone failure.Additionally,the median survival time after progression was lower in patients with multi-site progression and liver progression.Other initial failure sites displayed no relationship with survival,including CNS failure.Subsequent therapy may affect survival after progression.In patients receiving continuous epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy,chemotherapy,radiotherapy,and retreatment with EGFR-TKIs,survival time after progression was prolonged compared with the best supportive care.Conclusions Our data suggest that patients receiving gefltinib should be closely monitored regarding lung metastasis during follow-up.Liver metastases and multi-site progression were poor prognostic factors.After failure with gefltinib,patients may benefit from radiotherapy

  6. Evaluation of [{sup 18}F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Su, Helen; Seimbille, Yann; Ferl, Gregory Z.; Bodenstein, Claudia; Fueger, Barbara; Kim, Kevin J.; Hsu, Yu-Tien; Phelps, Michael E. [UCLA, Department of Molecular Medicine and Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); Dubinett, Steven M. [UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA (United States); Czernin, Johannes [UCLA, Department of Molecular Medicine and Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); UCLA, Ahmanson Biological Imaging Center, David Geffen School of Medicine, Los Angeles, CA (United States); Weber, Wolfgang A. [UCLA, Department of Molecular Medicine and Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); UCLA, Ahmanson Biological Imaging Center, David Geffen School of Medicine, Los Angeles, CA (United States); University of Freiburg, Abteilung Nuklearmedizin, Freiburg (Germany)

    2008-06-15

    Gefitinib, an inhibitor of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK), has shown potent effects in a subset of patients carrying specific EGFR-TK mutations in advanced non-small-cell lung cancer. In this study, we asked whether PET with [{sup 18}F]gefitinib may be used to study noninvasively the pharmacokinetics of gefitinib in vivo and to image the EGFR status of cancer cells. Synthesis of [{sup 18}F]gefitinib has been previously described. The biodistribution and metabolic stability of [{sup 18}F]gefitinib was assessed in mice and vervet monkeys for up to 2 h post injection by both micropositron emission tomography (PET)/computed tomography (CT) scans and postmortem ex vivo tissue harvesting. Uptake levels of radiolabeled gefitinib in EGFR-expressing human cancer cell lines with various levels of EGFR expression or mutation status were evaluated both in vivo and in vitro. MicroPET/CT scans in two species demonstrated a rapid and predominantly hepatobiliary clearance of [{sup 18}F]gefitinib in vivo. However, uptake levels of radiolabeled gefitinib, both in vivo and in vitro, did not correlate with EGFR expression levels or functional status. This unexpected observation was due to high nonspecific, nonsaturable cellular uptake of gefitinib. The biodistribution of the drug analogue [{sup 18}F]gefitinib suggests that it may be used to assess noninvasively the pharmacokinetics of gefitinib in patients by PET imaging. This is of clinical relevance, as insufficient intratumoral drug concentrations are considered to be a factor for resistance to gefitinib therapy. However, the highly nonspecific cellular binding of [{sup 18}F]gefitinib may preclude the use of this imaging probe for noninvasive assessment of EGFR receptor status in patients. (orig.)

  7. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

    OpenAIRE

    Schuler, M.; Yang, J. C.-H.; Park, K.; Kim, J. -H.; Bennouna, J; Chen, Y.-M.; Chouaid, C.; de Marinis, F.; Feng, J. -F.; Grossi, F; Kim, D.-W.; Liu, X.; Lu, S.; Strausz, J.; Vinnyk, Y.

    2015-01-01

    Background Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods Patients with relapsed/refractory disease following ≥1 ...

  8. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-30

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

  11. A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin (IFOX) in Previously Untreated Patients with Metastatic Colorectal Cancer

    Science.gov (United States)

    Fisher, George A.; Kuo, Timothy; Ramsey, Meghan; Schwartz, Erich; Rouse, Robert V.; Cho, Cheryl D.; Halsey, Joanne; Sikic, Branimir I.

    2008-01-01

    Purpose: To investigate the IFOX regimen (gefitinib, 5-fluorouracil [5-FU], leucovorin and oxaliplatin) as first-line therapy in patients with metastatic colorectal cancer. Experimental Design: Eligible patients had stage IV colorectal adenocarcinoma, and had not received prior chemotherapy for metastatic disease. Each cycle consisted of 14 days. Cycle 1 consisted of FOLFOX-4 (oxaliplatin, leucovorin, and 5-FU). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg PO daily throughout the 14 days cycle. Results: Forty-five patients were enrolled and are assessable for toxicity. Forty-three patients are assessable for response. Thirty-one of the 43 patients (72%), had either a complete or partial response by RECIST criteria. Median overall survival was 20.5 months. Median time to progression was 9.3 months. Commonly encountered grade 3/4 toxicities included diarrhea in 67% of patients and neutropenia in 60%. Grade 2 acneiform skin rash typical of gefitinib occurred in 60% of patients. Conclusions: IFOX is an active first-line regimen in patients with metastatic colorectal adenocarcinoma, demonstrating higher response rates but also increased toxicities compared with FOLFOX-4 alone in a similar patient population. PMID:18981005

  12. 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.

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-04-15

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

  15. Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib.

    Science.gov (United States)

    Irwin, Mary E; Mueller, Kelly L; Bohin, Natacha; Ge, Yubin; Boerner, Julie L

    2011-09-01

    Epidermal growth factor receptor (EGFR) is overexpressed in many cancer types including ~30% of breast cancers. Several small molecule tyrosine kinase inhibitors (TKIs) targeting EGFR have shown clinical efficacy in lung and colon cancers, but no benefit has been noted in breast cancer. Thirteen EGFR expressing breast cancer cell lines were analyzed for response to EGFR TKIs. Seven were found to be EGFR TKI resistant; while shRNA knockdown of EGFR determined that four of these cell lines retained the requirement of EGFR protein expression for growth. Interestingly, EGFR localized to plasma membrane lipid rafts in all four of these EGFR TKI-resistant cell lines, as determined by biochemical raft isolation and immunofluorescence. When lipid rafts were depleted of cholesterol using lovastatin, all four cell lines were sensitized to EGFR TKIs. In fact, the effects of the cholesterol biosynthesis inhibitors and gefitinib were synergistic. While gefitinib effectively abrogated phosphorylation of Akt- and mitogen-activated protein kinase in an EGFR TKI-sensitive cell line, phosphorylation of Akt persisted in two EGFR TKI-resistant cell lines, however, this phosphorylation was abrogated by lovastatin treatment. Thus, we have shown that lipid raft localization of EGFR correlates with resistance to EGFR TKI-induced growth inhibition and pharmacological depletion of cholesterol from lipid rafts decreases this resistance in breast cancer cell lines. Furthermore, we have presented evidence to suggest that when EGFR localizes to lipid rafts, these rafts provide a platform to facilitate activation of Akt signaling in the absence of EGFR kinase activity.

  16. Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways.

    Science.gov (United States)

    Xiao, Xiangling; He, Zhongwei; Cao, Wei; Cai, Fen; Zhang, Liang; Huang, Qiuyue; Fan, Chunsheng; Duan, Chao; Wang, Xiaobo; Wang, Jiu; Liu, Ying

    2016-06-01

    Oridonin (Ori), a diterpenoid compound extracted from traditional medicinal herbs, elicits antitumor effects on many cancer types. However, whether Ori can be used in gefitinib-resistant non-small cell lung cancer (NSCLC) cells remains unclear. This study investigated the antitumor activity and underlying mechanisms of Ori. Results demonstrated that this compound dose-dependently inhibited the proliferation, invasion, and migration of the gefitinib-resistant NSCLC cells in vitro. Ori also significantly downregulated the phosphorylation of EGFR, ERK, Akt, expression levels of matrix metalloproteinase-12 (MMP-12), and the cancerous inhibitor of protein phosphatase 2A (CIP2A). In addition, Ori upregulated protein phosphatase 2A (PP2A) activity of gefitinib-resistant NSCLC cells. Ori combined with docetaxel synergistically inhibited these cells. Ori also inhibited tumor growth in murine models. Immunohistochemistry results further revealed that Ori downregulated phospho-EGFR, MMP-12, and CIP2A in vivo. These findings indicated that Ori can inhibit the proliferation, invasion, and migration of gefitinib-resistant NSCLC cells by suppressing EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signaling pathways. Thus, Ori may be a novel effective candidate to treat gefitinib-resistant NSCLC.

  17. Safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.

    Science.gov (United States)

    Hotta, Katsuyuki; Ueoka, Hiroshi; Kiura, Katsuyuki; Tabata, Masahiro; Ogino, Atsuko; Umemura, Shigeki; Harita, Shingo; Gemba, Kenichi; Yonei, Toshiro; Bessho, Akihiro; Maeda, Tadashi; Tanimoto, Mitsune

    2005-01-01

    We evaluated the safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer (NSCLC). We retrospectively compared toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with the same outcomes in patients aged younger than 75 years. In total, 350 patients were eligible for this analysis, of whom 92 were in the elderly group and 258 in the non-elderly group. In the elderly group, adverse events were generally mild to moderate and grade 3-4 adverse events were observed in 8 (9%) patients. The objective response rate (17 vs. 21% for elderly vs. non-elderly, respectively) and median survival time (7.6 vs. 9.3 months) were also similar in the two groups. Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). In this study, treatment with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patients.

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

    Directory of Open Access Journals (Sweden)

    Taira,Naruto

    2006-02-01

    Full Text Available

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

  19. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yuan Y

    2014-05-01

    Full Text Available Ying Yuan, Xiao-Fen Li, Jia-Qi Chen, Cai-Xia Dong, Shan-Shan Weng, Jian-Jin HuangDepartment of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaAbstract: Past studies have demonstrated that epidermal growth factor receptor (EGFR tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC and sensitive EGFR gene mutations. Gefitinib (Iressa®, the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood–brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.Keywords: gefitinib, non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

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

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  2. Gefitinib ('Iressa', ZD1839) may restore chemosensitivity in NSCLC patients?

    Science.gov (United States)

    Fujiwara, Keiichi; Kiura, Katsuyuki; Gemba, Kenichi; Ogata, Yoshiko; Hotta, Katsuyuki; Kishino, Daizo; Tabata, Masahiro; Ueoka, Hiroshi; Tanimoto, Mitsune

    2005-01-01

    Gefitinib ('Iressa, ZD1839) has promising antitumor activity in non-small cell lung cancer (NSCLC). However, patients with advanced NSCLC have few treatment options available if they are refractory to gefitinib. We describe four cases of patients with advanced NSCLC who previously responded to gefitinib and obtained significant tumor regression through retreatment with other cytotoxic agents. Gefitinib might restore chemosensitivity to previously chemorefractory patients.

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

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    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

  4. Role of gefitinib in the targeted treatment of non-small-cell lung cancer in Chinese patients

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    Li MJ

    2016-03-01

    Full Text Available Meng-Jiao Li, Qing He, Mei Li, Feng Luo, Yong-Song Guan Department of Oncology, Center of Oncology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Abstract: Non-small-cell lung cancer (NSCLC is the most common type of lung cancer. Conventional treatment options have limited efficacy because most cases are in the advanced stage at the time of diagnosis. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown its good antitumor activities in treating NSCLC in a number of studies. This paper reviews its role in the targeted treatment of NSCLC in Chinese patients. Keywords: pulmonary carcinoma, therapy, EGFR-TK inhibitor, status, People’s Republic of China 

  5. The influence of autologous cytokine-induced killer cell treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shuxian Qu; Zhaozhe Liu Co-first author; Zhendong Zheng; Zhenyu Ding; Tao Han; Fang Guo; Jianing Qiu; Xiaodong Xie ; Dongchu Ma 

    2015-01-01

    Objective The aim of the study was to observe the influence of autologous cytokine-induced kil er cel (CIK) treatment on the objective ef icacy and safety of gefitinib in advanced non-smal cel lung cancer (NSCLC). Methods Sixty-six patients with NSCLC received gefitinib as second-line treatment. They were randomly divided into 2 groups, and informed consent forms were signed before grouping. Gefitinib was administrat-ed to the control group, and autologous CIK treatment was added to the observation group. The objective treatment and adverse reactions were evaluated in both groups. Results The objective response rate (ORR) and the disease control rate (DCR) of the observation group were slightly higher than those of the control group, although no statistical dif erences were found between the 2 groups (P > 0.05). The incidences of diarrhea, fatigue, anorexia, oral ulcers, and myelosuppression in the observation group were much lower than those in the control group (P 0.05). Conclusion Autologous CIK in combination with gefitinib is ef ective as second-line treatment for ad-vanced NSCLC, and can significantly reduce adverse reactions and improve the objective ef icacy.

  6. Gefitinib analogue V1801 induces apoptosis of T790M EGFR-harboring lung cancer cells by up-regulation of the BH-3 only protein Noxa.

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    Bo Zhang

    Full Text Available Treatment of non-small cell lung cancer (NSCLC with drugs targeting the epidermal growth factor receptor (EGFR, e.g., gefitinib and erlotinib, will eventually fail because of the development of secondary mutations such as T790M in EGFR. Strategies to overcome this resistance are therefore an urgent need. In this study, we synthesized a dozen of novel gefitinib analogues and evaluated their effects on L858R/T790M-EGFR harboring NSCLC cells, and reported that one of these gefitinib mimetics, N-(2-bromo-5-(trifluoromethyl phenyl-6-methoxy-7-(3-(piperidin-1-ylpropoxyquinazolin-4-amine (hereafter, V1801, triggered apoptosis of the NSCLC cells and overcame gefitinib-resistance in mice inoculated with NCI-H1975 cells. Though V1801 only moderately inhibited EGFR kinase activity, it markedly induced the expression of the BH3-only protein Noxa, and Noxa silencing significantly reduced V1801-induced apoptosis of NCI-H1975 cells. It is showed that V1801 interfered with the expression of the transcription factor c-Myc and the extracellular signal regulated kinase (Erk pathway. V1801 in combination with proteasome inhibitor bortezomib exerted enhanced cytotoxicity in NCI-H1975 cells possibly due to potentiated induction of Noxa expression. These data indicate that gefinitib analogues with weak EGFR inhibitory activity may overcome drug-resistance via activation of BH-3 only pro-apoptotic proteins, and V1801 may have therapeutic potentials for NSCLC.

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

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    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.

  8. 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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    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

  9. The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro

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    Zhao Lu-Jun

    2009-09-01

    Full Text Available Abstract Background Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important reasons why tumor cells resisted to tyrosine kinase inhibitors. Methods To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis. Results The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN. Conclusion These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

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    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.

  12. Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials.

    Science.gov (United States)

    Sohal, D P S; Rice, T W; Rybicki, L A; Rodriguez, C P; Videtic, G M M; Saxton, J P; Murthy, S C; Mason, D P; Phillips, B E; Tubbs, R R; Plesec, T; McNamara, M J; Ives, D I; Bodmann, J W; Adelstein, D J

    2015-01-01

    The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m(2) /day) and cisplatin (20 mg/m(2) /day) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.

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

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    Wenhua Liang

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR

  14. Screening for EGFR Mutations in Patients with Head and Neck Cancer Treated with Gefitinib on a Compassionate-Use Program: A Hellenic Cooperative Oncology Group Study

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    Samuel Murray

    2010-01-01

    Full Text Available Background and Aim. EGFR is commonly expressed in cancers of the head and neck (H and N, and anti-EGFR agents have demonstrated improvements in outcomes (TTP and OS. The aim of this study was to determine EGFR gene status in H and N cancer patients treated with gefitinib and to correlate mutational status with clinico-pathological data and response. Patients and Methods. Patients with histologically confirmed H and N cancer having failed prior treatment for advanced disease entered this compassionate-use-program. Nineteen patients received gefitinib. EGFR expression was assessed by IHC, gene copy number by FISH, and mutation analysis was conducted for EGFR (18-21, KRAS, BRAF (V600E, and HER-2 exon 20. An additional TKI naive cohort of 73 patients was also screened. Results. Mutations were detected in 6/19 patients (3× EGFR, 1× KRAS, and 2× HER2-exon 20. There were no significant differences in TTP or OS for patients with somatic EGFR mutations. No BRAF mutations were detected. Conclusions. The incidence of EGFR mutations in H and N cancer in this study was 5.3%. No statistically relevant correlations between mutation or gene gain and response or survival were observed. Due to the limited number of patients and low incidence of genetic aberrations in the genes analyzed, additional studies are warranted.

  15. Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; TIAN Qing; LIANG Zhi-xin; YANG Zhen; XU Shu-feng; SUN Ji-ping; CHEN Liang-an

    2010-01-01

    Background Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR).Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

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

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    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  18. Synergistic effect of afatinib with su11274 in non-small cell lung cancer cells resistant to gefitinib or erlotinib.

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    Gang Chen

    Full Text Available Epidermal growth factor receptor (EGFR and c-MET receptors are expressed on many non-small cell lung cancer (NSCLC cells. Current single agent therapeutic targeting of a mutant EGFR has a high efficacy in the clinic, but is not curative. Here, we investigated the combination of targeting EGFR and c-MET pathways in NSCLC cells resistant to receptor tyrosine kinase inhibitors (TKIs, using RNA interference and inhibition by TKIs. Different NSCLC cell lines with various genomic characteristics (H358, H1650 and H1975 were transfected with EGFR-specific-siRNA, T790M-specific-siRNA, c-MET siRNA or the combination. Subsequently EGFR TKIs (gefitinib, erlotinib or afatinib or monoclonal antibody cetuximab were combined respectively with the c-MET-specific TKI su11274 in NSCLC cell lines. The cell proliferation, viability, caspase-3/7 activity and apoptotic morphology were monitored by spectrophotometry, fluorimetry and fluorescence microscopy. The combined effect of EGFR TKIs, or cetuximab and su11274, was evaluated using a combination index. The results showed that the cell lines that were relatively resistant to EGFR TKIs, especially the H1975 cell line containing the resistance T790M mutation, were found to be more sensitive to EGFR-specific-siRNA. The combination of EGFR siRNA plus c-MET siRNA enhanced cell growth inhibition, apoptosis induction and inhibition of downstream signaling in EGFR TKI resistant H358, H1650 and H1975 cells, despite the absence of activity of the c-MET siRNA alone. EGFR TKIs or cetuximab plus su11274 were also consistently superior to either agent alone. The strongest biological effect was observed when afatinib, an irreversible pan-HER blocker was combined with su11274, which achieved a synergistic effect in the T790M mutant H1975 cells. In a conclusion, our findings offer preclinical proof of principle for combined inhibition as a promising treatment strategy for NSCLC, especially for patients in whom current EGFR

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

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    Darrell C Bessette

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

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

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    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.

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

    Science.gov (United States)

    2013-01-11

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

  2. The scaffolding protein NHERF1 sensitizes EGFR-dependent tumor growth, motility and invadopodia function to gefitinib treatment in breast cancer cells.

    Science.gov (United States)

    Bellizzi, Antonia; Greco, Maria Raffaella; Rubino, Rosa; Paradiso, Angelo; Forciniti, Stefania; Zeeberg, Katrine; Cardone, Rosa Angela; Reshkin, Stephan Joel

    2015-03-01

    Triple negative breast cancer (TNBC) patients cannot be treated with endocrine therapy or targeted therapies due to lack of related receptors. These patients overexpress the epidermal growth factor receptor (EGFR), but are resistant to tyrosine kinase inhibitors (TKIs) and anti-EGFR therapies. Mechanisms suggested for resistance to TKIs include EGFR independence, mutations and alterations in EGFR and in its downstream signalling pathways. Ligand-induced endocytosis and degradation of EGFR play important roles in the downregulation of the EGFR signal suggesting that its activity could be regulated by targeting its trafficking. Evidence in normal cells showing that the scaffolding protein Na+/H+ exchanger regulatory factor 1 (NHERF1) can associate with EGFR to regulate its trafficking, led us to hypothesize that NHERF1 expression levels could regulate EGFR trafficking and functional expression in TNBC cells and, in this way, modulate its role in progression and response to treatment. We investigated the subcellular localization of NHERF1 and its interaction with EGFR in a metastatic basal like TNBC cell model, MDA-MB‑231, and the role of forced NHERF1 overexpression and/or stimulation with EGF on the sensitivity to EGFR specific TKI treatment with gefitinib. Stimulation with EGF induces an interaction of NHERF1 with EGFR to regulate its localization, degradation and function. NHERF1 overexpression is sufficient to drive its interaction with EGFR in non-stimulated conditions, inhibits EGFR degradation and increases its retention time in the plasma membrane. Importantly, NHERF1 overexpression strongly sensitized the cell to the pharmacological inhibition by gefitinib of EGFR-driven growth, motility and invadopodia-dependent ECM proteolysis. The further determination of how the NHERF1‑EGFR interaction is regulated may improve our understanding of TNBC resistance to the action of existing anticancer drugs.

  3. Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation.

    Science.gov (United States)

    Chang, Cheng-Yi; Shen, Chiung-Chyi; Su, Hong-Lin; Chen, Chun-Jung

    2011-12-01

    Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3 activation, and viability loss. Intriguingly, a nonselective protein phosphatase inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad dephosphorylation. In parallel with the higher basal PKA activity, response of U87 cells to gefitinib treatment was delayed and relatively resistant compared with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87 cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase-9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the inactivation of PKA was shown to play a role in triggering the proapoptotic function of Bad.

  4. 吉非替尼治疗非小细胞肺癌的meta分析%Gefitinib for Non-small Cell Lung Cancer:A meta Analysis

    Institute of Scientific and Technical Information of China (English)

    郭继武; 马彬; 周慧银; 王瑶; 张圆

    2011-01-01

    背景与目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)是恶性程度和死亡率极高的肿瘤,吉非替尼是近年来研发的一种新的分子靶向药物,本文旨在系统评价吉非替尼治疗NSCLC的有效性和安全性.方法 计算机检索Cochrane图书馆(2010年第8期)、PubMed,Embase,CNKI,VIP,中华医学会数字化期刊(截至2010年8月).两名评价者独立评价纳人研究的质量、提取资料并交叉核对,同质研究采用RevMan 5.0软件进行meta 分析.结果 共纳人13个随机对照试验,包括6,207例病例.Meta分析结果显示吉非替尼相比较于安慰剂、多西紫杉醇、顺铂+多西紫杉醇、培美曲赛等治疗方案而言,中位生存时间、1年生存率、完全缓解率、部分缓解率、疾病无进展率等方面未显示出优势.与多西紫杉醇、顺铂+多西紫杉醇相比,吉非替尼可明显增加化疗患者的总有效率(RR=1.41,95%CI:1.10-1.80;RR=1.93,95%CI:1.26-2.94).吉非替尼对比安慰剂、多西紫杉醇能够提高患者的生存质量和总FACT-L改善率(RR=1.42,95%CI:1.16-1.74;RR=1.66,95%CI:139-1.97).吉非替尼的主要不良反应包括皮疹/痊疮、皮肤干操、腹泻.其血液毒性较低.结论 吉非替尼治疗NSCLC有一定的优势,可作为治疗NSCLC的常规药物.%Background and objective Malignant grade and death rate are ,very high for non-small cell lung cancer, and gefitinib is a new molecule target anticancer drug.The aim of this meta analysis is to evaluate the clinical efficacy and safety of gefitinib for non-small cell lung cancer.Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 8, 2010), PubMed (1966-2010.8), EMBASE (1974-2010.8), CNKI (1994-2010.8), VIP (1989-2010.8), and CMD Digital Periodicals (1998-2010.8).Two reviewers independently evaluated the quality of the included studies and extracted the data.Meta-analyses were performed by RevMan 5.0 software

  5. 吉非替尼治疗老年晚期肺癌的临床观察%Clinical observation of gefitinib in the treatment of advanced lung cancer in elderly patients

    Institute of Scientific and Technical Information of China (English)

    王文璋; 王京凯; 王幼黎; 高举; 李娅娜

    2011-01-01

    目的 探讨吉非替尼作为老年晚期肺癌一线治疗方案的可行性.方法 15例经病理学或细胞学证实的老年晚期肺癌初治患者口服吉非替尼250 mg/d,直至患者死亡或肿瘤进展或发生不可耐受的毒副反应,服药前和服药后每月复查胸部CT进行肿瘤评估,分析吉非替尼治疗15例老年晚期肺癌疗效、中位肿瘤进展时间以及对相关症状的控制.结果 客观有效率为(CR+PR)53.3%,疾病控制率为(CR+PR+SD)86.7%,中位肿瘤进展时间(TTP)为5.4个月,中位生存期(MS)为11.1个月.与药物相关的主要不良反应为皮疹(10例).结论 吉非替尼一线治疗老年晚期肺癌显示出良好的耐受性和有效性.%Objective To explore the feasibility of gefitinib as a first-line drug for advanced lung cancer in elderly patients. Methods Fifteen elderly patients with advanced lung cancer confrimed by pathology or cytology were given orally gefitinib 250 mg once a day in initial treatment until death or tumor progression or withdrawal by intolerable reaction. Breast CT scan was performed before and after treatment once a month. The curative effect, disease control rate, median survival time and control of the related symptoms of 15 elderly patients with advanced lung cancer after treated with gefitinib were observed. Results Disease control rate( CR + PR )was 53.3%.Disease control rate( CR + PR + SD ) was 86.7%. The median time to progression ( TTP )was 5.4 months. The median survival time ( MS )was 11.1 months. Skin toxicity was the most common complication( 10 cases ). Conclusion Gefitinib as the first-line drug is effective and tolerable for advanced lung cancer in elderly patients.

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

    Science.gov (United States)

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

    2015-05-22

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

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

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    Chien-Ming Liu

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

  9. Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects.

    Science.gov (United States)

    Bronte, Giuseppe; Rolfo, Christian; Giovannetti, Elisa; Cicero, Giuseppe; Pauwels, Patrick; Passiglia, Francesco; Castiglia, Marta; Rizzo, Sergio; Vullo, Francesca Lo; Fiorentino, Eugenio; Van Meerbeeck, Jan; Russo, Antonio

    2014-02-01

    Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.

  10. 吉非替尼在晚期非小细胞肺癌靶向治疗中的疗效观察%Gefitinib in the Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    袁云

    2012-01-01

    Objective To observe the clinical efficacy and drug-related toxicities of Gefitinib in the treatment of ad vanced non-small cell lung cancel NSCLC ). Methods 16 patients with advanced non-small cell lung cancer diagnosed histolog-ically or cytologically were treated with Gefitinib ( at a dose of 250 mg,per day,orally ) until the disease progression or intolerable toxicities. Results All the 16 patients were evaluable. The overall response rate was 31. 2% , including 0%( 0/16 ) patient with complete response and 31. 2%( 5/16 ) patients with partial response. 43. 8% ( 7/16 ) patients had stable disease and 25.0% ( 4/ 16 ) patients had progressive disease, so the disease control rate is 75. 0%. The median overall survival time ( OS ) was 4. 8 months and the 1-year survival rate was 18. 7% . Drug related adverse reactions included skin rash,diarrhea,xerosiscutis,increas ing level of transaminases, ulcer. 2 patients stopped the treatment due to intolerable diarrhea. Conclusion Gefitinib is effective in the treatment of advanced non-small cell lung cancer obout overall survival, can significantly relieve NSCLC-related symptoms. The toxicities are mild and tolerable. Treatment with Gefitinib could be considered as one of the therapies to advanced non-small cell lung cancer.%目的 探讨吉非替尼(Gefitinib)治疗晚期非小细胞肺癌的有效性及安全性.方法 16例晚期非小细胞肺癌患者采用吉非替尼(250 mg,每天1次,口服)治疗,直至出现疾病进展或发生不可耐受的不良事件.结果 16例均可评价疗效,CR为0%(0/16),PR为31.2%(5/16),SD为43.8%(7/16),PD为25.0%(4/16);客观缓解率(RR)为31.2%,疾病控制率(DCR)为75.0%.中位生存期4.8个月,1年生存率为18.7%.与药物相关的不良反应依次为:皮疹、腹泻、皮肤干燥、转氨酶升高、溃疡.其中有2例患者因腹泻对症治疗不佳而停药.结论 吉非替尼可让既往治疗失败的晚期NSCLC患者生存受益,且不良反应轻,耐受性良好,

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

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

  14. Effect of KRAS exon 2 mutations on antitumor activity of afatinib and gefitinib.

    Science.gov (United States)

    Gamba, Sebastian; Camaj, Peter; Heinemann, Volker; Laubender, Rüdiger P; Wang, Yan; Zhao, Yue; Stintzing, Sebastian; Giessen, Clemens; Boeck, Stefan; Haertl, Christoph; Bruns, Christiane J; Modest, Dominik P

    2015-04-01

    The aim of this study was to investigate the impact of different KRAS mutations on the inhibitory potential of afatinib and gefitinib in SW48 colorectal cancer cells. The influence of afatinib/gefitinib on cell viability and cell cycle was evaluated in isogenic SW48 KRAS wild-type/mutant cells. Protein levels of phosphorylated/total EGFR, HER-2, HER-3, ERK, and AKT were compared between treated/untreated samples using western blotting. The activity of both afatinib and gefitinib was the lowest in KRAS G12C/G12S/G12D and the highest in G13D/G12A mutant subtypes. A 50% decrease in cell viability was achieved at concentrations of 3.0-7.7 μmol/l for afatinib and 5.4-19.5 μmol/l for gefitinib. The effect of both drugs on apoptosis appeared to be stronger than their influence on proliferation and was generally less pronounced in mutant cells than in wild-type cells. The average number of apoptotic cells after treatment with afatinib was 2.6 times as high as the corresponding value following treatment with gefitinib (Pafatinib than by gefitinib (Pafatinib and gefitinib whereas others seem to increase sensitivity to treatment (G13D/G12A) compared with the parental clone (KRAS wild-type). In SW48 colorectal cancer cells, afatinib seems to be more potent than gefitinib because of its superior efficacy in inhibiting both EGFR and HER-2, suppressing signaling along both MEK/ERK and PI3K/AKT pathways to a greater extent.

  15. Gefitinib in the treatment of 41 cases with refractory non-small cell lung cancer%吉非替尼治疗晚期复治性非小细胞肺癌41例

    Institute of Scientific and Technical Information of China (English)

    Jianfang Xu; Caicun Zhou; Aiwu Li

    2009-01-01

    Objective: We observe the curative effect, median survival time, time to progression, quality of life and adverse effect of patients with advanced refractory non-small cell lung cancer (NSCLC) after gefitinib (Iressa) treatment. Methods: Forty-one patients with grade IIIb to IV NSCLC previously treated with two chemotherapy including 85.4% of patients after second line therapy were chosen. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or toxic reaction has become intolerable. The patients were required to receive tumor evaluation before the treatment, one month, two month and every three months after Iressa administration. Results: All of 41 patients were evaluable for thera-peutic effect. Without complete regression being observed, partial response rate (PR), stable disease (SD) and progression of disease (PD) were 43.9% (18/41), 34.1% (14/41) and 22.1% (9/41), respectively. The overall response rate was 43.9% (18/41) and disease control rate (PR + SD) was 78% (32/41). The response rate in male was 42.1%, while it in female was 45.5% (P > 0.05). Twenty-two of them (53.7%, 22/41) were still alive with 10.1 months of MST when the follow-up ended in November 2006. TTP and MST of patients who died was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% of all patients with 13 months of MST of PR patients. The Kamofsky enhanced 20 + 5 after 28 days treatment without 3-4 degree of reactive toxicity. Conclusion: Iressa has significant antitumor activity in advanced NSCLC patients who have previously failed in second or third line chemotherapy. Iressa is effective and safe for patients with poor performance status.

  16. 吉非替尼在晚期非小细胞肺癌维持治疗的作用%Effect of gefitinib on maintenance therapy of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘爱华; 陆京伯; 苏瑾

    2010-01-01

    目的 观察吉非替尼对既往化学治疗有效的晚期(Ⅳ期)非小细胞肺癌维持治疗的疗效和安全性.方法 在15例经病理学确诊的非小细胞肺癌经4~6个周期含铂类方案化疗后取得临床完全缓解和部分缓解患者中,随机选取2例Ⅳ期肺腺癌患者予以吉非替尼维持治疗,250 mg/次,1次/d,口服.结果 2例晚期非小细胞肺癌患者肺部肿瘤进一步缩小,胸腔积液、心包积液消失.病例1放射性核素骨显像示转移病灶放射性浓聚程度明显降低.病例2 MRI显示颅内多发转移病灶稳定.患者生活质量显著提高,KPS评分提高30,症状改善率达100%.不良反应为皮疹和腹泻(Ⅰ级),不需处理.结论 吉非替尼用于既往化疗显效的晚期非小细胞肺癌患者的维持治疗有较好的疗效和安全性.同时可改善患者的相关症状,提高生活质量.%Objective To observe the efficacy and safety of gefitinib on maintenance therapy in patients with advanced (grade Ⅳ ) non-small cell lung cancer after effective chemotherapy. Methods Among 15 patients with non-small cell lung cancer confirmed pathologically who obtained complete response or partial response after 4-6 cycles of chemotherapy, two patients with advanced (grade Ⅵ) adenocarcinoma of lung were randomly selected to be administered gefitinib for maintenance therary, 250 mg,orally once a day. Results In two patients with advanced non-small cell lung cancer, lung tumor reduced further, pleural effusion and pericardial effusion disappeared. Radionuclide bone imaging of the first patient showed that radioactivity level of metastatic lesion reduced. Magnetic resonance imaging of the second patient showed that multiple intracranial metastatic lesions were stable. The quality of life improved significantly,KPS score increased by 30,and the improvement rate of symptom was 100%. The adverse reactions were rash and diarrhea (grade Ⅰ ) ,without treatment. Conclusions Gefitinib is

  17. Metabolomics reveals the formation of aldehydes and iminium in gefitinib metabolism

    Science.gov (United States)

    Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is widely used for the treatment of cancers, particularly non-small cell lung cancer. However, its clinical use is limited by multiple adverse effects associated with GEF, such as liver and lung injuries, sever...

  18. Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation

    Directory of Open Access Journals (Sweden)

    Yi-Ze Zhang

    2016-03-01

    Full Text Available Non-small-cell lung cancer (NSCLC dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M. In this study, we screened a traditional Chinese medicine (TCM compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5′ adenosine monophosphate-activated protein kinase (AMPK. Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

  19. Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation.

    Science.gov (United States)

    Zhang, Yi-Ze; Chen, Xi; Fan, Xing-Xing; He, Jian-Xing; Huang, Jun; Xiao, Da-Kai; Zhou, Yan-Ling; Zheng, Sen-You; Xu, Jia-Hui; Yao, Xiao-Jun; Liu, Liang; Leung, Elaine Lai-Han

    2016-03-18

    Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

  20. Repression of Smad3 by Stat3 and c-Ski/SnoN induces gefitinib resistance in lung adenocarcinoma.

    Science.gov (United States)

    Makino, Yojiro; Yoon, Jeong-Hwan; Bae, Eunjin; Kato, Mitsuyasu; Miyazawa, Keiji; Ohira, Tatsuo; Ikeda, Norihiko; Kuroda, Masahiko; Mamura, Mizuko

    2017-03-04

    Cancer-associated inflammation develops resistance to the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancers (NSCLCs) harboring oncogenic EGFR mutations. Stat3-mediated interleukin (IL)-6 signaling and Smad-mediated transforming growth factor-β (TGF-β) signaling pathways play crucial regulatory roles in cancer-associated inflammation. However, mechanisms how these pathways regulate sensitivity and resistance to EGFR-TKI in NSCLCs remain largely undetermined. Here we show that signal transducer and activator of transcription (Stat)3 represses Smad3 in synergy with the potent negative regulators of TGF-β signaling, c-Ski and SnoN, whereby renders gefitinib-sensitive HCC827 cells resistant. We found that IL-6 signaling via phosphorylated Stat3 induced gefitinib resistance as repressing transcription of Smad3, whereas TGF-β enhanced gefitinib sensitivity as activating transcription of Smad3 in HCC827 cells with gefitinib-sensitizing EGFR mutation. Promoter analyses showed that Stat3 synergized with c-Ski/SnoN to repress Smad2/3/4-induced transcription of the Smad3 gene. Smad3 was found to be an apoptosis inducer, which upregulated pro-apoptotic genes such as caspase-3 and downregulated anti-apoptotic genes such as Bcl-2. Our results suggest that derepression of Smad3 can be a therapeutic strategy to prevent gefitinib-resistance in NSCLCs with gefitinib-sensitizing EGFR mutation.

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

    Science.gov (United States)

    Galetti, Maricla; Petronini, Pier Giorgio; Fumarola, Claudia; Cretella, Daniele; La Monica, Silvia; Bonelli, Mara; Cavazzoni, Andrea; Saccani, Francesca; Caffarra, Cristina; Andreoli, Roberta; Mutti, Antonio; Tiseo, Marcello; Ardizzoni, Andrea; Alfieri, Roberta R.

    2015-01-01

    Background 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. Aim 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. Methods and Results 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. Conclusions 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. PMID:26536031

  2. Gefitinib

    Science.gov (United States)

    ... proton pump inhibitor medication for indigestion, heartburn, or ulcers such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (AcipHex), ...

  3. 吉非替尼治疗伴有EGFR基因检测的非小细胞肺癌的文献综合分析%Meta Analysis of Gefitinib for the Treatment of Non-small Cell Lung Cancer with the Expression of EGFR Gene

    Institute of Scientific and Technical Information of China (English)

    李倩琴; 李恩泽

    2012-01-01

    [Objectivel To understand the efficacy of gefitinib for the treatment of non-small cell lung cancer (NSCLC) and the correlation between biological characteristics and the efficacy. [Methods] Six prospective clinical trails of NSCLC patients with the expression of EGFR gene receiving gefitinib therapy which were collected from Pubmed and ScienceDirect network site were analyzed. [Results]The characteristics, EGFR gene mutation, efficacy and side effects of patients treated with gefitinib were listed and compared. CR, PR, SD, PD, RR, DCR, mean non-progressive survival time and mean total survival time of patients with EGFR mutation were better than those of total patients. The efficacy of patients with EGFR mutation was better than total patients. The results suggested that gefitinib for the treatment of patients with EGFR mutation had better efficacy. The NSCLC patients with EGFR mutation were the superior population of gefitinib therapy. [Conclusion] Asian, women and non-smokers are the predominant population of gefitinib. Gefitinib has better efficacy than platinum-based chemotherapy. The efficacy of gefitinib for the treatment of NSCLC patients with EGFR mutation is better than those without EGFR mutation.%[目的]了解吉非替尼治疗非小细胞肺癌肺癌的疗效及生物学特性与治疗疗效的相关性.[方法]在Pubmed和Sciencedirect网站收集了6个伴有EGFR基因检测的非小细胞肺癌使用吉非替尼治疗的前瞻性临床试验进行分析.[结果]分别对吉非替尼治疗的患者特征、患者EGFR基因突变、疗效及不良反应的数据进行列表并对比分析.有EGFR基因突变患者的CR、PR、SD、PD、RR、DCR、中位无进展生存期、中位总生存期的各项结果均优于总体患者的结果,有EGFR基因突变患者疗效情况比总体患者疗效情况好,提示吉非替尼对有EGFR基因突变患者治疗效果更佳,是吉非替尼治疗NSCLC的优势人群.[结论]吉非替尼的优势人群为亚

  4. Effects of polymorphisms in CYP2D6 and ABC transporters and side effects induced by gefitinib on the pharmacokinetics of the gefitinib metabolite, O-desmethyl gefitinib.

    Science.gov (United States)

    Kobayashi, Hiroyuki; Sato, Kazuhiro; Niioka, Takenori; Takeda, Masahide; Okuda, Yuji; Asano, Mariko; Ito, Hiroshi; Miura, Masatomo

    2016-06-01

    We investigated the effects of polymorphisms in CYP2D6, ABCB1, and ABCG2 and the side effects induced by gefitinib on the pharmacokinetics of O-desmethyl gefitinib, the active metabolite of gefitinib. On day 14 after beginning therapy with gefitinib, plasma concentrations of gefitinib and O-desmethyl gefitinib were measured. Patients were grouped into three groups according to their combination of CYP2D6 alleles: homozygous extensive metabolisers (EMs; *1/*1, *1/*2, and *2/*2; n = 13), heterozygous EMs (*1/*5, *2/*5, *1/*10, and *2/*10; n = 18), and intermediate metabolisers (IMs; *5/*10 and *10/*10; n = 5). The median AUC0-24 of O-desmethyl gefitinib in CYP2D6 IMs was 1460 ng h/mL, whereas that in homozygous EMs was 12,523 ng h/mL (P = 0.021 in univariate analysis). The median AUC ratio of O-desmethyl gefitinib to gefitinib differed among homozygous EMs, heterozygous EMs, and IMs at a ratio of 1.41:0.86:0.24 (P = 0.030). On the other hand, there were no significant differences in the AUC0-24 of O-desmethyl gefitinib between ABCB1 and ABCG2 genotypes. In a multivariate analysis, CYP2D6 homozygous EMs (P = 0.012) were predictive for a higher AUC0-24 of O-desmethyl gefitinib. The side effects of diarrhoea, skin rash, and hepatotoxicity induced by gefitinib were unrelated to the AUC0-24 of O-desmethyl gefitinib. CYP2D6 polymorphisms were associated with the formation of O-desmethyl gefitinib from gefitinib. In CYP2D6 homozygous EMs, the plasma concentrations of O-desmethyl gefitinib were higher over 24 h after taking gefitinib than those of the parent compound; however, side effects induced by gefitinib were unrelated to O-desmethyl gefitinib exposure.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-01

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

  6. 吉非替尼与普通化疗一线治疗晚期非小细胞肺癌的比较研究%A Comparative Study of Gefitinib and Traditional Chemotherapy in First-line Treatment of Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    孙薇薇; 陈文

    2014-01-01

    Objective: Based on published literatures, the study aimed to compare the efficacy, safety and cost-effectiveness of gefitinib with traditional chemotherapy in first-line treatment of EGFR-mutation advanced non-small cell lung cancer (NSCLC). Methods:A systematic review method was performed to search and retrieve the evidence from various databases including Pubmed, Medline, CNKI, etc. We collected English and Chinese studies during last decade on comparison of gefitinib with traditional chemotherapy in first-line treatment of NSCLC. Results:With inclusion and exclusion criteria, there were 5 clinical studies and 2 cost-effectiveness studies finally recruited for the analysis. Clinical results showed that progression-free survival and objective response rate favored gefitinib in the first-line treatment of EGFR-mutation NSCLC. Also gefitinib was proved to be superior to traditional chemotherapy in safety and improvement in quality of life. Two cost effectiveness studies revealed that from the perspective of UK NHS and Singapore society, gefitinib was cost effective compared with traditional chemotherapy. Conclusions:Gefitinib can be considered as a standard option in the first-line treatment of EGFR-mutation NSCLC. More evidences on cost and cost effectiveness of gefitinib for EGFR-mutation NSCLC patients in China are still needed to support clinical usage and local public decision making on health insurance benefits update in China.%目的:通过文献系统综述,对吉非替尼和普通化疗一线治疗EGFR突变阳性的晚期非小细胞肺癌的临床疗效、安全性、生命质量和成本-效果进行比较研究。方法:在Pubmed、Medline、中国期刊全文数据库(CNKI)等检索近10年发表的比较吉非替尼和化疗一线治疗晚期NSCLC的文献。结果:纳入临床研究5个,显示吉非替尼在改善无进展生存期和客观缓解率上好于化疗,安全性和生活质量的改善好于化疗。2个成本-效果研究

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  8. 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.)

  9. 吉非替尼对非小细胞肺癌细胞株H358增殖的影响及其作用机制%Effects and mechanism of gefitinib on the proliferation of non-small cell lung cancer cell line H358

    Institute of Scientific and Technical Information of China (English)

    张雷; 李宝平; 吴艳娟; 任宏伟; 王轩

    2013-01-01

    目的:观察吉非替尼(gefitinib)对非小细胞肺癌(NSCLC)细胞株H358增殖的影响,并对其分子机制进行探讨。方法体外培养人NSCLC细胞株 H358,随机分为正常培养对照组和1μmol/L吉非替尼处理组,培养1、3、5 d后,应用M TS法对2组细胞增殖速率进行分析;分别提取胞质、胞核蛋白,蛋白印迹法检测表皮生长因子受体(EGFR)的亚细胞定位变化情况;另外,对细胞中磷酸化-Akt(p-Akt)的表达进行检测,分析其对磷脂酰肌醇-3激酶(PI3K)/Akt信号通路的影响。结果M TS结果表明,1μmol/L吉非替尼能显著抑制 H358的增殖(P<0.01),并具有时间依赖性。蛋白印迹法检测结果显示,吉非替尼能够改变EGFR的亚细胞定位,减少其在胞核中的表达,此外,吉非替尼处理后 H358细胞内p-Akt的蛋白表达受到抑制。结论吉非替尼能够显著抑制H358细胞的增殖,减少EGFR在细胞核中的表达,并抑制PI3K/Akt信号通路,这可能是其抗NSCLC的重要细胞及分子机制。%Objective To investigate the effects of gefitinib on the proliferation of non-small cell lung canc-er (NSCLC) cell line H358 ,and to explore the underlying molecular mechanism .Methods Human NSCLC H358 cells were cultured in vitro .Cells were divided randomly into the control group and gefitinib treated group ,after cultured for 1 ,3 ,5 days .The proliferation of H358 was investigated by M TS assay ,and the Western blotting was applied to investigate the sub-cellular location of epidermal growth factor receptor (EGFR) by extracting the protein of cytoplasm and nucleus separately ,and the protein expression of phospho-Akt ,a component of the PI3K/Akt signaling pathway .Results M TS assay results showed that gefitinib inhibited the proliferation of H 358 sig-nificantly (P<0.01) in a time dependent manner .Western blotting results showed that the sub-cellular location of EGFR was affected by

  10. 整合素β1信号通路参与非小细胞肺癌吉非替尼获得性耐药%Integrin β1 participates in acquired resistance to gefitinib in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    邓沁芳; 徐建芳; 粟波; 赵印敏; 周彩存

    2012-01-01

    目的 探讨整合素β1及其下游信号转导通路在非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂(EGFRTKI)吉非替尼获得性耐药中的作用.方法 以人肺腺癌细胞株PC-9和吉非替尼耐药株pC-9/G作为研究对象,免疫印迹分析检测整合素β1、Akt、磷酸化Akt蛋白的表达;用MTT法检测吉非替尼和(或)磷脂酰肌醇3激酶(PI3K)抑制剂LY294002、细胞外调节蛋白激酶(ERK)抑制剂PD98059对细胞增殖的影响;用Annexin V/PI试剂盒和TUNEL试剂盒检测细胞凋亡.结果 吉非替尼耐药株PC-9/G高表达整合素β1,RNA T扰抑制整合素β1表达能够抑制PC-9/G细胞的生长和促进凋亡.PC-9/G细胞中吉非替尼对Akt磷酸化的抑制作用弱于PC-9细胞,RNA干扰抑制整合素β1表达后Akt的磷酸化水平降低.ERK抑制剂PD98059不能恢复PC-9/G细胞对吉非替尼的敏感性,PI3K抑制剂LY294002能恢复PC-9/G细胞对吉非替尼的敏感性.结论 整合素β1过表达可以通过PI3K途径激活下游信号分子,这可能是一种重要的EGFR TKI耐药机制.%Objective To explore the role of integrin β1 and relevant signaling pathway in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib in non-small cell lung cancer (NSCLC). Methods Human lung adenocarcinoma cell line PC-9 and gefitinib-resistant PC-9/G cell lines were used in the present study. Western blotting analysis was used to examine the expression of integrin β1 , Akt and phospho-Akt protein. The inhibitory effects of gefitinib and/or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and extracellular regulated protein kinases (ERK) inhibitor PD98059 on cellular proliferation were tested by MTT assay. Cell apoptosis was analyzed by Annexin V/PI and TUNEL method. Results Overexpression of integrin p, was observed in PC-9/G cell line. Silencing integrin β1 by RNAi method inhibited the proliferation and promoted apoptosis of PC-9/G cells

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-10

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

  14. Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining

    Science.gov (United States)

    Verma, Nidhi; Rai, Amit Kumar; Kaushik, Vibha; Brünnert, Daniela; Chahar, Kirti Raj; Pandey, Janmejay; Goyal, Pankaj

    2016-01-01

    Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug. PMID:27653775

  15. Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining.

    Science.gov (United States)

    Verma, Nidhi; Rai, Amit Kumar; Kaushik, Vibha; Brünnert, Daniela; Chahar, Kirti Raj; Pandey, Janmejay; Goyal, Pankaj

    2016-09-22

    Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug.

  16. Achievement of Cure with Gefitinib in Advanced Lung Adenocarcinoma Harboring an Activating EGFR Mutation: A Case Report

    Directory of Open Access Journals (Sweden)

    Taiji Kuwata

    2016-10-01

    Full Text Available Tyrosine kinase inhibitors (TKIs of the epidermal growth factor receptor (EGFR may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

  17. Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib

    NARCIS (Netherlands)

    Janjigian, Y Y; Groen, H J; Horn, L; Smit, E F; Fu, Y; Wang, F; Shahidi, M; Denis, L J; Pao, W; Miller, V A

    2011-01-01

    7525^ Background: Despite initial responses to reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, (erlotinib or gefitinib), all non-small cell lung cancer (NSCLC) patients with EGFR-sensitizing mutations experience disease progression. This "acquired resistance" (AR) is a

  18. Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib

    NARCIS (Netherlands)

    Janjigian, Y. Y.; Groen, H. J.; Horn, L.; Smit, E. F.; Fu, Y.; Wang, F.; Shahidi, M.; Denis, L. J.; Pao, W.; Miller, V. A.

    2011-01-01

    Background: Despite initial responses to reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, (erlotinib or gefitinib), all non-small cell lung cancer (NSCLC) patients with EGFR-sensitizing mutations experience disease progression. This “acquired resistance” (AR) is associa

  19. Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib

    Directory of Open Access Journals (Sweden)

    Yuan Ying

    2012-11-01

    Full Text Available Abstract About 20% to 40% of patients with non-small cell lung cancer (NSCLC will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT, some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS were obtained. Double dosage of gefitinib (500 mg per day together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.

  20. Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction

    Directory of Open Access Journals (Sweden)

    Wang Wen-Ping

    2012-01-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib. Methods From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced. Results In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977. No genetic alteration was found in exons 18, 19 or 21. Conclusions Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.

  1. [Prospective study of biotin treatment in patients with erythema due to gefitinib or erlotinib].

    Science.gov (United States)

    Ogawa, Yoshikazu; Kiba, Takayoshi; Nakano, Kikuo; Fujiwara, Keiichi; Taniguchi, Hitoshi; Hosokawa, Atsuko; Nakashima, Toshihisa; Kimoto, Shizue; Kajiume, Sayoko; Okada, Yuuko; Ichiba, Yasunori

    2014-04-01

    Gefitinib anderlotinib, which are epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs), have been usedfor the treatment of inoperable andrecurrent non-small cell lung cancer(NSCLC)patients. These drugs are known to cause a skin rash, one of the major side effects, at a high frequency. Biotin is a water-soluble vitamin, andit belongs to the vitamin B family. It is well known that biotin deficiency increases the risk of skin dermatitis. We administered biotin to four patients with skin rash, all of whom were treatedwith either gefitinib or erlotinib andwere unable to be treatedby a steroid ointment alone. In all patients, administration of biotin reduced the skin rash. Surprisingly, in 2 patients in whom EGFR-TKI therapy was discontinued because of the skin rash, the administration of biotin allowed for long-term gefitinib or erlotinib treatment. Biotin may be considereduseful for the treatment of skin rash causedby EGFR-TKIs. Further trials may be needed to confirm the value of biotin in this setting.

  2. European randomized lung cancer screening trials: Post NLST

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. Gefitinib resistance in HCC mahlavu cells: upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation.

    Science.gov (United States)

    Bodzin, Adam S; Wei, Zhengyu; Hurtt, Reginald; Gu, Tina; Doria, Cataldo

    2012-07-01

    Hepatocellular carcinoma (HCC) is the major form of primary liver cancer which accounts for more than half million deaths annually worldwide. While the incidence of HCC is still on the rise, options of treatment are limited and the overall survival rate is poor. The acquisition of cancer drug resistance remains one of the key hurdles to successful treatment. Clearly, a thorough understanding of the underlying mechanisms is needed for new strategies to design novel treatments and/or to improve the current therapies. In the present study, we examined the expression of cancer stem cell (CSC) marker CD133, the activation of insulin-like growth factor 1 receptor (IGF-1R) signaling, and the nuclear translocation of IGF-1R in HCC Mahlavu cells under the treatment of gefitinib, a cancer drug that inhibits epidermal growth factor receptor (EGFR) pathway. Our results demonstrated that Mahlavu cells exhibited strong gefitinib resistance and the CD133 expression level was dramatically increased (from 3.88% to 32%) after drug treatment. In addition, the gefitinib treated cells displayed increased levels of phosphorylation in IGF-1R and Akt, indicating the intensified activation of this cancer-associated signaling pathway. Moreover, we revealed that IGF-1R underwent nuclear translocation in gefitinib treated cells using confocal microscopy. The IGF-1R nuclear translocation was enhanced under gefitinib treatment and appeared in a dose-dependent manner. Our findings suggest that increased IGF-1R nuclear translocation after gefitinib treatment may contribute to the drug resistance and IGF1-R activation, which might also associate with the upregulation of CD133 expression.

  4. CLINICAL OBSERVATION OF GEFITINIB IN TREATMENT OF PATIENTS WITH ADVANCED ADENOCARCINOMA OF LUNG CANCER%吉非替尼治疗晚期肺腺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    江波; 赵金奇; 何文杰

    2011-01-01

    [Objective] To analyze the efficacy, median survival time, media progression-free survival and control of the related symptoms of SO advanced lung adenocarcinoma caaes treated with Gefitinib. [Methods] A total of 50 patients with advanced lung adenocarcinoma of stage IE B or IV confirmed by pathology or cytology took Gefitinib 2S0mg orally once a day, until death or tumor progression or withdrawal by intolerable reaction. CT scan was performed before treatment and after treatment once a month. [Results] Objective response rate was 24%, disease control rate was 76%, and symptom improving rate was 70%. Significant difference was found in the efficacy of gender and smoking history (P 0.05). Median progression-free survival time was 7.5 months. Median survival time was 16.8 months. Skin rash and diarrha were the most common complication. [Conclusion] Gefitinib is better choice for the patients with advanced lung adenocarcinoma.%[目的]分析吉非替尼治疗50例晚期肺腺癌的疗效、中位生存期、中位无进展生存期及对相关症状的控制.[方法]50例经病理学或细胞学证实的ⅢB期或Ⅳ期肺腺癌患者,口服吉非替尼250 mg/d,直至患者死亡或肿瘤进展或发生不可耐受的不良反应,服药前或服药后每月复查CT进行疗效评价.[结果]客观缓解率为24%,疾病控制率为76%,症状改善率为70%,性别及吸烟两亚组之间疗效对比有统计学差异(P<0.05);年龄、分期、PS评分及既往治疗等各亚组之间疗效对比均无统计学差异(P>0.05).中位无进展生存期7.5个月,中位生存期16.8个月,最常见的不良反应为皮疹和腹泻.[结论]吉非替尼是晚期肺腺癌治疗较好的选择.

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

    Directory of Open Access Journals (Sweden)

    William Pao

    2005-03-01

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

  6. Therapeutic effect of imatinib on advanced non-small cell lung cancer Shenlingbaizhu granule combined with gefitinib%参苓白术颗粒联合吉非替尼对晚期非小细胞肺癌的治疗作用

    Institute of Scientific and Technical Information of China (English)

    王永海; 邢建群; 寇丽春

    2015-01-01

    Objective Observation of Shenling Baizhu granule combined with gefitinib in advanced non small cell lung can-cer (NSCLC ) treatment effect .Methods Select diagnosed by pathology or cytology of 40 cases of NSCLC patients ,were ran-domly divided into treatment group and control group ,the patients in the treatment group received oral Shenling Baizhu parti-cles ,6 g/3 times/d ,gefitinib 250 mg/d orally;the control group only received gefitinib 250 mg/d orally ;the two groups were treated for 21 d as 1 chemotherapy cycle ,at least 3 cycles of treatment .A comparison of the short-term efficacy ,quality of life ,the two groups of patients with clinical symptoms improvement and the changes of T cell subset .Results No signifi-cance between the two groups of curative effect in the near future ( P>0 .05 );the treatment group after treatment ,KPS score ,quality of life to improve the clinical curative effect of TCM syndrome was significantly higher than that in control group ( P<0 .05 ) .The treatment group CD4 after treatment than before treatment ( P<0 .05 ) increased .Conclusion Large headed Atractylodes granule combined with gefitinib can significantly improve the life quality of patients with advanced NSCLC ,regulate immune function .%目的:观察参苓白术颗粒联合吉非替尼对晚期非小细胞肺癌(NSCLC )的治疗效果。方法选取经病理组织学或细胞学确诊为NSCLC患者40例,随机分为治疗组及对照组。治疗组患者给予参苓白术颗粒口服,6 g/次,3次/d ,吉非替尼250 mg/d口服;对照组仅给予吉非替尼250 mg/d口服。2组均连续治疗21 d为1个化疗周期,至少治疗3个周期,对比2组患者近期疗效、生活质量、中医症状改善及T细胞亚群变化。结果2组近期疗效比较无统计学意义(P>0.05);治疗组治疗后生活质量KPS评分改善,中医证候临床疗效显著高于对照组( P<0.05),治疗组治疗后CD4较治疗前升高( P<0

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

    Directory of Open Access Journals (Sweden)

    Åman Pierre

    2008-01-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Xinyu ZHANG

    2012-03-01

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

  10. 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.

  11. European Randomized Lung Cancer Screening Trials : Post NLST

    NARCIS (Netherlands)

    Field, John K.; van Klaveren, Rob; Pedersen, Jesper H.; Pastorino, Ugo; Paci, Eugino; Becker, Nikolauss; Infante, Maurizo; Oudkerk, Matthijs; de Koning, Harry J.

    2013-01-01

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

  12. The treatment of Gefitinib and Docetaxel plus Cisplatin for Advanced Non-small Cell Lung Cancer%吉非替尼和多西他赛+顺铂方案治疗晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    李新权; 吕靖; 刘婷

    2013-01-01

    目的:观察吉非替尼和多西他赛+顺铂方案治疗晚期非小细胞肺癌(NSCLC)的近期疗效、生活质量和不良反应。方法:92例晚期NSCLC患者,试验组46例:吉非替尼,250 mg/d ,口服,每个治疗周期为1个月;对照组46例:多西他赛+顺铂方案,多西他赛75 mg/m2,第1天,顺铂75 mg/m2,第2天,每3周为1个周期,两组均两周期后评价近期疗效、生活质量及不良反应。结果:两组总有效率试验组32.6%,对照组21.7%, P>0.05,差异无显著性。试验组疾病控制率试验组71.7%,对照组50.0%, P0.05, there was no significant difference. The test group for disease control rate of the test group 71.7%, control group 50%, P<0.05,there are significant difference. The test group quality of life than that in the control group, P< 0.05. The main toxicity test group was rash and diarrhea, the main toxicity of control group were myelosup pression and gastrointestinal reaction, P<0.05. Conclusion:single agent gefitinib than docetaxel+cisplatin and can be used in the treatment of advanced non smal celllung cancer, but gefitinib disease control rate is high, the quality of life improvement rate higher, adverse reactions are mild, wel tolerated.

  13. 吉非替尼和NS398对前列腺癌PC-3M细胞增殖和侵袭力影响的研究%Effects of gefitinib and NS-398 on the proliferation and invasion ability of prostate cancer cell line ;PC-3 in vitro

    Institute of Scientific and Technical Information of China (English)

    朱佳庚; 吴宏飞; 林建中

    2014-01-01

    Objective To observe the effects and possible mechanism of epidermal growth factor receptor specific inhibitor gefitinib and cyclooxygenase-2 specific inhibitor NS-398 on the proliferation and invasion ability of prostate cancer cell line PC-3M in vitro. Methods Cell proliferation was assayed by using MTT method.The invasion ability was examined by Transwell assay. The mRNA and protein expression of MMP-9 and VEGF was detected by quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR), and Western blotting respectively. Results MTT analyses revealed that gefitinib and NS-398 combination markedly induced decrease in cell viability compared to either drug(P<0.05). Additionally, the two drugs combination showed a greater suppression in the invasion ability (P<0.01). Also, we found that the combination induced more profound decrease in the expression level of MMP-9 and VEGF mRNA and protein (P<0.01). Conclusions The results suggest that gefitinib and NS-398 combination can significantly suppress PC-3M cells proliferation and invasion ability. VEGF and MMP-9 gene down-regulation may be involved in this progress.%目的:应用表皮生长因子受体(EGFR)特异性阻断剂吉非替尼(Gefitinib)和环氧化酶2(COX-2)特异性阻断剂NS398单独或联合作用于前列腺癌PC-3M细胞,观察对细胞增殖和侵袭能力的影响及可能机制研究。方法采用四甲基偶氮唑蓝法(MTT)和 Transwell 检测Gefitinib和NS398应用对细胞增殖和侵袭能力的影响,应用实时荧光定量聚合酶链反应(qRT-PCR)和Western blot法检测药物应用前后基质金属蛋白酶9(MMP-9)、表皮生长因子(VEGF)基因和蛋白表达水平的变化。结果 MTT结果显示Gefitinib或NS398都可抑制PC-3M细胞增殖(P<0.05),两者联合应用作用更明显(P<0.01),Transwell结果表明两种阻断剂都能在一定程度上抑制细胞侵袭能力(P<0.05)

  14. Clinical observation on treatment with gefitinib in advanced non-small cell lung cancer patients failed to previous chemotherapy%吉非替尼治疗化疗失败的晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    马锐

    2011-01-01

    目的:评价吉非替尼治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应.方法:对68例化疗失败的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250mg,qd,口服,至病情进展或出现不可耐受的不良反应.结果:68例患者中,CR 1例,PR 20例,SD 23例,PD 24例.有效率30.88%(21/68),疾病控制率为64.71%(44/68);全组中位疾病进展时间(TTP)为5.2个月,中位生存时间为9.3个月,1年生存率为52.94%(36/68).与药物相关的不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,皮疹发生率为26.47% (18/68),腹泻发生率为19.12%(13/68),多在用药后1周内出现,症状轻不需特殊处理.1例出现Ⅰ度转氨酶升高.结论:吉非替尼治疗化疗失败的晚期非小细胞肺癌安全有效,不良反应轻微,患者耐受性和依从性良好.%Objective:To evaluate the efficacy and toxicity of gefitinib in treatment of patients with non - small cell lung cancer ( NSCLC )who failed to previous chemotherapy. Methods: Total of 68 failed to previous chemotherapy patients with advanced NSCLC confirmed by pathology or cytology were treated with oral gefitinib 250 mg/d until disease progression, or intolerated toxicity. Results: Of 68 patients, one patient achieved complete remission ,20 patients achieved partial response, 23 achieved stable disease and 24 had progressive disease. Response rate was 30.88%( 21/68 ) disease control rate 64.71%( 44/68 )median time to progression 5.2 months, median overall survival 9.3 months, 1 -year survival rate 52.94%( 36/68 ). Drug - related toxicity was mainly mild ( 1 or 2 grade )skin reactions and diarrhea. skin reactions occurred in 26.47% of patients ( 18/68 ), diarrhea occurred in 19.12%of patients ( 13/68 ), symptoms more appeared in a week after administration, and could relieve without any special treatment, 1 patient happened mild transaminase elevation. Conclusion: Gefitinib is effiectire and safe to advanced NSCLC failed to previous

  15. Isorhamnetin Suppresses the Growth of Gefitinib Resistant Human Lung Cancer PC9 Cells%异鼠李素抑制耐吉非替尼人肺癌细胞PC9增殖的研究

    Institute of Scientific and Technical Information of China (English)

    李川; 杨熹; 胡俊波; 廖家智

    2012-01-01

    Objective To investigate the role of isorhamnetin on the growth of PC9-IR cells. Methods The gefitinib-resistant PC9(PC9-1R) cells were generated by consistently culturing the PC9 cells with 10% FBS/DMEM contained 0.5 μmol·L-1 gefitinib. Then, the PC9-1R cells were treated with isorhamnetin at different concentrations. The proliferation was detected by MTT assay after 24,48 and 72 h, respectively, with PBMNCs as control. Western blot assay was used to detect the change of growth signal pathway. Additionally, clonal assay was performed to analyze the clone formation ability of PC9-IR with or without isorhamnetin. Results Isorhamnetin inhibitted the growth of PC9-1R. The IC50 at the three time points were 212 μmol·L-1 (24 h) ,98 μmol·L-1(48 h) ,64 μmol·L-1(72 h) ,and PBMNCs was 204 μmol·L-1(72 h). It was showed thai the phosph-Akt was suppressed and the clonal formation ability of PC9-IR was lowered by isorhamnetin. Conclusion Isorhmantin could inhibit the growth of PC9-IR cells through suppressing the phosphorylation of Akt.%目的 检测异鼠李素对耐吉非替尼的人肺癌细胞PC9增殖的影响.方法 通过持续在人肺癌细胞系PC9的培养条件中加入吉非替尼培养直到PC9细胞出现耐药情况,即得到耐药细胞株(PC9-1R).再将PC9-IR用不同浓度的异鼠李素处理,分别在24,48和72 h后用噻唑蓝(MTT)法检测细胞的生长情况,以正常人外周血单个核细胞(PBMNCs)作为对照组.同时采用蛋白质印迹法检测药物作用之后信号通路的变化,再用克隆分析检测isorhamentin对细胞克隆形成的影响.结果 MTT证实异鼠李素对PC9-IR的生长有明显的抑制作用,24,48,72 h的半数抑制浓度(IC50)分别为212,98,64 μmol·L-1,而对PBMNCs72 h的IC50为204 μmol·L-1,蛋白质印迹法证实isorhamnetin可以抑制Akt473位的磷酸化,克隆分析证实40 μmol·L-1异鼠李素可明显抑制PC9-IR的克隆形成.结论 异鼠李素对耐药的人肺癌细胞系(PC9-IR)的生

  16. Genome-wide profiling of micro-RNA expression in gefitinib-resistant human lung adenocarcinoma using microarray for the identification of miR-149-5p modulation.

    Science.gov (United States)

    Hu, Yong; Qin, Xiaobing; Yan, Dali; Cao, Haixia; Zhou, Leilei; Fan, Fan; Zang, Jialan; Ni, Jie; Xu, Xiaoyue; Sha, Huanhuan; Liu, Siwen; Yu, Shaorong; Wu, Jianzhong; Ma, Rong; Feng, Jifeng

    2017-03-01

    To understand the mechanism involved in gefitinib resistance, we established gefitinib-resistant human HCC827/GR-8-1 cell line from the parental HCC827 cell line. We compared the micro-RNA expression profiles of the HCC827 cells HCC827/GR-8-1 using Agilent micro-RNA microarrays. The micro-RNAs, such as the miR-149-5p, were up- or downregulated and associated with acquired gefitinib resistance. Quantitative real-time polymerase chain reaction was then performed to verify the expression patterns of different micro-RNAs. The result showed that miR-149-5p was upregulated in the HCC827/GR-8-1 cell line. To investigate the biological function of miR-149-5p in non-small cell lung cancer cells acquired gefitinib resistance, we examined cell proliferation using a cell counting kit-8 assay. Cell viability was evaluated after the miR-149-5p mimics, inhibitors, and negative control were separately transfected into the non-small cell lung cancer cells. The results showed that the non-small cell lung cancer cells transfected with miR-149-5p mimics exhibited reduced cell motility. The drug-sensitivity assay results revealed that the overexpression of miR-149-5p effectively evaluates the half maximal inhibitory concentration values of the cell in response to gefitinib, and the downregulation of miR-149-5p can attenuate the half maximal inhibitory concentration values of the cell lines in response to gefitinib. Furthermore, the levels of miR-149-5p in the HCC827 and HCC827/GR-8-1 cells were inversely correlated with caspase-3 expression. In conclusion, this study revealed that miR-149-5p is upregulated in the HCC827/GR-8-1 cells and involved in the acquired gefitinib resistance.

  17. 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

  18. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer

    DEFF Research Database (Denmark)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine;

    2016-01-01

    BACKGROUND AND AIMS: 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....... METHODS: 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 (d...

  19. European randomized lung cancer screening trials: Post NLST.

    Science.gov (United States)

    Field, John K; van Klaveren, Rob; Pedersen, Jesper H; Pastorino, Ugo; Paci, Eugino; Becker, Nikolauss; Infante, Maurizo; Oudkerk, Matthijs; de Koning, Harry J

    2013-10-01

    Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects of their trials at August 2010, which included 32,000 people, inclusion of UKLS pilot trial will reach 36,000. An interim analysis is planned, but the final mortality data testing is scheduled for 2015.

  20. Enhancing Anticancer Effect of Gefitinib across the Blood-Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80.

    Science.gov (United States)

    Lin, Kuan-Hung; Hong, Shu-Ting; Wang, Hsiang-Tsui; Lo, Yu-Li; Lin, Anya Maan-Yuh; Yang, James Chih-Hsin

    2016-11-29

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd.3 cells. Gefitinib was encapsulated in small unilamellar liposomes modified with glutathione (GSH) and Tween 80 (SUV-G+T; one ligand plus one surfactant) or RF (SUV-RF; one α-helical cell-penetrating peptide). GSH, Tween 80, and RF were tested by the sulforhodamine B (SRB) assay to find their non-cytotoxic concentrations on bEnd.3 cells. The enhancement on gefitinib across the BBB was evaluated by cytotoxicity assay on human lung adenocarcinoma PC9 cells under the bEnd.3 cells grown on the transwell inserts. Our findings showed that gefitinib incorporated in SUV-G+T or SUV-RF across the bEnd.3 cells significantly reduced the viability of PC9 cells more than that of free gefitinib. Furthermore, SUV-RF showed no cytotoxicity on bEnd.3 cells and did not affect the transendothelial electrical resistance (TEER) and transendothelial permeability of sodium fluorescein across the BBB model. Moreover, flow cytometry and confocal laser scanning microscopy were employed to evaluate the endocytosis pathways of SUV-RF. The results indicated that the uptake into bEnd.3 cells was mainly through adsorptive-mediated mechanism via electrostatic interaction and partially through clathrin-mediated endocytosis. In conclusion, cell penetrating peptide-conjugated SUV-RF shed light on improving drug transport across the BBB via modulating the transcytosis pathway(s).

  1. Breast cancer and post-menopausal hormone therapy.

    Science.gov (United States)

    Kenemans, P; Bosman, A

    2003-03-01

    From the introduction of post-menopausal hormone replacement therapy (HRT) there has been great concern that HRT could possibly increase the risk of breast cancer. Prolonged exposure to endogenous oestrogens undeniably increases the risk of breast cancer. Questions that are important and until now only partly answered, are the following. Are oestrogens tumour promoters, as they induce mitosis, lead to proliferation and, therefore, accelerated growth of clinically occult pre-existing tumours? In addition to this, are they genotoxic mutagenic carcinogens, or could they initiate tumours by way of accumulation of incessant DNA-replication damage mechanism? Opinions vary as to the effect of the addition of a progestogen. There is a multitude of different progestogens which could bind with differing affinity to progesterone receptor PR-A or PR-B, and which have different physiological functions via differential gene regulation. The action of a progestogen on the oestrogen-induced cellular mitotic activity could be synergistic or antagonistic (by different pathways: oestrogen receptor downregulation, activating of metabolic pathways within the breast or stimulation of apoptosis)? Over 60 observational studies and two randomized trials provide evidence that the small but significant increase in risk appears with long-term current post-menopausal hormone use. The addition of a progestogen does not decrease the risk as seen with oestrogens alone and might increase the risk further. It is not clear whether there is a difference in risk with sequentially combined versus continuously combined HRT. Many questions nevertheless still remain. Is the risk increase limited to lean women only? What about risk-modifying factors such as alcohol use and a positive family history for breast cancer? Are tumours detected under HRT less aggressive, is there a better prognosis and is the mortality not increased while morbidity is? And is HRT contraindicated for women with a positive family

  2. Clinical efficacy and safety of gefitinib versus pemetrexed second line treatment of non-small cell lung cancer%吉非替尼对比培美曲塞治疗晚期非鳞非小细胞肺癌的临床疗效及安全性评价

    Institute of Scientific and Technical Information of China (English)

    刘孝民

    2015-01-01

    目的:比较吉非替尼与培美曲塞治疗晚期非鳞非小细胞肺癌的临床疗效及安全性。方法将42例既往含铂化疗失败的晚期非鳞非小细胞肺癌患者随机分为试验组20例和对照组22例。试验组予以口服吉非替尼250 mg,每日一次,连续服用至疾病进展或出现不可耐受性不良反应。对照组予以静脉滴注500 mg・ m-2培美曲塞,第1,21天重复一次,直至患者出现疾病进展或不可耐受不良反应。比较2组患者的临床疗效及化疗相关不良反应的发生情况。结果治疗后,试验组的客观缓解率为20.00%(4/20),疾病控制率为35.00%(7/20),对照组的客观缓解率为13.64%(3/22),疾病控制率为36.36%(8/22),2组比较差异均无统计学意义(P>0.05)。试验组与对照组的中位无进展生存时间分别为13.60周和13.20周( P>0.05)。试验组的不良反应为皮疹8例(40.00%)和腹泻3例(15.00%),对照组的不良反应为粒细胞减少8例(36.36%)和乏力9例(40.91%,P>0.05)。结论吉非替尼与培美曲塞治疗晚期非鳞非小细胞肺癌的临床疗效相当,但不良反应各异。%Objective To evaluated the activity and safety of gefitinib versus pemetrexed treatment of advanced non-squamous cell non-small cell lung cancer ( NSCLC ) .Methods Forty two non -squamous cell NSCLC patients previously treated with platinum based chemotherapy reg-imen were recruited in this study and randomly divided into experiment group (n=20) and control group(n=22).Patients in the experiment group were administered gefitinib 250 mg orally per day until dead or pro-gression.Patients in the control group were administered 500 mg・ m2 pemetrexed intervenous drop infusion day 1 every 21 days until dead or progression.The clinical efficacy and drug associated toxicity was evalua-ted between the two groups. Results The objective

  3. Poor response to gefitinib in lung adenocarcinoma with concomitant epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

    Science.gov (United States)

    Zhou, Jianya; Zheng, Jing; Zhao, Jing; Sheng, Yihong; Ding, Wei; Zhou, Jianying

    2015-03-01

    A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant ALK rearrangement and exon 19 (E746-A750del) EGFR mutation. The ALK rearrangement was confirmed not only in the primary tumor biopsy specimen, but also in the pleural effusion cell block by reverse transcriptase-polymerase chain reaction (RT-PCR), Ventana ALK immunohistochemistry assay, and fluorescence in situ hybridization. No clinical benefit using chemotherapy or EGFR tyrosine kinase inhibitor gefitinib was obtained in this case.

  4. 吉非替尼记名供药计划治疗晚期复发非小细胞肺癌的疗效和预后因素分析%Analysis of the efficacy and safety of gefitinib in the treatment of recurrent advanced non-small cell lung cancer in an expanded access program (EAP)

    Institute of Scientific and Technical Information of China (English)

    黄河; 张阳; 赵洪云; 王志强; 徐菲; 徐光川; 张力; 管忠震

    2009-01-01

    Objective The aim of this study is to evaluate the efficacy and safety of Gefitinib in the treatment of Chinese patients with recurrent advanced non-small-cell lung cancer (NSCLC). Methods 120 patients were enrolled in this trial from September 2002 to March 2005, and 103 patients were evaluable. All patients were histologically or/and cytologically confirmed to have a locally advanced or metastatic NSCLC, and failed to previous standard treatments. The patients received orally 250 mg of Gefitinib once daily until the disease progression or intolerance to toxicity. First evaluation of response was undertaken one month after drug initiation, then every 2 or 3 months till disease progression. Each patient was followed up every 6 months untill death or end of follow-up. Results Among the 103 evaluable patients, the objective response rate was 18.4% (19/103), and the disease control rate was 51.5% (53/103). The median time to progression (mTTP) was 3 months (range: 0.2~40), the median survival time (MST) was 9.8 months (range: 0.5~51), the 1-, 2-, 3-year survival rates were 44.7%, 26.4% and 13.2%, respectively. The TIP of 41 patients was longer than 6 months with a MST of 25.5 months. The results of COX model analysis suggested that the patients with adenocarcinoma, rash and favourable performance status (PS) had longer TIP. The patients with favourable PS and well controlled disease had longer survival time. Adverse events included skin rash, dry skin, diarrhea and elevation of serum glutamate pyruvate transaminase (SGPT), and were usually mild. Conclusion Gefitinib is effective in treatment of patient with recurrent advanced NSCLC. The patients with controlled disease may achieve a long survival, and the adverse reactions are mild and tolerable.%目的 研究吉非替尼治疗中国晚期非小细胞肺癌(NSCLC)患者的安全性和疗效.方法 2002年9月至2005年3月共入选晚期复发NSCLC患者120例,其中可评价疗效者103例.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    Griffin, Yvette

    2016-08-01

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

  8. 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.

  9. Efficacy of gamma knife combined with gefitinib for non-small cell lung cancer patients with brain metastases%伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析

    Institute of Scientific and Technical Information of China (English)

    王建军; 陈绍华; 李国明; 杜熙

    2016-01-01

    目的:探讨伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析。方法将71例非小细胞肺癌脑转移瘤患者分为2组。观察组采用伽玛刀联合吉非替尼治疗,对照组采用全脑放射疗法联合吉非替尼治疗。对比2组患者的疗效、生存质量、生存率、不良反应。结果观察组和对照组总有效率(91.67% vs 82.86%)与控制率(97.22% vs 94.29%)比较差异均无统计学意义(χ2值分别为1.244、0.378,P 值均>0.05);观察组 Karofsky 得分有效率(72.22%)显著高于对照组(45.71%)(χ2=5.161,P0.05);观察组脱发、头痛、肝功能损害的发生率显著低于对照组(χ2值分别为27.070、17.154、6.693,P值均0.05). The effective rate in the observation group was significantly higher than that in the control group (72.22% vs 45.71%,χ2=5.161,P 0.05).The incidence of hair loss,headache,and liver function damage in the observation group was significantly lower than that in the control group (χ2 =27.070,17.154,6.693,respectively,all P <0.05).Conclusions Gamma knife combined with gefitinib has curative effect in the treatment of non-small cell lung cancer with brain metastasis,can better control the progression of the tumor,increase the survival rate,has small toxic and side effect,and effectively improve the quality of life of patients.

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

    NARCIS (Netherlands)

    Scholten, E.T.; Horeweg, N.; Koning, H.J. de; Vliegenthart, R.; Oudkerk, M.; Mali, W.P.; Jong, P.A. de

    2015-01-01

    OBJECTIVES: To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. METHODS: 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 re

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-β signaling pathway.

    Science.gov (United States)

    Li, Li; Huang, Wenting; Li, Kunlin; Zhang, Kejun; Lin, Caiyu; Han, Rui; Lu, Conghua; Wang, Yubo; Chen, Hengyi; Sun, Fenfen; He, Yong

    2015-12-22

    Interstitial lung disease (ILD) is a serious side-effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Therefore, it is necessary to study underlying mechanisms for the development of pulmonary fibrosis induced by EGFR-TKI and potential approaches to attenuate it. Metformin is a well-established and widely prescribed oral hypoglycemic drug, and has gained attention for its potential anticancer effects. Recent reports have also demonstrated its role in inhibiting epithelial-mesenchymal transition and fibrosis. However, it is unknown whether metformin attenuates EGFR-TKI-induced pulmonary fibrosis. The effect of metformin on EGFR-TKI-induced exacerbation of pulmonary fibrosis was examined in vitro and in vivo using MTT, Ki67 incorporation assay, flow cytometry, immunostaining, Western blot analysis, and a bleomycin-induced pulmonary fibrosis rat model. We found that in lung HFL-1 fibroblast cells, TGF-β or conditioned medium from TKI-treated lung cancer PC-9 cells or conditioned medium from TKI-resistant PC-9GR cells, induced significant fibrosis, as shown by increased expression of Collegen1a1 and α-actin, while metformin inhibited expression of fibrosis markers. Moreover, metformin decreased activation of TGF-β signaling as shown by decreased expression of pSMAD2 and pSMAD3. In vivo, oral administration of gefitinib exacerbated bleomycin-induced pulmonary fibrosis in rats, as demonstrated by HE staining and Masson staining. Significantly, oral co-administration of metformin suppressed exacerbation of bleomycin-induced pulmonary fibrosis by gefitinib. We have shown that metformin attenuates gefitinib-induced exacerbation of TGF-β or bleomycin-induced pulmonary fibrosis. These observations indicate metformin may be combined with EGFR-TKI to treat NSCLC patients.

  14. Analysis of Prognostic Factors of 80 Advanced NSCLC Patients Treated with Gefitinib for more than 6 Months

    Directory of Open Access Journals (Sweden)

    Ling DAI

    2010-11-01

    Full Text Available Background and objective Some clinical predictors can be used to evaluate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI therapy for non-small cell lung cancer (NSCLC, including female, East-Asian, non-smoker, adenocarcinoma, skin rash, etc. The aim of this study is to explore the prognosis of advanced NSCLC patients treated with gefitinib for more than 6 months. Methods Eighty advanced NSCLC patients treated with gefitinib for more than 6 months were collected from January, 2005 to March, 2010. The association of their clinical characteristics with median progression-free survival time (PFS was analysed. Results Significantly longer median PFS were found in patients with > 70 years old, earlier clinical stage (IIIb, non-bone metastasis (27 months vs 12 months; 32 months vs 12 months; 16 months vs 10 months, P < 0.05. There was no significant difference in median PFS between ECOG performance status 0-1 group and 2-4 group, between more than 4 cycles of chemotherapy and 1-4 cycles, between PFS of chemotherapy > 6 months group and ≤6 months group, however, ECOG 0-1 group and more than 4 cycles of chemotherapy or PFS of chemotherapy > 6 months group seemed to have longer median PFS (15 months vs 10 months; 16 months vs 12 months; 14months vs 12 months. Compared with no skin rash and grade 0-I rash group, the patients with rash or grade ≥II rash had longer median PFS (16 months vs 13 months, P=0.171; 19 months vs 11 months, P=0.085. The median PFS was not related with sex, smoking index, pathological types, metastatic sites except bone, treatment strategy, etc (P > 0.05. Conclusion For gefitinib treatment, longer median PFS is likely to be obtained in patients with > 70 years old, earlier clinical stage (IIIb, non-bone metastasis.

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

    Science.gov (United States)

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

    2016-05-01

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

  16. Des-Gamma-Carboxy Prothrombin (DCP Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Zhang

    2015-01-01

    Full Text Available Background/Aims: Des-gamma-carboxy prothrombin (DCP, an aberrant prothrombin produced by hepatocellular carcinoma (HCC cells, is known as a marker for HCC. Recent studies indicated that high levels of DCP are associated with the malignant potential of HCC. In this study, we aimed to investigate the association of DCP with gefitinib treatment failure in HCC and whether DCP counteracts gefitinib-induced growth inhibition and apoptosis of HCC. Methods: The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT assay. Apoptotic cells were identified by Annexin V-FITC/PI staining. Western blotting was performed to analyze the expressions of molecules related to the apoptotic caspase-dependent pathway and epidermal growth factor receptor (EGFR pathway. Results: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of proliferation and stimulation of apoptosis. DCP prevented the activation of the apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic effects of DCP also arose from its ability to up-regulate EGFR, c-Met and hepatocyte growth factor (HGF in HCC cells. Conclusion: DCP antagonized gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up-regulating the EGFR pathway. High levels of DCP might thus lead to low response rates or possibly no response to gefitinib in patients with HCC.

  17. Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with {sup 211}At-EGF

    Energy Technology Data Exchange (ETDEWEB)

    Sundberg, Aasa Liljegren; Orlova, Anna; Gedda, Lars; Tolmachev, Vladimir; Carlsson, Joergen [Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala (Sweden); Almqvist, Ylva [Division of Radiology, Uppsala University, Uppsala (Sweden); Blomquist, Erik [Division of Oncology, Uppsala University, Uppsala (Sweden); Jensen, Holger J. [Department of Clinical Physiology and Nuclear Medicine, PET and Cyclotron Unit, Rigshospitalet, Copenhagen (Denmark)

    2003-10-01

    The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ['Iressa' (trademark of the AstraZeneca group of companies), ZD1839] increases the cellular uptake of radiolabelled epidermal growth factor (EGF). We investigated gefitinib treatment combined with astatine-211 EGF targeting in vitro using two cell lines expressing high levels of EGFR: A431 (sensitive to gefitinib) and U343MGaCl2:1 (resistant to gefitinib). In both cell lines, the uptake of {sup 211}At-EGF was markedly increased by concomitant treatment with gefitinib. Survival was investigated using both a clonogenic survival assay and a cell growth assay. Combined gefitinib and {sup 211}At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with {sup 211}At-EGF alone. In A431 cells, {sup 211}At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. These results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours and decrease the effect of such therapy in gefitinib-sensitive tumours. (orig.)

  18. 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.)

  19. 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.…

  20. 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

    PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been introduced as antitumor agents in the treatment of cancers overexpressing the receptor. The treatment has gastrointestinal side effects which may decrease patient compliance and limit the efficacy. Glucagon...... and cross-sectional area were decreased. The same parameters were increased by GLP-2 treatment alone, and when GLP-2 was combined with the gefitinib treatment, the parameters remained unchanged. CONCLUSIONS: Treatment with an EGFR tyrosine kinase inhibitor in mice results in small-intestinal growth...... inhibition that can be completely prevented by simultaneous treatment with GLP-2. This suggests that the gastrointestinal side effects elicited by treatment with EGFR tyrosine kinase inhibitors can be circumvented by GLP-2 treatment....

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

    Directory of Open Access Journals (Sweden)

    Jennifer M. Hulett

    2015-05-01

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

  2. 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.)

  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

    2017-01-10

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  5. Molecular Factors Related to Gefitinib Efficacy in Advanced Non-small Cell Lung Cancer%吉非替尼治疗晚期非小细胞肺癌疗效的相关分子生物学因素研究进展

    Institute of Scientific and Technical Information of China (English)

    吕平; 周涛

    2010-01-01

    @@ 非小细胞肺癌(non-small cell lung caner,NSCLC)占肺癌的80%,确诊时多为晚期.虽然手术、化疗、放疗技术在不断提高,但NSCLC患者的预后仍然很差,总体5年生存率仍然小于20%[1].近年来一些针对肿瘤特定分子靶点的抗肿瘤靶向药物显示了一些疗效,其中以表皮生长因子受体(epidermal growth factor receptor,EGFR)为靶点的EGFR酪氨酸激酶抑制剂(EGFR tyrosine kinasesinhibitor,EGFR-TKI)吉非替尼(Gefitinib)在NSCLC的治疗中显示了一定的疗效.

  6. Post-translational regulation of COX2 activity by FYN in prostate cancer cells

    OpenAIRE

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-01-01

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates h...

  7. Post-traumatic Stress Symptoms among Iranian Parents of Children during Cancer Treatment.

    Science.gov (United States)

    Iranmanesh, Sedigheh; Shamsi, Ala; Dehghan, Mahlegha

    2015-04-01

    Support of parents of children with cancer requires healthcare personnel to be knowledgeable about the prevalence of post-traumatic stress symptoms among Iranian parents of children with cancer. This study was conducted to fulfill this aim in the South-East of Iran. Using the Impact of Event Scale -Revised, for parents of children with cancer, 200 parents in two hospitals supervised by Kerman University of Medical Sciences, were assessed. The total mean score of post-traumatic stress symptoms was 41.70. Among all categories of the Impact of Event Scale -Revised, the highest mean belonged to the category of 'intrusion' 16.03 (SD  =  6.24) and the lowest one belonged to the category of 'hyperarousal' 10.68 (SD  =  4.58). Based on the results, mothers had higher post-traumatic stress symptoms compared with fathers (p post-traumatic stress symptoms among mothers was 2.49 times more than that among fathers (p  =  0.01). There was no association between sociodemographic data and post-traumatic stress symptoms. More research is needed to elucidate the Iranian parents' experience of having children with cancer.

  8. 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...

  9. 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.

  10. 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

  11. Post-traumatic Stress Symptoms and Post-traumatic Growth in 223 Childhood Cancer Survivors: Predictive Risk Factors.

    Science.gov (United States)

    Tremolada, Marta; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

    2016-01-01

    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 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 (PTSSs), 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 (R (2) = 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 (R (2) = 0.36; F = 9.1; p = 0.0001), with

  12. 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....

  13. 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...

  14. Hospital volume and post-operative mortality after resection for gastric cancer

    NARCIS (Netherlands)

    Damhuis, RAM; Meurs, CJC; Dijkhuis, CM; Stassen, LPS; Wiggers, T

    2002-01-01

    Aims: In low-volume hospitals, expertise in gastric surgery is difficult to maintain because of the decreasing incidence of gastric cancer and the fall of surgery for ulcer disease. We evaluated the prognostic impact of hospital volume on post-operative mortality (POM) in a consecutive series of 197

  15. Patients with ovarian cancer have elevated (51)Cr-EDTA plasma clearance early post-operatively

    DEFF Research Database (Denmark)

    Nielsen, S S; Havsteen, H; Petersen, L K;

    2002-01-01

    Plasma clearance of (51)Cr-EDTA (Clp(EDTA)) is widely used to determine glomerular filtration rate prior to carboplatin based chemotherapy. We have observed that many patients with ovarian cancer have elevated Clp in the early post-operative phase compared to later phases. The purpose of this stu...

  16. 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 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.

  17. 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.

  18. Cytotoxic and apoptotic effects of bortezomib and gefitinib compared to alkylating agents on human glioblastoma cells.

    Science.gov (United States)

    Pédeboscq, Stéphane; L'Azou, Béatrice; Passagne, Isabelle; De Giorgi, Francesca; Ichas, François; Pometan, Jean-Paul; Cambar, Jean

    2008-01-01

    Glioblastoma is a malignant astrocytic tumor with a median survival of about 12 months for which new therapeutic strategies are required. We therefore examined the cytotoxicity of anticancer drugs with different mechanisms of action on two human glioblastoma cell lines expressing various levels of EGFR (epidermal growth factor receptor). Apoptosis induced by these anticancer agents was evaluated by flow cytometry. The cytotoxicity of alkylating drugs followed a dose-effect curve and cytotoxicity index values were lower with carboplatin than with BCNU and temozolomide. Anti-EGFR gefitinib (10 microM) cytotoxicity on DBTRG.05-MG expressing high levels of EGFR was significantly higher than on U87-MG expressing low levels of EGFR. Carboplatin and temozolomide cytotoxicity was potentiated with the addition of gefitinib on DBTRG.05-MG. Among the anticancer agents tested, the proteasome inhibitor bortezomib was the most cytotoxic with very low IC50 on the two cell lines. Moreover, all anticancer drugs tested induced apoptosis in a concentration-dependent manner. Bortezomib proved to be a more potent inductor of apoptosis than gefitinib and alkylating agents. These results show the efficacy of bortezomib and of the association between conventional chemotherapy and gefitinib on glioblastoma cells and therefore suggest the interest of these molecules in the treatment of glioblastoma.

  19. Automated synthesis of [18F]gefitinib on a modular system

    NARCIS (Netherlands)

    Läppchen, T.; Vlaming, M.L.H.; Custers, E.; Lub, J.; Sio, C.F.; DeGroot, J.; Steinbach, O.C.

    2012-01-01

    In recent years, [ 18F]gefitinib PET has successfully been employed for a number of applications ranging from oncology to in vivo studies of drug transporter proteins. We here report a reliable, automated procedure for routine synthesis of this radiotracer on an Eckert and Ziegler modular system. Th

  20. 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...

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

    Science.gov (United States)

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

    2008-01-01

    This case describes a 71 year old, post-menopausal woman who developed vaginal discharge. This complaint ultimately led to the discovery of bowel cancer in conjunction with a large sterile pyometra. The pyometra was not due to genital malignancy. The most likely conclusion is that the pyometra may have arisen as an inflammatory response to the adjacent bowel pathology. This case report highlights the need for clinicians to consider non-gynaecological cancer as a possible cause for otherwise unexplained pyometra. PMID:18606021

  2. Mechanisms underlying social inequality in post-menopausal breast cancer.

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  3. Post-translational regulation of COX2 activity by FYN in prostate cancer cells.

    Science.gov (United States)

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-06-30

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.

  4. Clinical observation of maintenance therapy with gefitinib after the first-line chemotherapy for patients with advanced non-small-cell lung cancer%一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    姜海英; 谢晓东; 朱梅

    2011-01-01

    Objective To evaluate RR,DCR,PFS,OS and toxicities in a population affected by NSCLC using gefitinib as maintenance therapy after the first line chemotherapy.Methods From January,2006 to January,2008,seventy-one patients were enrolled with stable disease or partial response after firstline chemotherapy.They were divided into the observing group and the control group.Gefitinib was administered at the dose of 250 mg in observing group;placebo was also administered everyday in control group.Results Of 71 assessable patients ,overall response rate was 36.1% (13/36) in observing group and 14.3 % (5/35) in control group respectively (x 2 = 4.633,P = 0.036),and one patient (2.8 %) was observed complete response (CR) in observing group.The disease control rate was 83.3 % (30/36) in observing group and 42.9 % (15/35) in control group,respectively,(x2 = 14.782,P < 0.001).The median PFS (progression free survival time) was 13 weeks in observing group and 11 weeks in control group respectively (x2 = 10.401,P =0.001).The median overall survival time (OS) was 13.2 months in observing group and 10.4 months in control group respectively (x2 = 7.696,P= 0.006).The median OS was 18.5 months in women and 11.2 months in men(x2 =22.864,P=0.011) .The median OS was 15.3 months in non-smokers and 10.3 months in smokers (x2 =10.389,P =0.007).The median OS was 16.0 months in adenocarcinoma and alveolar cell carcinoma patients and 10.2 months in squamous cell carcinoma patients (x 2 = 4.638,P = 0.001).The most common toxicity was rash ,diarrhea,fatigue and dry skin itching,and most of them were 1 or 2 grade.Conclusion Maintenance therapy with gefitinib after first-line chemotherapy may improve overall survival time and progression free survival time in patients with NSCLC,and it is effective and safe.%目的 评价晚期非小细胞肺癌(NSCLC)一线化疗获得部分缓解(PR)或稳定(SD)后予以吉非替尼单药维持治疗的临床疗效.方法 应用前瞻性随

  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

    2016-10-11

    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. Lifetime exercise activity and breast cancer risk among post-menopausal women.

    Science.gov (United States)

    Carpenter, C L; Ross, R K; Paganini-Hill, A; Bernstein, L

    1999-08-01

    Lifetime exercise activity has been linked to breast cancer risk among young women. However, no study has specifically evaluated whether lifetime exercise activity is related to the breast cancer risk of post-menopausal women. We conducted a population-based case-control study of post-menopausal white women (1123 newly diagnosed cases and 904 healthy controls) aged 55-64 who lived in Los Angeles County, California, USA to evaluate this relationship. Although neither exercise activity from menarche to age 40 years, nor exercise after age 40 separately predicted breast cancer risk, risk was lower among women who had exercised each week for at least 17.6 MET-hours (metabolic equivalent of energy expenditure multiplied by hours of activity) since menarche than among inactive women (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.37-0.83). Exercise activity was not protective for women who gained considerable (> 17%) weight during adulthood. However, among women with more stable weight, breast cancer risk was substantially reduced for those who consistently exercised at high levels throughout their lifetime (OR = 0.42; 95% CI 0.24-0.75), those who exercised more than 4 h per week for at least 12 years (OR = 0.59; 95% CI 0.40-0.88), and those who exercised vigorously (24.5 MET-hours per week) during the most recent 10 years (OR = 0.52; 95% CI 0.32-0.85). Strenuous exercise appears to reduce breast cancer risk among post-menopausal women who do not gain sizable amounts of weight during adulthood.

  7. [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.

  8. Positron Emission Tomography and head and neck cancers: Recurrence and post-treatment surveillance; TEP au {sup 18}-FDG et cancers ORL: recidive et surveillance post-therapeutique

    Energy Technology Data Exchange (ETDEWEB)

    Colavolpe, C.; Guedj, E.; Tessonnier, L.; Mundler, O. [CHU La Timone, Service Central de Biophysique et de Medecine Nucleaire, 13 - Marseille (France); Fakhry, N.; Zanaret, M. [CHU La Timone, Service d' ORL et de Chirurgie Cervicofaciale, 13 - Marseille (France)

    2008-08-15

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

  9. Efficacy of small bowel displacement system in post-operative pelvic radiation therapy of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Yong Chan; Lim, Do Hoon; Kim, Moon Kyung; Wu, Hong Gyun; Kim, Dae Yong; Huh, Seung Jae [Samsung Medical Center, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-03-01

    This study is to evaluate the efficacy of small bowel displacement system(SBDS) in post-operative pelvic radiation therapy(RT) of rectal cancer patients by measurement of small bowel volume included in the radiation fields receiving therapeutic dose. Ten consecutive new rectal cancer patients referred to the department of Radiation Oncology of Samsung Medical Center in May of 1997 were included in this study. All patients were asked to drink Gastro-graphin before simulation and were laid prone for conventional simulation and CT scans with and without SBDS. The volume of opacified small bowel on CT scans, which was to be included in the radiation fields receiving therapeutic dose, was measured using picture archiving and communication system(PACS). The average small bowel volumes with and without SBDS were 176.0ml(5.2-415.6ml) and 185.1m;(54.5-434.2ml), respectively. the changes of small bowel volume with SBDS compared to those without SBDS were more than 10% decrease in three, less than 10% decrease in two, less than 10% increase in three, and more than 10% increase in two patients. No significant advantage of using SBDS in post-operative pelvic RT for rectal cancer patients has been shown by small bowel volume measurement using CT scan considering additional effort and time needed for simulation and treatment setup.

  10. 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.)

  11. Phase II Trials of Erlotinib or Gefitinib in Patients with Recurrent Meningioma

    Science.gov (United States)

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

    2013-01-01

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

  12. Coping strategies predict post-traumatic stress in patients with head and neck cancer.

    Science.gov (United States)

    Richardson, Amy E; Morton, Randall P; Broadbent, Elizabeth

    2016-10-01

    Evidence suggests that patients with head and neck cancer (HNC) are susceptible to post-traumatic stress disorder (PTSD). However, research is yet to examine predictors of PTSD symptoms in this patient group. The objective of this study was to investigate whether coping strategies at HNC diagnosis were related to outcomes of post-traumatic stress and health-related quality of life (HRQL) 6 months later. Sixty-five patients with HNC completed an assessment of coping, distress, and health-related quality of life at diagnosis and again 6 months later, and an assessment of post-traumatic stress at 6 months. Correlations and regression analyses were performed to examine relationships between coping and outcomes over time. Regression analyses showed that denial, behavioural disengagement and self-blame at diagnosis predicted post-traumatic stress symptoms. Self-blame at diagnosis also predicted poor HRQL. Results have implications for the development of psychological interventions that provide alternative coping strategies to potentially reduce PTSD symptoms and improve HRQL.

  13. Successful EGFR-TKI rechallenge of leptomeningeal carcinomatosis after gefitinib-induced interstitial lung disease.

    Science.gov (United States)

    Nakamichi, Shinji; Kubota, Kaoru; Horinouchi, Hidehito; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Tamura, Tomohide

    2013-04-01

    We report the case of a 49-year-old non-smoking Japanese woman with backache and difficulty in walking. She was diagnosed as having advanced lung adenocarcinoma, and an epithelial growth factor receptor mutation (in-frame deletions in exon 19) was found. After radiation therapy of bone metastases with spinal cord compression and brain metastases, gefitinib was administered. On day 2, she developed acute interstitial lung disease. Gefitinib therapy was discontinued and treatment with high-dose steroid therapy improved the interstitial lung disease. Cisplatin plus pemetrexed was initiated as second-line chemotherapy, but she was hospitalized again for leptomeningeal carcinomatosis. Considering the poor prognosis of leptomeningeal carcinomatosis, we decided that erlotinib was our only choice of treatment. As a third-line treatment, erlotinib was administered after informing the patient about the high risk of interstitial lung disease. Neurological symptoms were improved within a week and interstitial lung disease did not recur. The patient has received erlotinib successfully for 18 months without the recurrence of leptomeningeal carcinomatosis. Erlotinib rechallenge after gefitinib-induced interstitial lung disease must be carefully chosen based on the balance of a patient's risk and benefit.

  14. The emerging immunological role of post-translational modifications by reactive nitrogen species in cancer microenvironment

    Directory of Open Access Journals (Sweden)

    Francesco eDe Sanctis

    2014-02-01

    Full Text Available Under many inflammatory contexts, such as tumor progression, systemic and peripheral immune response is tailored by reactive nitrogen species (RNS-dependent post-translational modifications, suggesting a biological function for these chemical alterations. RNS modify both soluble factors and receptors essential to induce and maintain a tumor-specific immune response, creating a chemical barrier that impairs effector T cell infiltration and functionality in tumor microenvironment and supports the escape phase of cancer. RNS generation during tumor growth mainly depends on nitric oxide production by both tumor cells and tumor-infiltrating myeloid cells that constitutively activate essential metabolic pathways of L-arginine catabolism. This review provides an overview of the potential immunological and biological role of RNS-induced modifications and addresses new approaches targeting RNS either in search of novel biomarkers or to improve anti-cancer treatment.

  15. The emerging immunological role of post-translational modifications by reactive nitrogen species in cancer microenvironment.

    Science.gov (United States)

    De Sanctis, Francesco; Sandri, Sara; Ferrarini, Giovanna; Pagliarello, Irene; Sartoris, Silvia; Ugel, Stefano; Marigo, Ilaria; Molon, Barbara; Bronte, Vincenzo

    2014-01-01

    Under many inflammatory contexts, such as tumor progression, systemic and peripheral immune response is tailored by reactive nitrogen species (RNS)-dependent post-translational modifications, suggesting a biological function for these chemical alterations. RNS modify both soluble factors and receptors essential to induce and maintain a tumor-specific immune response, creating a "chemical barrier" that impairs effector T cell infiltration and functionality in tumor microenvironment and supports the escape phase of cancer. RNS generation during tumor growth mainly depends on nitric oxide production by both tumor cells and tumor-infiltrating myeloid cells that constitutively activate essential metabolic pathways of l-arginine catabolism. This review provides an overview of the potential immunological and biological role of RNS-induced modifications and addresses new approaches targeting RNS either in search of novel biomarkers or to improve anti-cancer treatment.

  16. Post-Radiation Metabolic Tumor Volume Predicts Outcome in Head-and-Neck Cancer

    Science.gov (United States)

    Murphy, James D; La, Trang H.; Chu, Karen; Quon, Andrew; Fischbein, Nancy J.; Maxim, Peter G.; Graves, Edward E.; Loo, Billy W.; Le, Quynh-Thu

    2010-01-01

    Purpose To explore the prognostic value of metabolic tumor volume measured on post-radiation 18F-fluorodeoxyglucose positron emission tomography (PET) imaging in head-and-neck cancer patients. Methods and Materials Forty-seven head-and-neck cancer patients who received pre- and post-treatment PET/CT imaging along with definitive chemoradiotherapy were included in this study. PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV2.0-MTV4.0; where MTV2.0 refers to the volume above an SUV threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox-regression models were used to test for association between PET endpoints and disease-free survival (DFS) and overall survival (OS). Results Multiple post-radiation PET endpoints correlated significantly with outcome, however the most robust predictor of disease progression and death was MTV2.0. An increase in MTV2.0 of 21cm3 (difference between 75th and 25th percentile) was associated with an increased risk of disease progression (hazard ratio [HR]=2.5, p=0.0001) and death (HR=2.0, p=0.003). In patients with non-nasopharyngeal carcinoma (non-NPC) histology (n=34), MTV2.0<18cm3 and MTV2.0≥18cm3 yielded 2-year DFS rates of 100% and 63%, respectively (p=0.006) and 2-year OS rates of 100% and 81%, respectively (p=0.009). There was no correlation between MTV2.0 and DFS or OS with NPC histology (n=13). On multivariate analysis only post-radiation MTV2.0 was predictive of DFS (HR=2.47, p=0.0001) and OS (HR=1.98, p=0.003). Conclusions Post-radiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification, and will be valuable in the future with risk-adapted therapies. PMID:20646870

  17. A tissue biomarker panel predicting systemic progression after PSA recurrence post-definitive prostate cancer therapy.

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    Tohru Nakagawa

    Full Text Available BACKGROUND: Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy. METHODOLOGY/PRINCIPAL FINDINGS: A case-control design was used to test the association of gene expression with outcome. Systemic (SYS progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancer-related genes were evaluated-including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84-0.92. Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases and systemic progression beyond 5 years (in PSA controls with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005. Genes mapped to 8q24 were significantly enriched in the model. CONCLUSIONS/SIGNIFICANCE: Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence.

  18. Gefitinib induces epidermal growth factor receptor dimers which alters the interaction characteristics with ¹²⁵I-EGF.

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    Hanna Björkelund

    Full Text Available The tyrosine kinase inhibitor gefitinib inhibits growth in some tumor types by targeting the epidermal growth factor receptor (EGFR. Previous studies show that the affinity of the EGF-EGFR interaction varies between hosting cell line, and that gefitinib increases the affinity for some cell lines. In this paper, we investigate possible mechanisms behind these observations. Real-time interaction analysis in LigandTracer® Grey revealed that the HER2 dimerization preventing antibody pertuzumab clearly modified the binding of ¹²⁵I-EGF to EGFR on HER2 overexpressing SKOV3 cells in the presence of gefitinib. Pertuzumab did not affect the binding on A431 cells, which express low levels of HER2. Cross-linking measurements showed that gefitinib increased the amount of EGFR dimers 3.0-3.8 times in A431 cells in the absence of EGF. In EGF stimulated SKOV3 cells the amount of EGFR dimers increased 1.8-2.2 times by gefitinib, but this effect was cancelled by pertuzumab. Gefitinib treatment did not alter the number of EGFR or HER2 expressed in tumor cell lines A431, U343, SKOV3 and SKBR3. Real-time binding traces were further analyzed in a novel tool, Interaction Map, which deciphered the different components of the measured interaction and supports EGF binding to multiple binding sites. EGFR and HER2 expression affect the levels of EGFR monomers, homodimers and heterodimers and EGF binds to the various monomeric/dimeric forms of EGFR with unique binding properties. Taken together, we conclude that dimerization explains the varying affinity of EGF-EGFR in different cells, and we propose that gefitinib induces EGFR dimmers, which alters the interaction characteristics with ¹²⁵I-EGF.

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

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    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.)

  20. 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.

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

    Science.gov (United States)

    Zak, Marek; Biskup, Malgorzata; Macek, Pawel; Krol, Halina; Krupnik, Szymon; Opuchlik, Anna

    2017-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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

  2. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.

    Science.gov (United States)

    Bria, Emilio; Pilotto, Sara; Amato, Eliana; Fassan, Matteo; Novello, Silvia; Peretti, Umberto; Vavalà, Tiziana; Kinspergher, Stefania; Righi, Luisella; Santo, Antonio; Brunelli, Matteo; Corbo, Vincenzo; Giglioli, Eliana; Sperduti, Isabella; Milella, Michele; Chilosi, Marco; Scarpa, Aldo; Tortora, Giampaolo

    2015-05-20

    Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.

  3. Accumulation efficiency of cancer stem-like cells post {gamma}-ray and proton irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Quan Yi; WangWeikang; Fu Qibin; Mei Tao; Wu Jingwen; Li Jia [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Yang, Gen, E-mail: gen.yang@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Wang Yugang [State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China)

    2012-09-01

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

  4. 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.

  5. An analysis of Social Work Oncology Network Listserv Postings on the Commission of Cancer's distress screening guidelines.

    Science.gov (United States)

    Burg, Mary Ann; Adorno, Gail; Hidalgo, Jorge

    2012-01-01

    This is a qualitative study of listserv postings by members of the Social Work Oncology Network (SWON) in response to the Commission on Cancer's 2011 guidelines for distress screening of cancer patients. Archived listserv postings for the period of December 2010 to November 2011 were deidentified and a sample was derived by a list of keywords for the analysis. Aims of the study included describing the general categories and themes of the postings devoted to the new distress screening standard and examining the process of facilitation of mutual support and information exchange by oncology social workers in response to the new screening standards. During the 12-month timeframe there were 242 unique listserv postings sampled for the analysis. Oncology social worker (OSW) discussion of the distress screening guidelines remained a constant topic over the 12 months, and major themes that emerged from the data included processes of implementation of distress screening in cancer centers, screening policies and protocols, screening tool choice, and oncology social worker professional identity. The SWON listserv members used the listserv as a mechanism to post their requests for information on screening, to share their experiences in the beginning stages of implementing the guidelines, and to build support for legitimizing oncology social workers as the lead profession in the implementation of the guidelines in member cancer centers.

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  7. 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.

  8. Post-operative pain management in head and neck cancer patients: predictive factors and efficacy of therapy.

    Science.gov (United States)

    Bianchini, C; Malagò, M; Crema, L; Aimoni, C; Matarazzo, T; Bortolazzi, S; Ciorba, A; Pelucchi, S; Pastore, A

    2016-04-01

    There is increasing interest about all aspects of pain sensation for patients undergoing head and neck surgery, and efforts have been made to better assess, monitor and reduce the occurrence of pain. The aetiology of pain is considered to be "multifactorial", as it is defined by several features such as personal experience, quality perception, location, intensity and emotional impact. The aim of this paper is: (i) to evaluate the efficacy of analgesic treatment in patients with head and neck cancer treated by surgery, and (ii) to study the variables and predictive factors that can influence the occurrence of pain. A total of 164 patients, affected by head and neck cancer and surgically treated, between December 2009 and December 2013, were included in this study. Data collected include age, gender, assessment of anaesthetic risk, tumour localisation, pathological cancer stage, TNM stage, type of surgery performed, complexity and duration of surgery, post-operative complications, postoperative days of hospital stay and pain evaluation on days 0, 1, 3 and 5 post-surgery. We studied the appropriateness of analgesic therapy in terms of incidence and prevalence of post-operative pain; we also related pain to patient characteristics, disease and surgical treatment to determine possible predictive factors. The population studied received adequate pain control through analgesic therapy immediately post-surgery and in the following days. No associations between gender, age and post-operative pain were found, whereas pathological cancer stage, complexity of surgery and tumour site were significantly associated with the risk of post-operative pain. Adequate pain control is essential in oncological patients, and particularly in head and neck cancer patients as the prevalence of pain in this localisation is reported to be higher than in other anatomical sites. Improved comprehension of the biological and psychological factors that characterise pain perception will help to

  9. Post-traumatic disorder symptoms and blunted diurnal cortisol production in partners of prostate cancer patients.

    Science.gov (United States)

    Thomas, Kamala S; Bower, Julienne E; Williamson, Timothy J; Hoyt, Michael A; Wellisch, David; Stanton, Annette L; Irwin, Michael

    2012-08-01

    Prostate cancer (PC) is the most common cancer diagnosed in men, and research suggests that coping with this illness can cause significant distress in patients as well as their partners. This study examined the relationship of caregiving for a partner with PC with diurnal cortisol output in women between the ages of 42 and 75 years old. Participants were women whose partners had PC (n = 19) and women who were in relationships with men with no diagnosed medical illness (n = 26). Women provided saliva samples (4 times per day over 3 days) in their natural environment. The Structured Clinical Interview for DSM-IV Axis-I Disorders was also conducted to assess for the presence of post-traumatic stress disorder (PTSD) and major depression. Partners of men with PC had lower daily cortisol output across the three days than controls, F(1,444.08) = 20.72, pcaregiver status, women who reported at least sub-threshold PTSD symptoms had lower cortisol production than those with no PTSD symptoms. Major depression did not explain differences in cortisol production between partners of PC patients and controls. Although these findings are preliminary, they highlight the importance of developing interventions aimed at reducing risk of psychopathology in partners of men with PC.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shih-Chieh [Department of Internal Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan (China); Chang, Cheng-Yu [Department of Chest Medicine, Far Eastern Memorial Hospital, Taipei 220, Taiwan (China); Shih, Jin-Yuan, E-mail: jyshih@ntu.edu.tw [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

    2011-06-10

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

  11. Post-synthetic regulation of HS structure: the yin and yang of the Sulfs in Cancer

    Directory of Open Access Journals (Sweden)

    Romain R Vives

    2014-01-01

    Full Text Available Heparan sulfate (HS is a complex polysaccharide that takes part in most major cellular processes, through its ability to bind and modulate a very large array of proteins. These interactions involve saccharide domains of specific sulfation pattern (S-domains, the assembly of which is tightly orchestrated by a highly regulated biosynthesis machinery. Another level of structural control does also take place at the cell surface, where degrading enzymes further modify HS post-synthetically. Amongst them are the Sulfs, a family of extracellular sulfatases (two isoforms in human that catalyze the specific 6-O-desulfation of HS. By targeting HS functional sulfated domains, Sulfs dramatically alter its ligand binding properties, thereby modulating a broad range of signaling pathways. Consequently, Sulfs play major roles during development, as well as in tissue homeostasis and repair. Sulfs have also been associated with many pathologies including cancer, but despite increasing interest, the role of Sulfs in tumor development still remains unclear. Studies have been hindered by a poor understanding of the Sulf enzymatic activities and conflicting data have shown either anti-oncogenic or tumor-promoting effects of these enzymes, depending on the tumor models analyzed. These opposite effects clearly illustrate the fine tuning of HS functions by the Sulfs, and the need to clarify the mechanisms involved. In this review, we will detail the present knowledge on the structural and functional properties of the Sulfs, with a special focus on their implication during tumor progression. Finally, we will discuss attempts and perspectives of using the Sulfs as a biomarker of cancer prognosis and diagnostic and as a target for anti-cancer therapies.

  12. Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer.

    Science.gov (United States)

    Yang, Jun; Ambrosone, Christine B; Hong, Chi-Chen; Ahn, Jiyoung; Rodriguez, Carmen; Thun, Michael J; Calle, Eugenia E

    2007-06-01

    NOS3 and MPO genes encode endothelial nitric oxide synthase and myeloperoxidase (MPO), respectively, which generate nitric oxide and reactive oxygen species. Because cigarette smoking generates reactive species, we hypothesized that NOS3 and MPO polymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations between NOS3 Glu298Asp and MPO G-463A polymorphisms and breast cancer risk by cigarette smoking among post-menopausal women in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Included in this analysis were 502 women who provided blood samples and were diagnosed with breast cancer between 1992 and 2001 and 505 cancer-free controls who were matched to the cases by age, race/ethnicity and date of blood donation. Genotyping for NOS3 and MPO was performed using TaqMan, and unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). No statistically significant relationships were found between NOS3 and MPO genotypes and breast cancer risk. When considering smoking, variant NOS3 genotypes (GT and TT) were significantly associated with reduced breast cancer risk among never smokers (OR = 0.67, 95% CI = 0.45-0.99), but were associated with higher risk among ever smokers (OR = 1.59, 95% CI = 1.05-2.41) and 2-fold increase in risk for those who smoked >10 cigarettes per day (OR = 2.19, 95% CI = 1.21-3.97). NOS3 genotypes appeared to be associated with risk of post-menopausal breast cancer among smokers, supporting the hypothesis that subgroups of women based upon genetic profiles may be at higher risk of breast cancer when exposed to tobacco smoke.

  13. Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.

    Science.gov (United States)

    Milagre, Carla S; Gopinathan, Ganga; Everitt, Gemma; Thompson, Richard G; Kulbe, Hagen; Zhong, Haihong; Hollingsworth, Robert E; Grose, Richard; Bowtell, David D L; Hochhauser, Daniel; Balkwill, Frances R

    2015-04-01

    Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.

  14. Putative relationship between hormonal status and serum pyrrolidone carboxypeptidase activity in pre- and post- menopausal women with breast cancer.

    Science.gov (United States)

    Carrera-González, María del Pilar; Ramírez-Expósito, María Jesús; Dueñas, Basilio; Martínez-Ferrol, Julia; Mayas, María Dolores; Martínez-Martos, José Manuel

    2012-12-01

    In breast cancer, hormonal changes are rather constant in post-menopausal women since they tend to vary only over long time spans. However, in pre-menopausal women, the development of breast cancer is associated with hormonal physiological variations. The aim of the present work was to analyse the changes in circulating levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pre- and post-menopausal women that were healthy or with breast cancer, and their connection to serum pyrrolidone carboxypeptidase (Pcp) activity. We observed significant changes in the hormonal profile in post-menopausal women with breast cancer compared to the control group. In pre-menopausal women, we found significant changes in circulating GnRH levels with respect to the healthy group. Our present results support the existence of neuroendocrine misregulation that could be involved in tumour progression, with Pcp being a potentially new pharmacological target in breast cancer treatments.

  15. Lack of survival benefit of post-operative radiation therapy in prostate cancer patients with positive lymph nodes.

    Science.gov (United States)

    Johnstone, P A S; Assikis, V; Goodman, M; Ward, K C; Riffenburgh, R H; Master, V

    2007-01-01

    Randomized data from SWOG 8794 and EORTC 22911 confirm the benefit of post-operative radiation therapy (RT) for selected patients with pT3 prostate cancer (CaP) after radical prostatectomy (RP). However, data regarding the potential benefit of RT for patients post-RP with positive lymph node (+LN) involvement are limited. We analyzed the Surveillance Epidemiology End Results (SEER) registry for population-based data on efficacy of post-operative RT for +LN patients after RP. As LN data have only been captured by SEER since 1988, we analyzed data for 1988-1992, with specific attention to 10-year relative survival (defined as observed survival divided by the survival of a gender-, age- and race-matched population cohort without disease). Specifically analyzed were data for 1921 patients with nonmetastatic prostate cancer who underwent surgery alone, or surgery followed by RT, and who had +LNs documented. SEER does not code the interval between surgery and RT, so the ratio of patients receiving salvage versus adjuvant therapy is unknown. Using follow-up data through 2002, post-diagnosis survival was examined by number of +LNs. There was no significant relative survival benefit for +LN patients receiving post-operative RT (chi(2)P=0.270). These data do not support routine use of post-operative RT for patients with +LNs in the surgical specimen.

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

    Directory of Open Access Journals (Sweden)

    Lee Joo

    2012-03-01

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

  17. Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmo Diet and Cancer Cohort.

    Directory of Open Access Journals (Sweden)

    Joana A Dias

    Full Text Available Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association.In the Malmö Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55-73 years at baseline (1991-96; 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010. In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling we examined systemic inflammation markers: oxidized (ox-LDL, interleukin (IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR and 95% confidence intervals (CI for breast cancer risk was calculated using multivariable conditional logistic regression.Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI: 0.65 (0.47-0.90, 0.63 (0.45-0.89 respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43-0.99, p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05-2.79, p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer.Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.

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

    Science.gov (United States)

    Kola Srinivas, Navya Sree; Verma, Ruchi; Pai Kulyadi, Girish; Kumar, Lalit

    2017-01-01

    Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit® RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation. To study the effect of CMAs and CPPs, 23 full factorial design was applied. The particle size, polydispersity index, and zeta potential of the optimized solution were 248.20 nm, 0.391, and −5.62 mV, respectively. Drug content of the optimized nanoformulation was found to be 87.74%±1.19%. Atomic force microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are smooth and spherical in nature. In vitro cytotoxicity studies of the nanosuspension on Vero cell line revealed that the formulation is nontoxic. The gefitinib nanosuspension released 60.03%±4.09% drug over a period of 84 h, whereas standard drug dispersion released only 10.39%±3.37% drug in the same duration. From the pharmacokinetic studies, half-life, Cmax, and Tmax of the drug of an optimized nanosuspension were found to be 8.65±1.99 h, 46,211.04±5,805.97 ng/mL, and 6.67±1.77 h, respectively. A 1.812-fold increase in relative bioavailability of nanosuspension was found, which confirmed that the present formulation is suitable to enhance the oral bioavailability of gefitinib. PMID:28031710

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

    Science.gov (United States)

    Kola Srinivas, Navya Sree; Verma, Ruchi; Pai Kulyadi, Girish; Kumar, Lalit

    Gefitinib is an anticancer agent which acts by inhibiting epidermal growth factor receptor tyrosine kinase receptors. The aim of the present study was to prepare gefitinib nanosuspension. Gefitinib was encapsulated in Eudragit(®) RL100 and then dispersed in stabilizer solution, polyvinyl alcohol, and polyvinylpyrrolidone K30. Nanosuspension was prepared by using homogenization and ultrasonication techniques. The quality by design approach was also used in the study to understand the effect of critical material attributes (CMAs) and critical processing parameters (CPPs) on critical quality attributes and to improve the quality and safety of formulation. To study the effect of CMAs and CPPs, 2(3) full factorial design was applied. The particle size, polydispersity index, and zeta potential of the optimized solution were 248.20 nm, 0.391, and -5.62 mV, respectively. Drug content of the optimized nanoformulation was found to be 87.74%±1.19%. Atomic force microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are smooth and spherical in nature. In vitro cytotoxicity studies of the nanosuspension on Vero cell line revealed that the formulation is nontoxic. The gefitinib nanosuspension released 60.03%±4.09% drug over a period of 84 h, whereas standard drug dispersion released only 10.39%±3.37% drug in the same duration. From the pharmacokinetic studies, half-life, Cmax, and Tmax of the drug of an optimized nanosuspension were found to be 8.65±1.99 h, 46,211.04±5,805.97 ng/mL, and 6.67±1.77 h, respectively. A 1.812-fold increase in relative bioavailability of nanosuspension was found, which confirmed that the present formulation is suitable to enhance the oral bioavailability of gefitinib.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    AIM: To determine swallowing outcomes and hyolaryngeal mechanics associated with post radiation therapy head and neck cancer(rt HNC) patients using videofluoroscopic swallow studies. METHODS: In this retrospective cohort study, video-fluoroscopic images of rt HNC 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.RESULTS: The rt HNC group was characterized by poor swallowing outcomes compared to the control group in regards to: Penetration-aspiration scale(P < 0.0001), normalized residue ratio scale(NRRS) for the valleculae(P = 0.002) and NRRS for the piriform sinuses(P = 0.003). Timing and distance measurements of the anterior muscular sling were not significantly different in the two groups, whereas for the PMS time of displacement was abbreviated(P = 0.002) and distance of excursion was reduced(P = 0.02) in the rt HNC group. A canonical variate analysis shows a significant reduction in pharyngeal mechanics in the rt HNC group(P < 0.0001). The PCR was significantly higher in the test group than the control group(P = 0.0001) indicating reduced efficiency in pharyngeal clearance. CONCLUSION: Using videofluoroscopy, this study shows rt HNC

  1. 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

    The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation...... and isomerization. Each PTM results from a specific local physiological or pathobiological process. Identification of each modification to a tissue-specific protein may reveal a unique disease-specific biochemical marker. During cancer metastasis, the host tissue is extensively degraded and replaced by cancer...

  2. 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

    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......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...... 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...

  3. The Epidermal Growth Factor Receptor (EGFR) Inhibitor Gefitinib Reduces but Does Not Prevent Tumorigenesis in Chemical and Hormonal Induced Hepatocarcinogenesis Rat Models

    OpenAIRE

    Silvia Ribback; Verena Sailer; Enrico Böhning; Julia Günther; Jaqueline Merz; Frauke Steinmüller; Kirsten Utpatel; Antonio Cigliano; Kristin Peters; Pilo, Maria G.; Matthias Evert; Calvisi, Diego F.; Frank Dombrowski

    2016-01-01

    Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N-Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thy...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  5. EGF receptor inhibitors increase ErbB3 mRNA and protein levels in breast cancer cells

    DEFF Research Database (Denmark)

    Grøvdal, Lene Melsæther; Kim, Jiyoung; Holst, Mikkel Roland;

    2012-01-01

    that, when inhibiting the epidermal growth factor receptor (EGFR) with the tyrosine kinase inhibitor gefitinib, increased activation of ErbB3 via MET, or by re-localization of ErbB3 mediates cell survival. Here we show further evidence that members of the ErbB receptor family facilitate resistance......The potential benefits of drugs directly targeting the ErbB receptors for cancer therapy have led to an extensive development within this field. However, the clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited due to a high frequency of resistance. It has been reported...... to EGFR inhibitor treatment in ErbB2 overexpressing breast cancer cells. We found that gefitinib treatment increased ErbB3 expression, both at protein and mRNA levels. ErbB3 expression was upregulated not only by gefitinib but also by a panel of different EGFR inhibitors, suggesting that inhibition...

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    V Anuradha

    2013-01-01

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

  8. Transcriptional and post-translational regulation of Bim controls apoptosis in melatonin-treated human renal cancer Caki cells.

    Science.gov (United States)

    Park, Eun Jung; Woo, Seon Min; Min, Kyoung-Jin; Kwon, Taeg Kyu

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) has recently gained attention as an anticancer agent and for combined cancer therapy. In this study, we investigated the underlying molecular mechanisms of the effects of melatonin on cancer cell death. Treatment with melatonin induced apoptosis and upregulated the expression of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim) in renal cancer Caki cells. Furthermore, downregulation of Bim expression by siRNA markedly reduced melatonin-mediated apoptosis. Melatonin increased Bim mRNA expression through the induction of Sp1 and E2F1 expression and transcriptional activity. We found that melatonin also modulated Bim protein stability through the inhibition of proteasome activity. However, melatonin-induced Bim upregulation was independent of melatonin's antioxidant properties and the melatonin receptor. Taken together, our results suggest that melatonin induces apoptosis through the upregulation of Bim expression at the transcriptional level and at the post-translational level.

  9. 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.

  10. EGFR基因突变与EGFR酪氨酸激酶抑制剂近期疗效的关系%Relationship between mutations of epidermal growth factor receptor in the plasma and pleural effusion and responses to gefitinib in advanced pretreated non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郭健; 周彩存; 张颉; 唐亮

    2007-01-01

    背景与目的 多项研究证实表皮生长因子受体(epidermal growth factor receptor,EGFR)突变与EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的疗效存在相关性.本研究应用荧光定量PCR技术检测晚期肺癌的EGFR基因突变,分析其与EGFR TKI药物Gefitinib二线治疗晚期非小细胞肺癌(nonsmall cell lung cancer,NSCLC)的近期疗效之间的关系.方法 从63例血浆和胸腔积液标本(其中血浆53例,胸腔积液10例)中提取游离DNA,应用荧光定量PCR技术进行EGFR 18、19、21外显子基因的检测,并结合临床进行分析.结果 在63例血浆和胸腔积液标本中检测到EGFR基因突变17例,突变率为27.0%.EGFR基因突变主要见于女性及非吸烟人群(P<0.05).存在EGFR基因突变的患者Gefitinib二线治疗的疗效明显优于野生型患者(P<0.01).结论 晚期NSCLC患者的血浆、胸腔积液游离DNA中存在EGFR基因突变,这类突变可以通过荧光定量PCR技术检测出来.EGFR基因突变患者对Gefitinib的反应率明显高于野生型患者,检测胸腔积液和/或血浆EGFR基因突变有助于选择有效患者接受EGFR TKI治疗.

  11. Predictive role of post-treatment [{sup 18}F]FDG PET/CT in patients with uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hoon Chung, Hyun, E-mail: chhkmj@gmail.com [Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Kim, Jae Weon, E-mail: chhkmj1@snu.ac.kr [Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Kang, Keon Wook, E-mail: kangkw@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Park, Noh-Hyun, E-mail: pnhkhr@snu.ac.kr [Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Song, Yong-Sang, E-mail: yssong@snu.ac.kr [Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Chung, June-Key, E-mail: jkchung@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Kang, Soon-Beom, E-mail: ksboo308@plaza.snu.ac.kr [Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of)

    2012-08-15

    Objective: To evaluate the efficacy of post-treatment positron emission tomography (PET)/computed tomography (CT) for identification of tumor recurrence, and to determine whether [{sup 18}F]fluorodeoxyglucose (FDG) uptake measured as the maximum standardized uptake value (SUV{sub max}) has predictive role regarding survival in patients with uterine cervical cancer. Methods: Medical records from 276 women with uterine cervical cancer who had post-treatment [{sup 18}F]FDG PET/CT performed were retrospectively reviewed. Results of PET/CT scans were compared with histological or clinical examination. Results: Ninety-five (34.4%) of the 276 patients had documented recurrence by either surgical biopsy or clinical and imaging follow-up. Median duration from treatment to PET/CT scan was 24 months (range, 6-307). The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-treatment PET/CT were 94.7%, 87.8%, 80.4%, 97%, and 90.2%, respectively. The PET/CT scan modified both the diagnostic or treatment plan in 67 patients (24.3%). Patients were divided into two groups according to cut-off SUV{sub max} established on the basis of ROC analysis (<5.25 vs. {>=}5.25), and there was a significant difference in OS between groups (p = 0.001). In addition, the 5-year progression-free survival (PFS) and OS rates of patients with a negative PET/CT scan for recurrence were significantly better than those with a positive PET/CT (98.62% vs. 17.83%, p < 0.0001 for PFS, 99.31% vs. 85.38%, p = 0.0015 for OS). Conclusion: Post-treatment PET/CT scan is a sensitive and accurate surveillance modality, and provides prognostic information in uterine cervical cancer. Furthermore, it may allow individualization of patient care.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-10

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

  13. Understanding barriers to exercise implementation 5-year post-breast cancer diagnosis: a large-scale qualitative study.

    Science.gov (United States)

    Hefferon, Kate; Murphy, Helen; McLeod, Janice; Mutrie, Nanette; Campbell, Anna

    2013-10-01

    Due to the amount of literature supporting exercise participation after cancer diagnosis, there has been recent interest in barriers to exercise engagement among cancer patients. However, little is known regarding reasons why people choose to disengage and how this disengagement occurs over time. This study aimed to qualitatively study the perceived barriers to exercise implementation, 5-year post-breast cancer diagnosis. Eighty-three female breast cancer survivors participated in a one-to-one semi-structured interview, regarding their experience of exercise over the past 5 years following their original participation in a group-based structured exercise intervention after diagnosis (41 from intervention and 42 from original control group). The data were analysed using inductive thematic analysis. The findings included three main themes and several subthemes regarding the women's perceived barriers: psychological barriers (lack of motivation, fears, dislike of gym, not being the 'sporty type'), physical barriers (the ageing process, cancer treatment and other physical co-morbidities, fatigue and weight gain) and contextual and environmental barriers (employment, traditional female care-giving roles, proximity/access to facilities, seasonal weather). The findings add inductive support to the current survivor health research advocating the use of activity immediately after diagnosis, as well as the need for tailored activity programmes in order to overcome potential obstacles.

  14. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  15. 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.

  16. Myc post-transcriptionally induces HIF1 protein and target gene expression in normal and cancer cells

    Science.gov (United States)

    Doe, Megan R.; Ascano, Janice; Kaur, Mandeep; Cole, Michael D.

    2012-01-01

    c-Myc is frequently overexpressed in tumors and plays an important role in the regulation of cancer metabolism. Hypoxia-inducible factor-1 (HIF1), the master regulator of the hypoxic response, enhances tumorigenesis and influences metabolism via upregulation of the glycolytic pathway and suppression of mitochondrial respiration. Together, deregulated Myc and HIF1 cooperate to lend metabolic advantages to proliferating cancer cells and contribute to the Warburg Effect. Here we show that overexpression of Myc significantly stabilizes the alpha subunit of HIF1 (HIF1alpha) under normoxic conditions and enhances HIF1alpha accumulation under hypoxic conditions in cells. Post-transcriptional regulation of HIF1α by Myc led to the induction of HIF1α gene targets. Normoxic HIF1α protein expression was also dependent on Myc. Functionally; HIF1α expression was required for Myc-induced anchorage-independent growth and cell proliferation. Myc-dependent stabilization of HIF1α involved either disruption of binding to the VHL complex or post-translational protein modifications. Taken together, our findings uncover a previously uncharacterized regulatory relationship between Myc and HIF1 that has important implications for cancer metabolism and development. PMID:22186139

  17. 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.

  18. Interferon-alpha in combination with either imatinib (Gleevec) or gefitinib (Iressa) in metastatic renal cell carcinoma: a phase II trial.

    Science.gov (United States)

    Amato, Robert J; Jac, Jaroslaw; Hernandez-McClain, Joan

    2008-06-01

    Treatments for metastatic renal cell carcinoma (MRCC) are limited. RCCs frequently overexpress epithelial growth factor receptor and express c-Kit and platelet-derived growth factor receptor-beta. Combination of interferon with tyrosine kinase inhibitors of epithelial growth factor receptor [gefitinib (Iressa)] or c-Kit and platelet-derived growth factor receptor-beta [imatinib (Gleevec)] was evaluated for efficacy and safety. Patients with MRCC received 12-week cycles of interferon [3 million units (MU) subcutaneously thrice in week 1 and 6 MU thrice weekly thereafter] and either gefitinib (500 mg daily) or imatinib (600 mg daily). The gefitinib/imatinib dose was reduced as needed owing to toxicity. The primary endpoint was objective tumor response. Secondary endpoints were time to tumor progression, overall survival, and safety. Seventeen patients were enrolled. Most had clear cell [36% (6/17)] or papillary [36% (6/17)] tumors. Most (n=14) were treated on the gefitinib arm, including two patients who crossed over from the imatinib arm after experiencing disease progression. Objective tumor responses were evaluable in 14 patients (82%). Of these 14, partial responses occurred in three (21%), stable disease in seven (50%), and progressive disease in four (29%). The most frequent treatment-related adverse events were skin rash, flu-like symptoms, and fatigue (both treatment arms); diarrhea (gefitinib arm only); and thrombocytopenia and leukopenia (imatinib arm only). Median time to tumor progression (range) for patients on the gefitinib arm only was 4.27 (1.13-15.97) months and median overall survival (range) was 11.42+ (1.13-29.07+) months. Combination of gefitinib with interferon safely delays progression of refractory MRCC. Further studies in this setting are warranted.

  19. 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.

  20. Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer.

    Science.gov (United States)

    Bagó, Juli R; Pegna, Guillaume J; Okolie, Onyi; Hingtgen, Shawn D

    2016-04-01

    Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  2. Associations of self-rated health and socioeconomic status with information seeking and avoiding behavior among post- treatment cancer patients.

    Science.gov (United States)

    Jung, Minsoo

    2014-01-01

    This study investigated how self-rated health and socioeconomic status are associated with behaviour of cancer survivors regarding desire for information. For this association, we compared survivors who did not seek information about cancer with those who did. We examined how sociodemographic, socioeconomic, cancer- related, and health information factors are associated with self-rated health (SRH) by health information seeking/ avoiding behavior in a survey of 502 post-treatment cancer patients. In the information seeking group, all four factors exhibited significant relationships with SRH. SRH values were significantly high for women (pinformation by themselves (pinformation avoiding group, not only were there no significant relationships between socioeconomic status (SES) and SRH, but there were negative associations between their attitude/capacity and the SRH. In terms of communication equity, the promotion of information seeking behavior can be an effective way to reduce health disparities that are caused by social inequalities. Information avoiding behavior, however, does not exhibit a negative contribution toward the relationship between SRH and SES. Information seeking behavior was positively associated with SRH, but avoiding behavior was not negatively associated. We thus need to eliminate communication inequalities using health intervention to support information seeking behavior, while simultaneously providing support for avoiders.

  3. A new hospice consulting system for terminal cancer patients in transferring to post-acute care options in Taiwan.

    Science.gov (United States)

    Chang, P M-H; Liu, Y-Y L; Chao, T-C; Lin, H-L; Chen, M-B; Chen, P-M; Chiou, T-J

    2010-03-01

    The terminal cancer patients increase needs for hospice care day by day. A new hospice consulting system has been developed in Taiwan to provide options for terminal cancer patients in choosing a suitable post-acute hospice care while a combined hospice care system is also given by the consulting team in the acute wards. Hereinafter is our report. From March 2005 to January 2006, 313 terminal cancer patients were analysed. These patients had signed consent forms for palliative treatment and had received consultations from the new hospice consulting system. Multivariate analysis showed that the home care patients had better performance status (P = 0.012), less shortness of breath (P = 0.006), less limbs swelling (P = 0.043), less flatulency (P = 0.000) and less constipation (P = 0.018). Among the 162 patients with regular follow-up, the symptoms/signs were significantly improved after intervention of consulting team in pain (P = 0.000), shortness of breath (P = 0.000), difficulty in sleeping (P = 0.002), nausea (P = 0.004), constipation (P = 0.008), changes in skin (P = 0.024) and adoption (P = 0.000). This new system had significant improvement in the terminal cancer patients' symptoms/signs control in acute wards and could contribute to the care quality of home care patients.

  4. 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

  5. Identification of Post-Transcriptional Modulators of Breast Cancer Transcription Factor Activity Using MINDy

    Science.gov (United States)

    Campbell, Thomas M.; Castro, Mauro A. A.; Ponder, Bruce A. J.

    2016-01-01

    We have recently identified transcription factors (TFs) that are key drivers of breast cancer risk. To better understand the pathways or sub-networks in which these TFs mediate their function we sought to identify upstream modulators of their activity. We applied the MINDy (Modulator Inference by Network Dynamics) algorithm to four TFs (ESR1, FOXA1, GATA3 and SPDEF) that are key drivers of estrogen receptor-positive (ER+) breast cancer risk, as well as cancer progression. Our computational analysis identified over 500 potential modulators. We assayed 189 of these and identified 55 genes with functional characteristics that were consistent with a role as TF modulators. In the future, the identified modulators may be tested as potential therapeutic targets, able to alter the activity of TFs that are critical in the development of breast cancer. PMID:27997592

  6. Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short Report

    OpenAIRE

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

    2015-01-01

    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 les...

  7. FDA Approves Test to Aid Post-PSA Biopsy Decisions | Division of Cancer Prevention

    Science.gov (United States)

    The Food and Drug Administration (FDA) has approved a test to help men with elevated prostate-specific antigen (PSA) test scores decide whether to have a biopsy to test for prostate cancer. The Access Hybritech p2PSA test is approved for use in men aged 50 or older who have a PSA test score between 4 and 10 ng/ml but who show no signs of cancer during a digital rectal exam. |

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

    Science.gov (United States)

    2003-03-01

    molecular biomarkers. Patients will continue to be followed for any clinical recurrences or toxicity as part of their usual cancer care . BODY: WORK DONE...survival rates, breast cancer results in considerable morbidity and patient care costs. Chemoprevention is an important aspect of curbing the progression...feedback mlechan kmi to regul te the estrogen- induced proliferation of the manim mary tissueC. Some1 researchers have postulated a~n interactinn or VDIR

  9. Human papilloma viruses and cancer in the post-vaccine era.

    Science.gov (United States)

    Galani, E; Christodoulou, C

    2009-11-01

    Human papilloma viruses (HPV) are strong human carcinogens, in fact today they are considered as the second most frequent carcinogen. In the middle of the 1970s the hypothesis that cervical cancer may arise from viruses was established and in the 1990s the relationship between HPV and cervical neoplasia was confirmed. HPV infections are the most common sexually transmitted infections. Specific subtypes of human papilomaviruses are now considered as the etiological agents in nearly all cases of cervical cancer and cervical epithelial neoplasia. Approximately 470,000 new cases and 23,000 deaths of cervical cancer occur each year, with the majority taking place in developing countries. Cervical cancer remains among the three leading causes of cancer deaths among women below the age of 45. Human papilomaviruses are classified into two groups: high-risk (oncogenic) types and low risk types. HPV types 16, 18, 45 and 31 are considered to be the most important oncogenic types. Subtypes 16 and 18 are the causative agents of more than 50% of cervical pre-cancerous lesions, and more than 70% of cervical cancer cases. High risk subtypes are also implicated with anal, perianal and oropharyngeal carcinomas. Recently, the prophylactic bivalent HPV 16/18 and the quadrivalent HPV 6/11/16/18/ vaccines have been approved. The development of prophylactic vaccines against human papilomavirus has been hailed as one of the most significant advances of recent years and it is expected to reduce dramatically the mortality of human papilomavirus associated cancers, but has also given rise to some of the most intense scientific debates.

  10. 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.

  11. 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.

  12. Selenium and vitamin E for prostate cancer: post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) status.

    Science.gov (United States)

    Ledesma, Mark C; Jung-Hynes, Brittney; Schmit, Travis L; Kumar, Raj; Mukhtar, Hasan; Ahmad, Nihal

    2011-01-01

    Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations.

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

    Institute of Scientific and Technical Information of China (English)

    于庆生; 王炜; 汪小明; 王汉明; 帅剑峰

    2002-01-01

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

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

    Science.gov (United States)

    Tiwari, Pallavi; Danish, Shabbar; Madabhushi, Anant

    2014-03-01

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

  15. Combination of Resveratrol and Zinc for Prostate Cancer Management

    Science.gov (United States)

    2013-05-01

    hellebore) in 1940 (re- viewed in Timmers et al.).11 In 1963, he extracted resveratrol from the roots of the plant Polygonum cuspidatum (Japanese...plant extracts 41 Geneistin SV-40 rat model of prostate cancer Combination reduced the most severe grade of prostate cancer in SV-40 Tag-targeted...found to overcome chemoresistance by inducing cell cycle disruption and apoptosis 46 Quercitin + Catechin + Gefitinib Nude mouse model of mammary

  16. A prospective cohort study of the combined effects of physical activity and anthropometric measures on the risk of post-menopausal breast cancer.

    Science.gov (United States)

    Bellocco, Rino; Marrone, Gaetano; Ye, Weimin; Nyrén, Olof; Adami, Hans-Olov; Mariosa, Daniela; Lagerros, Ylva Trolle

    2016-04-01

    Although keeping a healthy weight and being physically active are among the few modifiable risk factors for post-menopausal breast cancer, the possible interaction between these two risk factors remains to be established. We analyzed prospectively a cohort of 19,196 women who provided detailed self-report on anthropometric measures, physical activity and possible confounders at enrollment in 1997. We achieved complete follow-up through 2010 and ascertained 609 incident cases of post-menopausal invasive breast cancer. We calculated metabolic energy turnover (MET h/day) per day and fitted Cox proportional hazards models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs). The incidence of post-menopausal breast cancer among obese women (BMI ≥ 30 kg/m(2)) was 58 % higher (HR 1.58, CI 1.16-2.16) than in women of normal weight (18.5 ≤ BMI day) had 40 % higher incidence of post-menopausal breast cancer (HR 1.40, CI 1.11-1.75) than those in the highest tertile (≥ 38.2 MET h/day). The excess incidence linked to these two factors seemed to combine in an approximately additive manner; the incidence among the most obese and sedentary women was doubled (HR 2.07, CI 1.31-3.25) compared with the most physically active women with normal weight. No heterogeneity of the physical activity-linked risk ratios across strata of BMI was detected (p value for interaction = 0.98). This prospective study revealed dose-dependent, homogenous inverse associations between post-menopausal breast cancer incidence and physical activity across all strata of BMI, and between post-menopausal breast cancer incidence and BMI across all strata of physical activity, with no evidence of additive or multiplicative interaction between the two, suggesting independent effects.

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

    Directory of Open Access Journals (Sweden)

    Sophie Pinel

    Full Text Available In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment "gefitinib + radiotherapy" and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4 harboring high levels of phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF 75 mg/kg/day x 5 days/week, for 2 weeks and/or fractionated radiotherapy (RT: 5x2Gy/week for 2 weeks. Our results showed that GEF and/or RT induced significant tumor growth delays. However, only the TCG3 xenografts were highly responsive to the combination GEF+RT, with ∼50% of tumor cure. Phosphoproteins analysis five days after treatment onset demonstrated in TCG3 xenografts, but not in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a transient beneficial therapeutic response, rapidly followed by tumor regrowth, along with a major vascular remodeling. Taken together, our data evoked an "EGFR-addictive" behavior for TCG3 tumors. This study confirms that combination of gefitinib with fractionated irradiation could be a potent therapeutic strategy for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment seems mainly beneficial for "EGFR-addictive" tumors. Unfortunately, neither the usual molecular markers (EGFR amplification, PTEN loss nor the basal overexpression of phosphoproteins were useful to distinguish this responsive tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the treatment might be more relevant, and requires further validation.

  18. A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to post-menopausal breast and colorectal cancer risk

    Science.gov (United States)

    Elands, Rachel J. J.; Simons, Colinda C. J. M.; Riemenschneider, Mona; Isaacs, Aaron; Schouten, Leo J.; Verhage, Bas A.; Van Steen, Kristel; Godschalk, Roger W. L.; van den Brandt, Piet A.; Stoll, Monika; Weijenberg, Matty P.

    2017-01-01

    Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC. PMID:28117334

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

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald

    2014-01-01

    design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis...... 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...

  20. Post-Doctoral Training Program in Bio-Behavioral Breast Cancer Research

    Science.gov (United States)

    2005-05-01

    Personality and Individual Differences , 35...Care Cancer, 10(5): 416-421. Kim Y, Seidlitz L (2002). Spirituality moderates the effect of stress on emotional and physical adjustment. Personality and Individual Differences , 32...2004). Spirituality and affect: A function of changes in religious affiliation. Personality and Individual Differences , 37: 861-870. Sheldon

  1. 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

    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...

  2. Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer.

    NARCIS (Netherlands)

    Spermon, J.R.; Ramos, L.; Wetzels, A.M.M.; Sweep, C.G.J.; Braat, D.D.M.; Kiemeney, L.A.L.M.; Witjes, J.A.

    2006-01-01

    BACKGROUND: While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood. METHODS: Semen and seru

  3. A pooled analysis of post-diagnosis lifestyle factors in association with late estrogen-receptor-positive breast cancer prognosis.

    Science.gov (United States)

    Nechuta, Sarah; Chen, Wendy Y; Cai, Hui; Poole, Elizabeth M; Kwan, Marilyn L; Flatt, Shirley W; Patterson, Ruth E; Pierce, John P; Caan, Bette J; Ou Shu, Xiao

    2016-05-01

    Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ Stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre- to post-diagnosis weight change, body mass index (BMI) (kg/m(2)), recreational physical activity, alcohol intake and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q-statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ≥ 10% weight gain and obesity (BMI, 30-34.99 and ≥ 35) were associated with increased risk of late recurrence (hazard ratios (95% confidence intervals): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). Physical activity was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9 to factors were associated with late outcomes among long-term ER+ breast cancer survivors.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  5. Post-marketing Safety Evaluation of S-1 in Patients with Inoperable or Recurrent Breast Cancer: Especially in Patients Treated with S-1 + Trastuzumab

    OpenAIRE

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-01-01

    Objective The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. Methods A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Resu...

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

    Science.gov (United States)

    Holland, Fiona; Archer, Stephanie; Montague, Jane

    2016-08-01

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

  7. 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.

  8. Effectiveness and safety of post-induction phase bevacizumab treatment for patients with non-small-cell lung cancer: results from the ARIES observational cohort study.

    Science.gov (United States)

    Kosty, Michael P; Wozniak, Antoinette J; Jahanzeb, Mohammad; Leon, Larry; Fish, Susan; Hazard, Sebastien J; Lynch, Thomas J

    2015-12-01

    Data from randomized, controlled trials suggest that post-induction phase (IP) treatment with bevacizumab may benefit patients with advanced non-small-cell lung cancer (NSCLC). Real-world clinical practice, however, can involve variable use and patterns of treatment in broader patient populations. To assess the effect of bevacizumab on post-IP overall survival (OS) following IP chemotherapy + bevacizumab, analyses were conducted in patients enrolled in the Avastin(®) Registry--Investigation of Effectiveness and Safety (ARIES) observational cohort study (OCS) who received post-IP bevacizumab. ARIES was a large, prospective OCS of patients who received chemotherapy in combination with bevacizumab for the first-line treatment of NSCLC. This unplanned, post hoc analysis included patients who received chemotherapy and bevacizumab and who did not have progressive disease through the completion of IP treatment. A dichotomous analysis compared outcomes in patients who did and did not receive bevacizumab before a landmark date of day 30 post IP. A cumulative exposure analysis used a time-dependent Cox regression model to assess the effect of cumulative post-IP bevacizumab exposure on post-IP OS. In the dichotomous analysis, the duration of post-IP OS was significantly longer in patients who received post-IP bevacizumab; median post-IP OS was 15.6 vs. 11.3 months, respectively (hazard ratio [HR] = 0.80; 95 % confidence interval 0.71-0.91; P post-IP OS by 2.7 %, on average. In conclusion, post-IP bevacizumab exposure was associated with improved post-IP OS in patients with advanced NSCLC who were enrolled in the ARIES OCS.

  9. Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up.

    Science.gov (United States)

    Manikantan, Kapila; Khode, Shailesh; Dwivedi, Raghav C; Palav, Rajan; Nutting, Chris M; Rhys-Evans, Peter; Harrington, Kevin J; Kazi, Rehan

    2009-12-01

    Follow-up in patients treated for head and neck cancer (HNC) is aimed at early detection of recurrence, metastases and second primary tumours. Various modalities for the routine follow-up of patients with HNC have been proposed and studied in the literature. Consequently, practising head and neck surgeons and oncologists all over the world use different guidelines and protocols to follow-up their patients. These guidelines involve follow-up intervals of varying intensity and schedule an assortment of investigations that may be neither logical nor practical. This follow-up process may be difficult to administrate, cause unnecessary discomfort and morbidity to the patient and can have serious cost-implications to the healthcare system. This review summarises strategies for follow-up, imaging modalities and key investigations in the literature published between 1980 and 2009. In this structured review, we have assessed studies in the literature that have addressed follow-up intervals, imaging tests, tumour markers, endoscopy and thyroid function tests as a part of the routine post-treatment surveillance in HNC patients. Studies analysing the cost benefit of such surveillance have also been addressed. Based on the evidence presented, we have compiled definitive recommendations for effective surveillance/post-treatment follow-up in patients with HNC.

  10. Post-mastectomy radiotherapy for one to three axillary node positive early breast cancer: To radiate or not to radiate?

    Directory of Open Access Journals (Sweden)

    Sayan Paul

    2013-01-01

    Full Text Available Post-mastectomy radiotherapy (PMRT in early breast cancer has long been a matter of debate among oncologists. The American Society of Clinical Oncology (ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO recommend the use of PMRT for patients, whose primary tumor is larger than 5 cm and/or patients who have four or more involved axillary lymph nodes (ALNs. Recently, few trials have been published showing the positive impact of PMRT on overall survival (OS even in patients having 1-3 positive ALNs with T1-T2 primary disease or early breast cancer (EBC. So, it has become a matter of controversy whether to radiate or not to radiate? We have made an extensive search in the internet in Pubmed and other sites of medical publication mentioning our topic of discussion and reviewed the relevant articles. We nearly got 3,220 articles. After reviewing the available publications in the internet, we blended the elixir with our experience and tried to find an answer of our question. In conclusion, PMRT significantly and substantially improved loco-regional control and overall survival in patients with 1-3 positive nodes as in patients with 4 or more positive nodes, and nearly the same number of patients is needed to treat to avoid a loco-regional recurrence and/or death in both groups. We should reconsider the current guidelines for the indication for PMRT.

  11. 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.

  12. Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in post-menopausal patients with breast cancer

    Science.gov (United States)

    Hertz, Daniel L.; Kidwell, Kelley M.; Seewald, Nicholas J.; Gersch, Christina L.; Desta, Zeruesenay; Flockhart, David A; Storniolo, Ana-Maria; Stearns, Vered; Skaar, Todd C; Hayes, Daniel F; Henry, N. Lynn; Rae, James M.

    2016-01-01

    Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 post-menopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected two hours after exemestane dosing at a 1 or 3 month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) SNP would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates. CYP3A4*22 was associated with a 54% increase in exemestane concentration (p<0.01). Concentration was greater in patients who reported White race, had elevated aminotransferases, renal insufficiency, lower body mass index, and had not received chemotherapy (all p<0.05), and CYP3A4*22 maintained significance after adjustment for covariates (p<0.01). These genetic and clinical predictors of exemestane concentration may be useful for treatment individualization in patients with breast cancer. PMID:27549341

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

    NARCIS (Netherlands)

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  16. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Franceschi, E; Cavallo, G; Lonardi, S; Magrini, E; Tosoni, A; Grosso, D; Scopece, L; Blatt, V; Urbini, B; Pession, A; Tallini, G; Crinò, L; Brandes, A A

    2007-04-10

    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.

  17. Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors.

    NARCIS (Netherlands)

    Giaccone, G.; Gonzalez-Larriba, JL; Oosterom, van A.T.; Alfonso, R; Smit, E.F.; Martens, M.; Peters, G.J.; Vijgh, van der WJ; Smith, R; Averbuch, S; Fandi, A

    2004-01-01

    BACKGROUND: The aim of this study was to investigate the tolerability, pharmacokinetic interaction and antitumor activity of gefitinib ("Iressa", ZD1839), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, combined with gemcitabine and cisplatin in chemotherapy-n

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-20

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

  19. 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.

  20. From cell signaling to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jin DING; Yun FENG; Hong-yang WANG

    2007-01-01

    Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood.Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key mol-ecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec),herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects.

  1. 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.

  2. 喉癌患者的术后护理%Post-operative care of patients with laryngeal cancer

    Institute of Scientific and Technical Information of China (English)

    苏日格

    2015-01-01

    作为头颈部最常见的恶性肿瘤,喉癌的发病率逐年上升。以手术为主放化疗为辅的综合治疗是喉癌的主要治疗方式。因此,患者在经历手术的创伤后,承受发声功能受损或丧失的痛苦,身体和心理遭遇巨大的打击。有效的术后护理不仅能提高康复效果还能帮助患者尽快摆脱手术造成的心理阴影。在“以患者为本”的现代医学模式下,将以精神疏导为重点的心理护理与有效技术护理,包括气道护理、营养护理、口腔护理、出院健康指导相结合的护理模式应成为喉癌术后护理工作的核心内容。%The incidence of laryngeal cancer, the most common cancer in head and neck, increases year by year. A comprehensive treatment based on surgery supplemented by radiotherapy and chemotherapy is the primary treatment for laryngeal cancer. Patients have to suffer with the trau-ma of surgery and experience the pain of vocal impairment or loss, which seriously impair their physical and mental health. Effective postoperative care will not only improve rehabilitation, but help patients get rid of the psychological shadow caused by surgery as soon as possible. With the de-velopment of the"patient-oriented" modern medical model, the core work of post-operative care of laryngeal cancer should be psychological care which focuses on spiritual counseling in combination with effective techniques care including airway care, nutritional care, oral care, and discharge health guidance.

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

    Institute of Scientific and Technical Information of China (English)

    施怀杰; 王爱玉

    2001-01-01

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

  4. 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

    2014-01-01

    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 T790M

  5. Breathing exercises improve post-operative pulmonary function and quality of life in patients with lung cancer: A meta-analysis.

    Science.gov (United States)

    Liu, Wei; Pan, Ying-Li; Gao, Cai-Xiang; Shang, Zuo; Ning, Li-Juan; Liu, Xing

    2013-04-01

    Previous research has shown that breathing exercises may improve the prognosis and health status in patients with lung cancer by enhancing pulmonary function and quality of life (QOL). However, individually published results are inconclusive. The aim of the present meta-analysis was to evaluate the clinical value of breathing exercises on post-operative pulmonary function and QOL in patients with lung cancer. A literature search of Pubmed, Embase, the Web of Science and CBM databases was conducted from their inception through to October 2012. Crude standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the effect of breathing exercises. A total of eight clinical studies were ultimately included with 398 lung cancer patients. When all the eligible studies were pooled into the meta-analysis, there was a significant difference between the pre-intervention and post-intervention results of breathing exercises on post-operative pulmonary function; forced expiratory volume in 1 sec (FEV1): SMD, 3.37; 95% CI, 1.97-4.77; Pintervention with breathing exercises; there were significant differences between the pre-intervention and post-intervention results on the ability of self-care in daily life (SMD, -1.00; 95% CI, -1.467 to -0.52; P<0.001), social activities (SMD, -0.94; 95% CI, -1.73 to -0.15; P=0.02), symptoms of depression (SMD, -0.91; 95% CI, -1.25 to -0.57; P<0.001) and symptoms of anxiety (SMD, -0.91; 95% CI, -1.20 to -0.63; P<0.001). Results from the present meta-analysis suggest that breathing exercises may significantly improve post-operative pulmonary function and QOL in patients with lung cancer.

  6. "Triple negative breast cancer": Translational research and the (re)assembling of diseases in post-genomic medicine.

    Science.gov (United States)

    Keating, Peter; Cambrosio, Alberto; Nelson, Nicole C

    2016-10-01

    The paper examines the debate about the nature and status of "Triple-negative breast cancer", a controversial biomedical entity whose existence illustrates a number of features of post-genomic translational research. The emergence of TNBC is intimately linked to the rise of molecular oncology, and, more generally, to the changing configuration of the life sciences at the turn of the new century. An unprecedented degree of integration of biological and clinical practices has led to the proliferation of bio-clinical entities emerging from translational research. These translations take place between platforms rather than between clinical and laboratory settings. The complexity and heterogeneity of TNBC, its epistemic and technical, biological and clinical dualities, result from its multiple instantiations via different platforms, and from the uneven distribution of biological materials, techniques, and objects across clinical research settings. The fact that TNBC comes in multiple forms, some of which seem to be incompatible or, at least, only partially overlapping, appears to be less a threat to the whole endeavor, than an aspect of an ongoing translational research project. Discussions of translational research that rest on a distinction between basic research and its applications fail to capture the dynamics of this new domain of activity, insofar as application is built-in from the very beginning in the bio-clinical entities that emerge from the translational research domain.

  7. [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.

  8. 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.

  9. Estrogen receptor β exerts tumor repressive functions in human malignant pleural mesothelioma via EGFR inactivation and affects response to gefitinib.

    Directory of Open Access Journals (Sweden)

    Giulia Pinton

    Full Text Available BACKGROUND: The role of estrogen and estrogen receptors in oncogenesis has been investigated in various malignancies. Recently our group identified estrogen receptor beta (ERβ expression as an independent prognostic factor in the progression of human Malignant Pleural Mesothelioma (MMe, but the underlying mechanism by which ERβ expression in tumors determines clinical outcome remains largely unknown. This study is aimed at investigating the molecular mechanisms of ERβ action in MMe cells and disclosing the potential translational implications of these results. METHODS: We modulated ERβ expression in REN and MSTO-211H MMe cell lines and evaluated cell proliferation and EGF receptor (EGFR activation. RESULTS: Our data indicate that ERβ knockdown in ER positive cells confers a more invasive phenotype, increases anchorage independent proliferation and elevates the constitutive activation of EGFR-coupled signal transduction pathways. Conversely, re-expression of ERβ in ER negative cells confers a more epithelioid phenotype, decreases their capacity for anchorage independent growth and down-modulates proliferative signal transduction pathways. We identify a physical interaction between ERβ, EGFR and caveolin 1 that results in an altered internalization and in a selective reduced activation of EGFR-coupled signaling, when ERβ is over-expressed. We also demonstrate that differential expression of ERβ influences MMe tumor cell responsiveness to the therapeutic agent: Gefitinib. CONCLUSIONS: This study describes a role for ERβ in the modulation of cell proliferation and EGFR activation and provides a rationale to facilitate the targeting of a subgroup of MMe patients who would benefit most from therapy with Gefitinib alone or in combination with Akt inhibitors.

  10. Spectroscopic and molecular docking studies of binding interaction of gefitinib, lapatinib and sunitinib with bovine serum albumin (BSA).

    Science.gov (United States)

    Shen, Guo-Feng; Liu, Ting-Ting; Wang, Qi; Jiang, Min; Shi, Jie-Hua

    2015-12-01

    The binding interactions of three kinds of tyrosine kinase inhibitors (TKIs), such as gefitinib, lapatinib and sunitinib, with bovine serum albumin (BSA) were studied using ultraviolet spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR) and molecular docking methods. The experimental results showed that the intrinsic fluorescence quenching of BSA induced by the three TKIs resulted from the formation of stable TKIs-BSA complexes through the binding interaction of TKIs with BSA. The stoichiometry of three stable TKIs-BSA complexes was 1:1 and the binding constants (Kb) of the three TKIs-BSA complexes were in the order of 10(4)M(-1) at 310 K, indicating that there was a strong binding interaction of the three TKIs with BSA. Based on the analysis of the signs and magnitudes of the free energy change (ΔG(0)), enthalpic change (ΔH(0)) and entropic change (ΔS(0)) in the binding process, it can be deduced that the binding process of the three TKIs with BSA was spontaneous and enthalpy-driven process, and the main interaction forces between the three TKIs and BSA were van der Waals force and hydrogen bonding interaction. Moreover, from the results of CD, FT-IR and molecular docking, it can be concluded that there was a significant difference between the three TKIs in the binding site on BSA, lapatinib was located on site II (m) of BSA while gefitinib and sunitinib were bound on site I of BSA, and there were some changes in the BSA conformation when binding three TKIs to BSA but BSA still retains its secondary structure α-helicity.

  11. The promotion of salinomycin on the apoptosis of human lung adenocarcinoma cell line PC9 induced by gefitinib%盐霉素增强吉非替尼诱导人肺腺癌细胞株PC9凋亡作用

    Institute of Scientific and Technical Information of China (English)

    曾葭; 祝爱珍; 刘成成; 陈小宇; 谭广销; 刘革修

    2012-01-01

    目的:探讨盐霉素联合吉非替尼诱导人肺腺癌细胞株PC9凋亡作用.方法:MTT法检测细胞增殖活性;流式细胞仪检测细胞凋亡及线粒体膜电位(MMP);比色法检测Caspase-3、8和9酶活性;Western blot分析细胞色素C、bcl-2、p-EGFR、p-Akt和p-ERK蛋白水平.结果:盐霉素与吉非替尼单用均出现不同程度的细胞增殖抑制作用和诱导细胞凋亡作用;而两者合用则能更显著地抑制细胞增殖,且细胞凋亡显著增加(P<0.05).盐霉素单独作用,细胞MMP显著下降,细胞内活性氧和Ca2+在短期显著升高,胞浆细胞色素C、Caspase-3、8和9酶活性均显著增加;吉非替尼单用则抑制p-EGFR、p-Akt和p-ERK蛋白表达,而对胞浆细胞色素C、Caspase-3、8和9酶活性影响较少.Western印迹检测发现,联合用药组的Bcl-2、p-EGFR、p-Akt和p-ERK蛋白表达量明显减少.结论:盐霉素与吉非替尼联用具有较好的协同作用,提高PC9细胞对吉非替尼的敏感性.%Objective To investigate the effects of salinomycin combined with gefitinib on the apoptosis of human non-small cell lung cancer cell line PC9. Methods The growth of PC9 cells was tested by MTT, cell apoptosis and mitochondria membrane potential (MMP) were measured by flow cytometry, the activities of caspase-3,8, and 9 were detected by colorimetry, and the levels of cytochrome C, bcl-2, p-EGFR, p-Akt, and p-ERK were analyzed by Western blot. Results Salinomycin or gefitinib alone could inhibit the growth and induce the apoptosis of PC9 cells in a dose-dependent manner; when they were combined with each other, these effects were more obvious (P < 0.05). Salinomycin alone could significantly reduce the MMP and increase the levels of intracellular reactive oxygen species (ROS), cytoplasmic cytochrome C, and cytosolic Ca2+, and the activities of caspase-3, 8, and 9. Gefitinib alone could inhibit the expressions of p-EGFR, p-Akt, and p-ERK protein, and less affect the level of

  12. 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...... 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...

  13. The inhibitory effects of the combination of pemetrexed and BIBW2992 or gefitinib respectively on human lung adenocarcinoma cell line%阿法替尼和吉非替尼分别联合培美曲塞对人肺腺癌细胞作用的研究

    Institute of Scientific and Technical Information of China (English)

    边劲; 王琳; 寻琛; 黄伟

    2014-01-01

    Objective To investigate the potential anti-proliferative and pro-apoptotic effects of the combination of pemetrexed and afatinib(BIBW2992) or gefitinib respectively on gefitinib-sensitive cells (PC-9) and gefitinib-re-sistant cells with the T790M mutation of EGFR(H1975) and explore its possible anti-cancer mechanism. Methods MTT assay was performed to reveal the inhibitory effect on cell proliferation. Flow cytometry using annexin V-FITC/PI staining was employed to measure the cell apoptosis and cell cycle. Western blot was performed to detect the protein expressions of thymidylate synthase ( TS) after treated with different dose of BIBW2992 and gefitinib re-spectively . Results The PC-9 and H1975 cells were inhibited to different degrees after treatment with BIBW2992 , gefitinib and pemetrexed alone and had apparent apoptotic features. The combined treatment with BIBW2992 and pemetrexed resulted in a synergistic effect in inducing apoptosis and inhibiting cell proliferation compared with BIBW2992 and pemetrexed alone both on the PC-9 and H1975 cells(P<0. 05). The combined treatment with ge-fitinib and pemetrexed resulted in a synergistic effect only on the PC-9 cells(P<0. 05), whereas had no such syn-ergistic effect on the H1975 cells. The BIBW2992 decreased the expressions of TS apparently both on the PC-9 cells and H1975 cells, whereas gefitinib had no such effect on the H1975 cells. Conclusion The BIBW2992 can overcome the drug resistance of cells with the T790M mutation of EGFR. The combination of BIBW2992 and peme-trexed has an enhanced antitumor effect on both PC-9 cells and H1975 cells, whereas the combination of gefitinib and pemetrexed has an enhanced antitumor effect only on PC-9 cells, with the possible mechanism of ability to sup-press the expression of TS.%目的:探讨阿法替尼(BIBW2992)和吉非替尼分别与培美曲塞联合对肺腺癌细胞 PC-9(突变敏感型)、H1975(T790M耐药型)的增殖和凋亡的影响并

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

    Science.gov (United States)

    Sartor, A Oliver

    2011-04-23

    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-mediated signaling on m

  15. 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

  16. Combined inhibition of epidermal growth factor receptor and cyclooxygenase-2 leads to greater anti-tumor activity of docetaxel in advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jianzhong Lin

    Full Text Available The epidermal growth factor receptor (EGFR and cyclooxygenase-2(COX-2 play a critical role in disease progression, relapse and therapeutic resistance of advanced prostate cancer (PCa. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking EGRF and/or COX-2 (using gefitinib and NS-398, respectively in terms of improving the efficacy of the conventional clinical chemotherapeutic drug docetaxel in vitro and vivo. We showed that EGFR and COX-2 expression was higher in metastatic than non-metastatic PCa tissues and cells. Docetaxel, alone or in combination with gefitinib or NS-398, resulted in a small decrease in cell viability. The three drug combination decreased cell viability to a greater extent than docetaxel alone or in combination with gefitinib or NS-398. Docetaxel resulted in a modest increase in apoptotic cell in metastatic and non-metastatic cell lines. NS-398 markedly enhanced docetaxel-induced cell apoptosis. The combination of the three drugs caused even more marked apoptosis and resulted in greater suppression of invasive potential than docetaxel alone or in association with gefitinib or NS-398. The combination of all three drugs also resulted in a more marked decrease in NF-ΚB, MMP-9 and VEGF levels in PC-3M cells. These in vitro findings were supported by in vivo studies showing that docetaxel in combination with gefitinib and NS-398 was significantly more effective than any individual agent. Based on previous preclinical research, we conclude that simultaneously blocking EGFR and COX-2 by gefitinib and NS-398 sensitizes advanced PCa cells to docetaxel-induced cytotoxicity.

  17. p14ARF post-transcriptional regulation of nuclear cyclin D1 in MCF-7 breast cancer cells: discrimination between a good and bad prognosis?

    Directory of Open Access Journals (Sweden)

    Eileen M McGowan

    Full Text Available As part of a cell's inherent protection against carcinogenesis, p14ARF is upregulated in response to hyperproliferative signalling to induce cell cycle arrest. This property makes p14ARF a leading candidate for cancer therapy. This study explores the consequences of reactivating p14ARF in breast cancer and the potential of targeting p14ARF in breast cancer treatment. Our results show that activation of the p14ARF-p53-p21-Rb pathway in the estrogen sensitive MCF-7 breast cancer cells induces many hallmarks of senescence including a large flat cell morphology, multinucleation, senescence-associated-β-gal staining, and rapid G1 and G2/M phase cell cycle arrest. P14ARF also induces the expression of the proto-oncogene cyclin D1, which is most often associated with a transition from G1-S phase and is highly expressed in breast cancers with poor clinical prognosis. In this study, siRNA knockdown of cyclin D1, p21 and p53 show p21 plays a pivotal role in the maintenance of high cyclin D1 expression, cell cycle and growth arrest post-p14ARF induction. High p53 and p14ARF expression and low p21/cyclin D1 did not cause cell-cycle arrest. Knockdown of cyclin D1 stops proliferation but does not reverse senescence-associated cell growth. Furthermore, cyclin D1 accumulation in the nucleus post-p14ARF activation correlated with a rapid loss of nucleolar Ki-67 protein and inhibition of DNA synthesis. Latent effects of the p14ARF-induced cellular processes resulting from high nuclear cyclin D1 accumulation included a redistribution of Ki-67 into the nucleoli, aberrant nuclear growth (multinucleation, and cell proliferation. Lastly, downregulation of cyclin D1 through inhibition of ER abrogated latent recurrence. The mediation of these latent effects by continuous expression of p14ARF further suggests a novel mechanism whereby dysregulation of cyclin D1 could have a double-edged effect. Our results suggest that p14ARF induced-senescence is related to late

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

    Directory of Open Access Journals (Sweden)

    Arathi

    2015-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  20. 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

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

    OpenAIRE

    Mwaka, A. D.; Orach, C.G.; Were, E.M.; Lyratzopoulos, G; Wabinga, H.; Roland, M.

    2016-01-01

    Abstract Background Lack of awareness of risk factors and symptoms for cancer may lead to late diagnosis and poor prognosis. Objective 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. Design Cross‐sectional population‐based survey. Setting and participants We conducted this study in Gulu, a post‐conflict district i...

  2. Oesophagectomy rates and post-resection outcomes in patients with cancer of the oesophagus and gastro-oesophageal junction: a population-based study using linked health administrative linked data

    Directory of Open Access Journals (Sweden)

    Stavrou Efty P

    2012-11-01

    Full Text Available Abstract Background Hospital performance is being benchmarked increasingly against surgical indicators such as 30-day mortality, length-of-stay, survival and post-surgery complication rates. The aim of this paper was to examine oesophagectomy rates and post-surgical outcomes in cancers of the oesophagus and gastro-oesophageal junction and to determine how the addition of gastro-oesophageal cancer to oesophageal cancer impacts on these outcomes. Methods Our study population consisted of patients with a primary invasive oesophageal or gastro-oesophageal cancer identified from the NSW Cancer Registry from July 2000-Dec 2007. Their records were linked to the hospital separation data for determination of resection rates and post-resection outcomes. We used multivariate logistic regression analyses to examine factors associated with oesophagectomy and post-resection outcomes. Cox-proportional hazard regression analysis was used to examine one-year cancer survival following oesophagectomy. Results We observed some changes in resection rates and surgical outcomes with the addition of gastro-oesophageal cancer patients to the oesophageal cancer cohort. 14.6% of oesophageal cancer patients and 26.4% of gastro-oesophageal cancer patients had an oesophagectomy; an overall oesophagectomy rate of 18.2% in the combined cohort. In the combined cohort, oesophagectomy was associated with younger age, being male and Australian-born, having non-metastatic disease or adenocarcinoma and being admitted in a co-located hospital. Rates of length-of-stay >28 days (20.9% vs 19.7%, 30-day mortality (3.8% vs 2.7% and one-year survival post-surgery (24.5% vs 23.1% were similar between oesophageal cancer alone and the combined cohort; whilst 30-day complication rates were 21.5% versus 17.0% respectively. Some factors statistically associated with post-resection complication in oesophageal cancer alone were not significant in the overall cohort. Poorer post-resection outcomes

  3. Circulating oxidative stress parameters in pre- and post-menopausal healthy women and in women suffering from breast cancer treated or not with neoadjuvant chemotherapy.

    Science.gov (United States)

    Ramírez-Expósito, María Jesús; Sánchez-López, Estefanía; Cueto-Ureña, Cristina; Dueñas, Basilio; Carrera-González, Pilar; Navarro-Cecilia, Joaquín; Mayas, María Dolores; Arias de Saavedra, José M; Sánchez-Agesta, Rafael; Martínez-Martos, José M

    2014-10-01

    We evaluate here the redox status in pre- and post-menopausal healthy women and in women with breast cancer in order to understand the consequences of the hormonal alterations of menopause for the oxidative stress status, its modifications with breast cancer and the influence of neoadjuvant chemotherapy (NC). To that, serum oxidative stress parameters (total antioxidant capacity, lipid peroxidation and protein oxidation), non-enzyme antioxidant defenses (total glutathione, uric acid and bilirubin) and enzyme antioxidant defenses (superoxide dismutase, catalase and glutathione peroxidase activities) were measured in healthy women and in women with breast cancer divided according to their menopausal status and that received or not NC. Circulating estradiol, progesterone, FSH and LH were also analyzed. We found that menopause itself modifies the redox status of healthy women, being most of these differences also reflected in women with breast cancer. However, several changes occur as a consequence of the disease. Furthermore, NC increases oxidative damage, decreases antioxidant defenses and eliminates the differences found in menopause. We conclude that the normal redox balance is disrupted by breast cancer but is also affected by the hormonal status promoted by menopause. In fact, NC nullifies the differences found between pre- and postmenopausal women in several antioxidant defense systems.

  4. 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.

  5. Peri and post-menopausal women with complex adnexal masses, ascites, and raised CA-125: Is it ovarian cancer or tuberculosis?

    Science.gov (United States)

    Bagga, Rashmi; Muthyala, Tanuja; Saha, Subhas Chandra; Gainder, Shalini; Saha, Pradip Kumar; Srinivasan, Radhika; Rajwanshi, Arvind; Gupta, Nalini

    2016-01-01

    Pelvic and peritoneal tuberculosis may resemble advanced ovarian cancer due to the presence of ascites, complex adnexal masses, peritoneal deposits and raised CA-125 level, especially in peri- and postmenopausal women. Other common features among women with these two conditions are abdominal pain and distension, weight loss and reduced appetite. As the treatment of pelvic-peritoneal tuberculosis is completely different from that of ovarian cancer, it is important to reach a correct diagnosis. Sometimes women with pelvic-peritoneal tuberculosis may be subjected to a laparotomy for suspected ovarian cancer which is likely to increase their morbidity. In the present article, we report ten women in the peri- and post-menopausal age group where this diagnostic dilemma arose of whom seven were diagnosed only after a laparotomy had been performed for suspected ovarian cancer due to adnexal masses with ascites and raised CA-125 level. Ascitic fluid showing lymphocytic predominance, raised ADA level and absence of malignant cells are pointers to consider the possibility of pelvic- peritoneal tuberculosis, especially in endemic countries like India. In such situations, an effort should be made to obtain a cytological or histopathological diagnosis of either condition by ultrasound guided needle biopsy or laparoscopically obtained biopsy rather that proceeding with laparotomy for suspected ovarian cancer. PMID:28096645

  6. Post-transcriptional regulation of cyclins D1, D3 and G1 and proliferation of human cancer cells depend on IMP-3 nuclear localization.

    Science.gov (United States)

    Rivera Vargas, T; Boudoukha, S; Simon, A; Souidi, M; Cuvellier, S; Pinna, G; Polesskaya, A

    2014-05-29

    RNA-binding proteins of the IMP family (insulin-like growth factor 2 (IGF2) mRNA-binding proteins 1-3) are important post-transcriptional regulators of gene expression. Multiple studies have linked high expression of IMP proteins, and especially of IMP-3, to an unfavorable prognosis in numerous types of cancer. The specific importance of IMP-3 for cancer transformation remains poorly understood. We here show that all three IMPs can directly bind the mRNAs of cyclins D1, D3 and G1 (CCND1, D3 and G1) in vivo and in vitro, and yet only IMP-3 regulates the expression of these cyclins in a significant manner in six human cancer cell lines of different origins. In the absence of IMP-3, the levels of CCND1, D3 and G1 proteins fall dramatically, and the cells accumulate in the G1 phase of the cell cycle, leading to almost complete proliferation arrest. Our results show that, compared with IMP-1 and IMP-2, IMP-3 is enriched in the nucleus, where it binds the transcripts of CCND1, D3 and G1. The nuclear localization of IMP-3 depends on its protein partner HNRNPM and is indispensable for the post-transcriptional regulation of expression of the cyclins. Cytoplasmic retention of IMP-3 and HNRNPM in human cancer cells leads to significant drop in proliferation. In conclusion, a nuclear IMP-3-HNRNPM complex is important for the efficient synthesis of CCND1, D3 and G1 and for the proliferation of human cancer cells.

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

    DEFF Research Database (Denmark)

    Hartmann, Stefan; Brands, Roman C; Küchler, Nora;

    2015-01-01

    receptor (EGFR). The efficacy of tyrosine kinase inhibitors (TKI) in the context of melanoma-associated antigens is discussed in the present study. Five human squamous cell carcinoma cell lines were treated with the EGFR TKIs, erlotinib and gefitinib. The efficacy of these agents was measured using......Melanoma-associated antigen (MAGE) has been identified in a variety of types of cancer. The expression of several MAGE subgroups is correlated with poor prognosis and chemotherapeutic resistance. One target of chemotherapeutic treatment in head and neck cancer is the epidermal growth factor...... correlation between MAGE-A5 and -A11 and lower efficacy of EGFR TKIs. Pretreatment analysis of MAGE-A status may therefore aid improvement of chemoprevention using erlotinib and gefitinib in head and neck cancer....

  8. Targeting the EGFR pathway for cancer therapy

    DEFF Research Database (Denmark)

    Johnston, JB; Navaratnam, S; Pitz, MW

    2006-01-01

    provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side......Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally...... effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e...

  9. African Americans and Prostate Cancer: A Spatial and Multilevel Analysis of Post-treatment Care and Outcomes

    Science.gov (United States)

    2008-08-01

    5 2.2.2. Geocoded prostate cancer data set development 5 2.3. Task 2: Integrate data to build GIS and conduct exploratory spatial...of the SEER-Medicare data set, the development and construction of the prostate cancer geocoded data set, and the GIS database development. Under...From this data file, 2 geocoded prostate cancer data sets were developed: one with all cases in the SEER-Medicare data set, and a second that

  10. [Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

    Science.gov (United States)

    Shimada, Yasuhiro

    2016-04-01

    The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shih-Chieh Chang

    2011-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Adriaenssens Nele

    2012-05-01

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

  15. 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

    Background: Pelvic magnetic resonance imaging in patients with rectal cancer is an accepted tool for the identification of patients with poor prognostic tumours who may benefit from neo-adjuvant therapy. In Denmark, the examination has been mandatory in the work-up on rectal cancer since 2002....... Objective: To assess the impact of a multidisciplinary team course for doctors in West Denmark on the technical quality, reporting and interpretation of pelvic MRI in rectal cancer. Design: Interventional, observational study. Two expert reviewers served as reference standard in the evaluation...... cancer were enrolled. Interventions: A multidisciplinary team course including on-site-visits. Main Outcome Measures: The MR-scans were evaluated concerning technical performance, reporting, interpretation and the ability to correctly allocate patients to chemo-irradiation based on imaging findings pre...

  16. Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Wang, Yi-Ting; Pan, Szu-Hua; Tsai, Chia-Feng; Kuo, Ting-Chun; Hsu, Yuan-Ling; Yen, Hsin-Yung; Choong, Wai-Kok; Wu, Hsin-Yi; Liao, Yen-Chen; Hong, Tse-Ming; Sung, Ting-Yi; Yang, Pan-Chyr; Chen, Yu-Ju

    2017-01-01

    Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins. CK2 knockdown decreased cell survival in gefitinib-resistant NSCLCs. Using motif analysis to identify the CK2 core sub-network, we verified that elevated phosphorylation level of a CK2 substrate, HMGA1 was a critical node contributing to EGFR-TKI resistance in NSCLC cell. Both HMGA1 knockdown or mutation of the CK2 phosphorylation site, S102, of HMGA1 reinforced the efficacy of gefitinib in resistant NSCLC cells through reactivation of the downstream signaling of EGFR. Our results delineate the TKI resistance-associated kinase-substrate network, suggesting a potential therapeutic strategy for overcoming TKI-induced resistance in NSCLC. PMID:28290473

  17. 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...

  18. A phase I and pharmacokinetics study of intravenous calcitriol in combination with oral dexamethasone and gefitinib in patients with advanced solid tumors

    Science.gov (United States)

    Muindi, Josephia R.; Johnson, Candace S.; Trump, Donald L.; Christy, Renee; Engler, Kristie L.

    2009-01-01

    Purpose The primary objective of this study was to determine the maximum tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in combination with a fixed oral dose of dexamethasone and gefitinib in patients with refractory solid tumors. Methods A fixed oral dose of dexamethasone of 4 mg/day was given every 12 h × 3 doses starting 12 h prior to i.v. calcitriol administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and weekly thereafter. The starting calcitriol dose level was 57 μg and escalation occurred in cohorts of three patients until the MTD was defined. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Serum calcitriol PK studies were performed on day 1 (calcitriol + dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). Results A total of 20 patients were treated. Dose-limiting hypercalcemia was observed in two out of the four patients receiving 163 mcg/week of calcitriol. Mean (±SE) peak serum calcitriol concentration (Cmax) at the MTD (125 μg/week calcitriol) was 11.17 ± 2.62 ng/ml and the systemic exposure (AUC0–72 h) of 53.30 ± 10.49 ng h/ml. The relationship between calcitriol dose and either Cmax or AUC was linear over the 57–163 μg dose range. Conclusions The addition of a low dose of dexamethasone allowed the safe escalation of calcitriol to the MTD of 125 μg/week. This dose level resulted in serum calcitriol concentrations that are associated with pre-clinical antitumor activity. However, no antitumor activity was noted clinically in patients with solid tumors. PMID:19396601

  19. LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Yun-Ting Lou

    Full Text Available Methylation levels of long interspersed nucleotide elements (LINE-1 are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients.129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes.The LINE-1 methylation of all 129 patients was measured on a 0-100 scale (mean 63.3; median 63.7, standard deviation 7.1, LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019 and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041. Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012. Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01. In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7.57, p=0.041.There was a

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Vislovukh A. A.

    2013-01-01

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

  2. 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.

  3. Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer

    DEFF Research Database (Denmark)

    Gilbert, Duncan C; Serup-Hansen, Eva; Linnemann, Dorte

    2016-01-01

    BACKGROUND: The majority (90%) of anal cancers are human papillomavirus (HPV)-driven, identified using immunochemistry for p16. Compared with HPV- patients, those with HPV+ disease generally show improved survival, although relapse rates around 25% indicate a need for further stratification...... of this group. METHODS: Using two cohorts of anal cancer, previously characterised for p16, we assessed the prognostic value of tumour-infiltrating lymphocytes (TILs). RESULTS: Tumour-infiltrating lymphocyte scores were used to stratify p16+ cases, where tumours with absent/low levels of TIL had a relapse......-free rate of 63%, as opposed to 92% with high levels of TIL (log rank P=0.006). CONCLUSIONS: Assessment of TIL adds to p16 status in the prognosis of anal cancer following chemo-radiotherapy and provides evidence of the clinical importance of the immune response....

  4. 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...

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  6. Body composition alterarions, energy expenditure and fat oxidation in elderly males suffering from prostate cancer, pre and post orchiectomy

    Directory of Open Access Journals (Sweden)

    Cristiana Reis

    2009-01-01

    Full Text Available INTRODUCTION: Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects. OBJECTIVE: This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer. PATIENTS AND METHODS: A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63-96; median age 71 with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry. RESULTS: Body weight (p=0.01, lean mass (p=0.004, and lipid oxidation (p=0.001 decreased significantly. Carbohydrate oxidation (p=0.02, FSH (p=0.0001 and LH (p=0.0001 levels increased significantly. Changes in fat mass (p=0.06 and bone mineral density (p=0.48 were not significant. CONCLUSIONS: After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.

  7. 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

    2017-03-03

    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 < 0.0001), mean pH values (p = 0.0002 and p = 0.0004), and mean score from the quality of life questionnaire (p < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

  8. Role of receptor tyrosine kinases in gastric cancer: New targets for a selective therapy

    Institute of Scientific and Technical Information of China (English)

    JC Becker; C Müller-Tidow; H Serve; W Domschke; T Pohle

    2006-01-01

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab,cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.

  9. The impact of thyroid cancer and post-surgical radioactive iodine treatment on the lives of thyroid cancer survivors: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Anna M Sawka

    Full Text Available BACKGROUND: Adjuvant treatment with radioactive iodine (RAI is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC. We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment. METHODS: We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups. FINDINGS: There were 16 participants in the study, twelve of whom were women (75%. All but one participant had received RAI treatment (94%. Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers. CONCLUSIONS: The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors.

  10. Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

    Science.gov (United States)

    Boyer, Matthew J; Gu, Lin; Wang, Xiaofei; Kelsey, Chris R; Yoo, David S; Onaitis, Mark W; Dunphy, Frank R; Crawford, Jeffrey; Ready, Neal E; Salama, Joseph K

    2016-08-01

    To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

  11. Post-surgical highly sensitive C-reactive protein and prognosis in early-stage breast cancer.

    Science.gov (United States)

    Tibau, Ariadna; Ennis, Marguerite; Goodwin, Pamela J

    2013-10-01

    Obesity, associated with inflammation, has been linked to poor prognosis in breast cancer. Research investigating the potential role of C-reactive protein (CRP), an obesity-associated systemic marker of inflammation, as a mediator of adverse prognostic effects of obesity has yielded inconsistent results. We examined the association of highly sensitive CRP (hsCRP) with obesity-related factors and breast cancer outcome. A cohort of 535 non-diabetic women diagnosed with T1-3, N0-1, M0 breast cancer, was assembled between 1989 and 1996 and followed prospectively. Circulating levels of hsCRP were analyzed on blood obtained postoperatively, prior to systemic therapy, in 501 women. Correlations and prognostic associations were analyzed using one-way analysis of variance, Spearman's rank correlation coefficients (r) and Cox models. hsCRP was significantly correlated with body mass index (r = 0.60), insulin (r = 0.44), leptin (r = 0.54), and lipids, but not T or N stage, grade or estrogen receptor/progesterone receptor. At a median follow-up of 12 years, hsCRP was not associated with distant disease-free survival or overall survival in univariable [Q4 vs. Q1 hazard ratio (HR) 1.03, 95 % confidence interval (CI) 0.69-1.52, P = 0.9 and HR 1.27, 95 % CI 0.86-1.86, P = 0.24, respectively] or multivariable [Q4 vs Q1 HR 1.02, 95 % CI 0.66-1.59, P = 0.93 and HR 1.17, 95 % CI 0.76-1.81, P = 0.48 respectively] analyses. hsCRP was associated with age, comorbidities, and the insulin resistance syndrome but not with breast cancer outcome.

  12. SU-E-T-14: A Feasibility Study of Using Modified AP Proton Beam for Post-Operative Pancreatic Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ding, X; Witztum, A; Kenton, O; Younan, F; Dormer, J; Kremmel, E; Lin, H; Liu, H; Tang, S; Both, S; Kassaee, A; Avery, S [UniversityPennsylvania, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Due to the unpredictability of bowel gas movement, the PA beam direction is always favored for robust proton therapy in post-operative pancreatic cancer treatment. We investigate the feasibility of replacing PA beam with a modified AP beam to take the bowel gas uncertainty into account. Methods: Nine post-operative pancreatic cancer patients treated with proton therapy (5040cGy, 28 fractions) in our institution were randomly selected. The original plan uses PA and lateral direction passive-scattering proton beams. Beam weighting is about 1:1. All patients received weekly verification CTs to assess the daily variations(total 17 verification CTs). The PA direction beam was replaced by two other groups of AP direction beam. Group AP: takes 3.5% range uncertainty into account. Group APmod: compensates the bowel gas uncertainty by expanding the proximal margin to 2cm more. The 2cm margin was acquired from the average bowel diameter in from 100 adult abdominal CT scans near pancreatic region (+/- 5cm superiorly and inferiorly). Dose Volume Histograms(DVHs) of the verification CTs were acquired for robustness study. Results: Without the lateral beam, Group APmod is as robust as Group PA. In Group AP, more than 10% of iCTV D98/D95 were reduced by 4–8%. LT kidney and Liver dose robustness are not affected by the AP/PA beam direction. There is 10% of chance that RT kidney and cord will be hit by AP proton beam due to the bowel gas. Compared to Group PA, APmod plan reduced the dose to kidneys and cord max significantly, while there is no statistical significant increase in bowel mean dose. Conclusion: APmod proton beam for the target coverage could be as robust as the PA direction without sacrificing too much of bowel dose. When the AP direction beam has to be selected, a 2cm proximal margin should be considered.

  13. 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

  14. [Clinical and morphological features of papillary thyroid cancer in children and adolescents in the Republic of Belarus: analysis of 936 post-Chernobyl carcinomas].

    Science.gov (United States)

    Fridman, M V; Man'kovskaia, S V; Kras'ko, O V; Demidchik, Iu E

    2014-01-01

    There is presented clinical and morphological characteristics of post-Chernobyl papillary thyroid cancer in 936 children and adolescents. In general, carcinoma of these patients featured by locally advanced growth - 57.4% (387 of 674 patients with this sign could be assessed), metastases in regional lymph nodes - 73,7% (N1b in 40.7%) and internal organs - 11.1%. The mean duration of follow-up was 12,4 +/- 3,5 years (range 4.3 to 19.6 years) including children 14,6 +/- 2,7 years (range 8.8 to 19.6 years) and adolescents - 10,1 +/- 3,1 years (range 4.3 to 18.8 years). Overall survival for the 20-year period was 96,6% +/- 1,2%. The causes of death were suicide (7), injuries and accidents (5), secondary malignancies (1), somatic diseases (2). Only in two patients the death was related to the main disease - lung metastases. Free-recurrence survival for the cohort of post-Chernobyl carcinomas was 92,7% +/- 1,0%.

  15. 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)

  16. [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.

  17. SU-E-P-56: Dosimetric Comparison of Three Post Modified Radical Mastectomy Radiotherapy Techniques for Locally Advanced Left-Sided Breast Cancer and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Zhang, W; Lu, J; Wu, L; Wu, F; Huang, B; Li, D [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China)

    2015-06-15

    Purpose: To compare the dosimetry of post modified radical mastectomy radiotherapy (PMRMRT) for left-sided breast cancer using 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: We created ten sets of PMRMRT plans for ten consecutive patients and utilized two tangential and one or two supraclavicular beams in 3DCRT, a total of 5 beams in IMRT and two optimized partial arcs in VMAT. The difference in results between any two of the three new plans, between new and previous 3DCRT plans were compared and analyzed by ANOVA (α =0.05) and paired-sample t-test respectively. P values less than 0.05 were considered statistically significant. Results: Both IMRT and VMAT plans had similar PTV coverage, hotspot area and conformity (all p>0.05), and significantly higher PTV coverage compared with new 3DCRT (both p<0.001). IMRT plans had significantly less heart and left lung radiation exposure compared with VMAT (all p<0.05). The 3DCRT plans with larger estimated CTV displacement had better target coverage but worse OARs sparing compared to those with smaller one. Conclusion: IMRT has dosimetrical advantages over the other two techniques in PMRMRT for left-sided breast cancer. Individually quantifying and minimizing CTV displacement can significantly improve dosage distribution. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)

  18. [Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

    Science.gov (United States)

    Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

    2014-04-01

    The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

  19. Metabolic Response on Post-therapy FDG-PET Predicts Patterns of Failure After Radiotherapy for Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Siegel, Barry A.; Dehdashti, Farrokh [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Grigsby, Perry W. [Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States)

    2012-05-01

    Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and Materials: The records of 238 patients with cervical cancer were reviewed. All patients were treated with a combination of external radiotherapy and intracavitary brachytherapy. Two hundred and nineteen patients (92%) received concurrent chemotherapy. All patients underwent pretreatment FDG-PET, and posttherapy FDG-PET was performed within 8-16 weeks of the completion of radiotherapy. Posttherapy FDG-PET results were categorized as complete metabolic response (CMR), partial metabolic response (PMR), and progressive disease (PD). Failure patterns were categorized as none, isolated local failure (central pelvis {+-} pelvic lymph nodes), distant failure, or combined local plus distant failure. Results: Of the 91 patients (38%) who had a recurrence, 22 had isolated local failures, and 69 had distant failures (49 distant failures and 20 combined local plus distant failures). Of the 173 patients with a CMR, 40 (23%) experienced treatment failure. All 25 patients with PD experienced treatment failure, which was distant in 24 patients (96%). Among the 40 patients with PMR, no failure has been observed for 14 patients (35%). Of the 26 failures within the PMR group, 15 (58%) were limited to the pelvis. Differences in the patterns of failure between the three groups (CMR, PMR, PD) were statistically significant (chi-square test; p < 0.0001). Conclusions: The majority of failures after definitive radiotherapy for cervical cancer include distant failures, even in the setting of concurrent chemotherapy. PMR within the cervix or lymph nodes is more commonly associated with isolated local recurrence.

  20. Clinical role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in post-operative follow up of gastric cancer: Initial results

    Institute of Scientific and Technical Information of China (English)

    Long Sun; Xin-Hui Su; Yong-Song Guan; Wei-Ming Pan; Zuo-Ming Luo; Ji-Hong Wei; Hua Wu

    2008-01-01

    AIM: To evaluate the clinical role of 18F-fluorodeo-xyglucose positron emission and computed tomography(18F-FDG PET/CT) in detection of gastric cancer recur rence after initial surgical resection.METHODS: In the period from January 2007 to May 2008, 23 patients who had previous surgical resection of histopathologically diagnosed gastric cancer underwent a total of 25 18F-FDG PET/CT scans as follow-up visits in our center. The standard of reference for tumor recurrence consisted of histopathologic confirmation or clinical follow-up information for at least 5 mo after PET/CT examinations.RESULTS: PET/Cr was positive in 14 patients (61%)and negative in 9 (39%). When correlated with final diagnosis, which was confirmed by histopathologic evidence of tumor recurrence in 8 of the 23 patients(35%) and by clinical follow-up in 15 (65%), PET/CT was true positive in 12 patients, false positive in 2,true negative in 8 and false negative in 2. Overall,the accuracy of PET/CT was 82.6%, the negative predictive value (NPV) was 77.7%, and the positive predictive value (PPV) was 85.7%. The 2 false positive PET/CT findings were actually chronic inflammatory tissue lesions. For the two patients with false negative PET/CT, the final diagnosis was recurrence of mucinous adenocarcinoma in the anastomosis in one patient and abdominal wall metastasis in the other. Importantly,PET/CT revealed true-positive findings in 11 (47.8%)patients who had negative or no definite findings by CT. PET/CT revealed extra-abdominal metastases in 7 patients and additional esophageal carcinoma in onepatient. Clinical treatment decisions were changed in 7 (30.4%) patients after introducing PET/CT into theirconventional post-operative follow-up program.CONCLUSION: Whole body 18F-FDG PET/CT was highly effective in discriminating true recurrence in post-operative patients with gastric cancer and had important impacts on clinical decisions in a considerable portion of patients.

  1. The TrkB+ cancer stem cells contribute to post-chemotherapy recurrence of triple-negative breast cancers in an orthotopic mouse model.

    Science.gov (United States)

    Yin, B; Ma, Z Y; Zhou, Z W; Gao, W C; Du, Z G; Zhao, Z H; Li, Q Q

    2015-02-01

    Cancer stem cells (CSCs) are believed to have a crucial role in triple-negative breast cancer (TNBC) recurrence. However, the exact mechanisms that are functionally critical in CSCs-mediated recurrence remain unclear. Here, we showed that CSCs derived from recurrent TNBCs are endowed with increased self-renewal capacity as compared with those from the matched primary lesions. Using patient-derived specimens, we demonstrated the existence of paracrine brain-derived neurotrophic factor (BDNF) signaling between differentiated recurrent TNBC cells and CSCs characterized by the expression of TrkB, the receptor of BDNF. We showed that paclitaxel induced BDNF expression and apoptosis simultaneously in a cell cycle-dependent manner. BDNF promotes the self-renewal potential of the TrkB+CSCs through induction of KLF4. The TrkB+CSCs represent a particular subset indispensable for TNBC relapse. In line with this, TrkB is proved to be a superior predictor for TNBC recurrence. Using a genetically engineered mouse model of TNBC, we observed that ablation of the TrkB+CSCs potentially prevents relapse of malignant tumors. Further preclinical investigation of this promising approach may lead to development of a novel therapeutic strategy to improve the devastating prognosis of TNBC patients.

  2. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Johnson; Baumgartner, Adolf; Lu, Chun-Mei; Wang, Mei; Weier, Jingly F.; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich G.

    2009-03-09

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  3. BAC-FISH assays delineate complex chromosomal rearrangements in a case of post-Chernobyl childhood thyroid cancer.

    Directory of Open Access Journals (Sweden)

    Horst F Zitzelsberger

    2009-12-01

    Full Text Available Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC, for example, activation of the receptor tyrosine kinase (RTK genes, RET and neurotrophic tyrosine kinase receptor type I (NTRK1 by intra- and interchromosomal rearrangements has been suggested as a cause of the disease. However, many phenotypically similar tumors do not carry an activated RET or NTRK-1 gene or express abnormal ret or NTRK-1 transcripts. Thus, we hypothesize that other cellular RTK-type genes are aberrantly expressed in these tumors. Using fluorescence in situ hybridization-based methods, we are studying karyotype changes in a relatively rare subgroup of PTCs, i.e., tumors that arose in children following the 1986 nuclear accident in Chernobyl, Ukraine. Here, we report our technical developments and progress in deciphering complex chromosome aberrations in case S48TK, an aggressively growing PTC cell line, which shows an unusual high number of unbalanced translocations.

  4. NMR Analysis of Targeted Drug Gefitinib%靶向新药吉非替尼的核磁共振波谱研究

    Institute of Scientific and Technical Information of China (English)

    陈木子; 王璐; 张海禄; 李宛飞; 丁元晨

    2011-01-01

    应用ID、2D NMR实验技术(1H NMR、13C NMR、DEPT、1H-1H COSY、1H-13CHMQC、1 H-13C HMBC等)研究了靶向新药吉非替尼的结构,对其1 H NMR和13C NMR谱峰作了全归属,并讨论了F原子对吉非替尼的1 H、13C NMR的影响.%The 13C and 1H NMR chemical shifts of gefitinib were assigned using ID and 2D NMR techniques, including ' H-1 H COSY, gHMQC and gHMBC. The effects of 19F substitution on 1H and 13C NMR spectra of the compound were investigated.

  5. Short-term effects of supplementary feeding with enteral nutrition via jejunostomy catheter on post-gastrectomy gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    WU Quan; YU Jian-chun; KANG Wei-ming; MA Zhi-qiang

    2011-01-01

    Background Most gastric cancer patients who undergo gastrectomy develop malnutrition.It is,therefore,crucial to establish an effective means to provide nutrition for these patients.To perform home enteral nutrition (EN) to ensure adequate nutritional intake in gastric cancer patients,we placed a jejunostomy catheter during gastric surgery.Most patients showed improved nutritional status.Methods Twenty-nine inpatients at our hospital underwent radical gastrectomy and jejunostomy from December 2002 to December 2007 and were designated as the jejunostomy group,and 32 matched patients without a jejunostomy tube were designated as the tube-free group.The jejunostomy group was treated with EN from 72 hours to 3 months postoperatively.The tube-free group did not receive EN.Data including preoperative and postoperative body weight,body mass index (BMI),nutrition risk screening (NRS) score,Karnofsky performance score (KPS),and laboratory biochemical indicators were documented respectively and compared.Results Compared with preoperative week 1,both groups showed decreased body weight and BMI at 3 months postoperatively.The weight loss in the jejunostomy group ((7.1±3.3) kg) was significantly less than that in the tube-free group ((9.9±3.1) kg).Similarly,BMI decreased by (2.4+1.0) kg/m2 in the jejunostomy group,which was significantly less than in the tube-free group ((3.2±0.9) kg/m2).The number of patients with postoperative NRS ≥3 was decreased in the jejunostomy group,but was increased in the tube-free group,and this difference was significant.There were no significant differences between the two groups in total lymphocyte count,hemoglobin,albumin and prealbumin,and adverse drug effects.Conclusions Short-term (3 months) EN supplementation via jejunostomy tube can reduce the risk of malnutrition and weight loss,and improve tolerance of chemotherapy.Tube feeding is reliable for achieving these goals because it is not important whether or not the patients have appetites.

  6. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  8. The mucin MUC4 is a transcriptional and post-transcriptional target of K-ras oncogene in pancreatic cancer. Implication of MAPK/AP-1, NF-κB and RalB signaling pathways.

    Science.gov (United States)

    Vasseur, Romain; Skrypek, Nicolas; Duchêne, Belinda; Renaud, Florence; Martínez-Maqueda, Daniel; Vincent, Audrey; Porchet, Nicole; Van Seuningen, Isabelle; Jonckheere, Nicolas

    2015-12-01

    The membrane-bound mucinMUC4 is a high molecularweight glycoprotein frequently deregulated in cancer. In pancreatic cancer, one of the most deadly cancers in occidental countries, MUC4 is neo-expressed in the preneoplastic stages and thereafter is involved in cancer cell properties leading to cancer progression and chemoresistance. K-ras oncogene is a small GTPase of the RAS superfamily, highly implicated in cancer. K-ras mutations are considered as an initiating event of pancreatic carcinogenesis and K-ras oncogenic activities are necessary components of cancer progression. However, K-ras remains clinically undruggable. Targeting early downstream K-ras signaling in cancer may thus appear as an interesting strategy and MUC4 regulation by K-ras in pancreatic carcinogenesis remains unknown. Using the Pdx1-Cre; LStopL-K-rasG12D mouse model of pancreatic carcinogenesis, we show that the in vivo early neo-expression of the mucin Muc4 in pancreatic intraepithelial neoplastic lesions (PanINs) induced by mutated K-ras is correlated with the activation of ERK, JNK and NF-κB signaling pathways. In vitro, transfection of constitutively activated K-rasG12V in pancreatic cancer cells led to the transcriptional upregulation of MUC4. This activation was found to be mediated at the transcriptional level by AP-1 and NF-κB transcription factors via MAPK, JNK and NF-κB pathways and at the posttranscriptional level by a mechanism involving the RalB GTPase. Altogether, these results identify MUC4 as a transcriptional and post-transcriptional target of K-ras in pancreatic cancer. This opens avenues in developing new approaches to target the early steps of this deadly cancer.

  9. Stereotactic Body Radiotherapy as Monotherapy or Post-External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

    Energy Technology Data Exchange (ETDEWEB)

    Jabbari, Siavash [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Weinberg, Vivian K. [Biostatistics and Computational Biology Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California (United States); Kaprealian, Tania; Hsu, I-Chow; Ma Lijun; Chuang, Cynthia; Descovich, Martina; Shiao, Stephen [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California San Francisco, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Department of Urology, University of California San Francisco, San Francisco, California (United States); Gottschalk, Alexander R., E-mail: AGottschalk@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States)

    2012-01-01

    Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. Patients and Methods: To date, 38 patients have been treated with SBRT at University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy Multiplication-Sign 4 fractions), and 18 were treated with SBRT boost (9.5 Gy Multiplication-Sign 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost

  10. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  11. Research Progress on Resistance Mechanisms of Epidermal Growth Factor Receptor 
Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuan LI

    2012-02-01

    Full Text Available With a greater understanding of tumor biology, novel molecular-targeted strategies that block cancer progression pathways have been evaluated as a new therapeutic approach for treating non-small cell lung cancer (NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer in some populations of NSCLC patients. However, the efficacy of EGFR-TKIs is limited by either primary (de novo or acquired resistance after therapy. This review will focus on recently identified mechanisms of primary and acquired resistance to EGFR TKIs and strategies currently being employed to overcome resistance.

  12. Impact of post-operative radiation on coronary arteries in patients of early breast cancer: A pilot dosimetric study from a tertiary cancer care center from India

    Directory of Open Access Journals (Sweden)

    S Roy

    2015-01-01

    Full Text Available Background: The significant impact of postoperative radiotherapy (PORT on cardiac morbidity in patients of early breast cancer (EBC undergoing breast-conserving surgery has been shown in different studies. The present study was conducted to assess the impact of surgery and the side of involvement on radiation dose to left anterior descending artery (LAD and Left circumflex coronary artery (LCx. Materials And Methods: Totally, 58 patients of EBC were randomly chosen for this dosimetric study and planned with tangential field technique without intensity modulation (IM. Heart, LAD, and LCx (n = 55 were contoured. Dose volume histograms were analyzed to determine the Dmax (maximum dose and Dmean (mean dose of LAD and LCx. Student's t-test was used for comparative analysis of the means. Results: The mean Dmax of LAD for left (L EBC was 3.17 Gray (Gy while for right (R EBC it was 0.86 Gy (P = 0.007; 95% C.I, 1.14–3.48. The mean Dmean of LAD for L-EBC and R-EBC were 1.97 Gy and 0.79 Gy, respectively (P = 0.029; 95% C.I, 0.77–1.60. The mean-Dmax of LCx for patients with L-EBC (2.9 Gy; range: 1.2–4.35 Gy was statistically higher than that for R-EBC (1.3 Gy; range: 0.7–3.2 Gy (P = 0.045. The mean-Dmean of LCx for L-EBC (2.1 Gy; range: 0.6–3.6 Gy was also significantly higher than that of L-EBC (0.9 Gy; range: 0.7–2.1 Gy (P = 0.03. There was no significant impact of the pattern of surgery on LAD dose, but significance was noted for LCx dose parameters (P = 0.04 and 0.08 for m-Dmax and m-Dmean of LCx. Conclusion: This pilot dosimetric study confirms the assumption that patients with left-sided EBC are at higher risk of developing long-term cardiac morbidity when treated with PORT due to increased dose to LAD.

  13. Identification of EGFR kinase domain mutations among lung cancer patients in China: implication for targeted cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Bao Ming QIN; Xiao CHEN; Jing De ZHU; Duan Qing PEI

    2005-01-01

    Lung cancer is one of the leading causes of death with one of the lowest survival rates. However, a subset of lung cancer patients who are of Asian origin and carry somatic mutations in epidermal growth factor receptor or EGFR have responded remarkable well to two tyrosine kinase inhibitors, gefitinib and erlotinib. While EGFR mutation profiles have been reported from Japan, South Korea, and Taiwan, there is no such report from mainland of China where the largest pool of patients reside. In this report, we identified ten somatic mutations from a total of 41 lung cancer patients in China. Among them, seven mutations were found in 17 adenocarcinomas. In contrast to previous reports, eight of these mutations are deletions in exon 19 and two of these deletions are homozygous. These results suggest that a large portion of Chinese adenocarcinoma patients could benefit from gefitinib or erlotinib. This unique mutation profile provides a rationale to develop the next generation of EGFR inhibitors more suitable for the Chinese population.

  14. Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

    Directory of Open Access Journals (Sweden)

    Toshihide Nishimura

    2012-01-01

    Full Text Available An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib and TARCEVA (Erlotinib treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care.

  15. 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

  16. Long-Term Treatment with Erlotinib for EGFR Wild-Type Non-Small Cell Lung Cancer: A Case Report.

    Science.gov (United States)

    Polychronidou, Genovefa; Papakotoulas, Pavlos

    2013-01-01

    The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are known to have greater efficacy in EGFR mutation-positive non-small cell lung cancer (NSCLC), although erlotinib also has activity in wild-type disease. We report the successful long-term maintenance treatment of a patient with EGFR wild-type NSCLC with gefitinib and later erlotinib. The patient (male; 44 years old; smoker) was diagnosed with EGFR wild-type NSCLC after computer tomography had revealed a mediastinal mass, and histology and mutation testing had identified the tumor as an EGFR wild-type grade 3 adenocarcinoma. The patient received multiple rounds of chemotherapy, followed by gefitinib maintenance (3 years). Later on, he received erlotinib maintenance and developed a persistent rash (grade 1/2) that lasted throughout the treatment. The patient's condition has remained stable on erlotinib for more than 5 years, with no evidence of progression. We describe the patient's disease course and treatment in the context of EGFR TKI therapy and the prognostic factors for long-term clinical outcomes of NSCLC, including the development of erlotinib-induced rash.

  17. 吉非替尼/厄洛替尼致间质性肺疾病患者的临床特点及预后%Clinical characteristics and prognosis of patients with interstitial lung disease induced by gefitinib or erlotinib

    Institute of Scientific and Technical Information of China (English)

    刘晓琦; 杨敏

    2015-01-01

    Objective To explore the clinical characteristics and prognosis in patients with interstitial lung disease( ILD ) induced by gefitinib or erlotinib. Methods "Epidermal growth factor receptor tyrosine kinase inhibitors" "gefitinib" "erlotinib" "interstitial lung disease" "case report",and corresponding Chinese vocabularies were selected as key words and PubMed,MEDLINE,Web of Science, CNKI,Wanfang databases,VIP and CBMdisc from January 2001 to April 2014 were searched. The case reports of ILD induced by gefitinib or erlotinib were collected,the patients' age,sex,pathologic diagnosis and staging,anamnesis,history of treatment,ILD occurrence time,clinical manifestations,treatments and outcome were recorded. Results A total of 40 reports involving 60 patients were entered. Fifty-nine cases were diagnosed as non-small cell lung cancer. Thirty-five( 58. 3%) patients were treated with gefitinib,34 of them were given 250mg/d and one was given 500 mg/d. Twenty-five(41. 7%)cases were treated with erlotinib 150 mg/d. The shortest occurrence time of ILD was one day after medication,the longest time was 210 days after medication. Thirty-three(55. 0%)patients developed ILD during 7-28 days after medication. The major clinical manifestations of ILD due to gefitinib and erlotinib were dyspnea,cough and fever. Ten(16. 7%),2(3. 3%)and 2(3. 3%)cases developed erythra,diarrhea and liver injury at the same time,respectively. The patients who were diagnosed as ILD were withdrawn immediately and treated with symptomatic and harmonic therapy. Thirty patientsˊclinical symptom and imaging features were improved 3-90 days( median 10 days)later. Thirty patients died 1-80 days( median 6 days)later. The patients who were diagnosed as ILD in less than 7 days after medication,had history of pulmonary fibrosis or radiation pneumonitis,and developed liver injury meanwhile(4,2,2,respectively)died. Conclusions The median time of ILD induced by gefitinib or erlotinib was 24 days( 1-210 days ). The

  18. SU-E-T-628: Predicted Risk of Post-Irradiation Cerebral Necrosis in Pediatric Brain Cancer Patients: A Treatment Planning Comparison of Proton Vs. Photon Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freund, D [Willis Knighton Cancer Center, Shreveport, LA (United States); Zhang, R; Sanders, M [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Newhauser, W [Louisiana State University, Baton Rouge, LA (United States)

    2015-06-15

    Purpose: Post-irradiation cerebral necrosis (PICN) is a severe late effect that can Result from brain cancers treatment using radiation therapy. The purpose of this study was to compare the treatment plans and predicted risk of PICN after volumetric modulated arc therapy (VMAT) to the risk after passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT) in a cohort of pediatric patients. Methods: Thirteen pediatric patients with varying age and sex were selected for this study. A clinical treatment volume (CTV) was constructed for 8 glioma patients and 5 ependymoma patients. Prescribed dose was 54 Gy over 30 fractions to the planning volume. Dosimetric endpoints were compared between VMAT and proton plans. The normal tissue complication probability (NTCP) following VMAT and proton therapy planning was also calculated using PICN as the biological endpoint. Sensitivity tests were performed to determine if predicted risk of PICN was sensitive to positional errors, proton range errors and selection of risk models. Results: Both PSPT and IMPT plans resulted in a significant increase in the maximum dose and reduction in the total brain volume irradiated to low doses compared with the VMAT plans. The average ratios of NTCP between PSPT and VMAT were 0.56 and 0.38 for glioma and ependymoma patients respectively and the average ratios of NTCP between IMPT and VMAT were 0.67 and 0.68 for glioma and ependymoma plans respectively. Sensitivity test revealed that predicted ratios of risk were insensitive to range and positional errors but varied with risk model selection. Conclusion: Both PSPT and IMPT plans resulted in a decrease in the predictive risk of necrosis for the pediatric plans studied in this work. Sensitivity analysis upheld the qualitative findings of the risk models used in this study, however more accurate models that take into account dose and volume are needed.

  19. Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

    2016-03-01

    Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

  20. Cancer

    Science.gov (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  1. Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Ni; Li Zhang

    2016-01-01

    Objective: To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources: An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection: The search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)","epidemiology", "EGFR", "TKIs", and "optimal selection".Results: As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions: Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with

  2. La Poste

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ The French Post Office has issued ten commemorative envelopes bearing original images depicting CERN and its history. This special fiftieth anniversary collector's edition will be available on the French Post Office (« La Poste ») stand at the Open Day on 16 October, in the CMS experiment hall at Cessy. Information for collectors: a pictorial postmark and date stamp have been specially designed and produced for the occasion with the assistance of CERN's graphics team. Sending a philatelic souvenir is a great way to commemorate the Open Day, so La Poste will be setting up a large post-box for that very purpose next to its stand. A perfect way to send images of CERN all around the world...

  3. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  4. Closing the loop: an interactive action-research conference format for delivering updated medical information while eliciting Latina patient/family experiences and psychosocial needs post-genetic cancer risk assessment.

    Science.gov (United States)

    Macdonald, Deborah J; Deri, Julia; Ricker, Charité; Perez, Martin A; Ogaz, Raquel; Feldman, Nancy; Viveros, Lori A; Paz, Benjamin; Weitzel, Jeffrey N; Blazer, Kathleen R

    2012-09-01

    A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43 years. Among patients, 73 % had a breast cancer history; 85 % had BRCA testing (49 % BRCA+). Nearly all (96 %) attendees completed the conference surveys and ARS queries; ≥48 % participated in interactive discussions. Most (95 %) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research.

  5. 乳腺癌患者术后化疗期创伤后成长的质性研究%A qualitative research on post traumatic growth of breast cancer patients during chemotherapy period after operation

    Institute of Scientific and Technical Information of China (English)

    李秀娟; 张平; 李晓燕; 宋旭红

    2012-01-01

    目的 了解女性乳腺癌患者术后化疗期创伤后成长状况.方法 采用现象学研究的方法对10例女性乳腺癌术后化疗期患者进行访谈,现场记录资料,并运用Claizzi分析程序进行分析.结果 乳腺癌术后化疗期患者负性心理和与负性事件抗争的意识并存,在与疾病抗争中萌芽信心,并开始重新审视生命和健康,规划未来,积极应对.结论 乳腺癌术后化疗期患者存在明显的创伤后成长,挖掘创伤后患者正性的心理资源成为乳癌患者心理护理的新视角.%Objective To understand ihe experience of post traumatic growth of breast cancer patients during chemotherapy period after operation. Methods Phenomenology method was used in the study. Ten breast cancer patients during chemotherapy period after operation were interviewed. Data were recorded in the interview and analyzed by Claizzi program. Results Breast cancer patients during chemotherapy period after operation had both of negative mental problems and fight for negative events. During the course of fighting with disease, the patients developed their confidence and began to rethink life and health ,plan the future and cope positively. Conclusion There are obvious post traumatic growth in breast cancer patients during chemotherapy period after operation. Exploring the positive psychological resources of breast cancer patients is a new view for psychological nursing.

  6. Highly sensitive HPLC-DAD method for the assay of gefitinib in patient plasma and cerebrospinal fluid: application to a blood-brain barrier penetration study.

    Science.gov (United States)

    Fang, Luo; Song, Yu; Weng, Xu; Li, Fanzhu; Xu, Yaping; Lin, Nengming

    2015-12-01

    The quantification of intracranial gefitinib (GEF) exposure is limited owing to the sensitivity of analytical equipment. Although mass spectrometry (MS) is the preferred method because of its high sensitivity, the equipment is not available in many laboratories, especially in developing Asian countries. In this paper, we developed a highly sensitive high performance liquid chromatography-diode array detector (HPLC-DAD) method for the assay of GEF in human cerebrospinal fluid (CSF) and plasma. GEF was extracted from CSF and plasma by solid-phase extraction and liquid-liquid extraction, respectively. The chromatographic separation was performed on a C18 column with gradient elution of 0.1% triethylamine solution and acetonitrile, then finally detected at 344 nm. This method was validated and proved to be highly sensitive with a lower limit of quantitation value of 0.11 ng/mL in CSF and 11 ng/mL in plasma. The blood-brain barrier penetration ratio of GEF ranged from 1.48 to 2.41%. This method provides a reliable MS-independent solution for the quantitation of GEF in patients' CSF and plasma.

  7. Adjuvant post-operative radiotherapy vs radiotherapy plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer. A phase III randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Cafiero, F.; Gipponi, M.; Di Somma, C. [Istituto Nazionale per la Ricerca sul Cancro, Geneo (Italy). Istituto di Oncologia Clinica] [and others

    1995-08-01

    Loco-regional and distant relapses contribute to impair the outcome of rectal cancer patients. As to the former, either pre-or post-operative radiation therapy (RT) significantly reduce loco-regional recurrence; post-operative chemotherapy (CT), alone or in different combinations with RT, is effective in improving both disease-free survival and survival. However, many drawbacks still exist regarding the method of RT delivery as well as the toxicity of combination adjuvant chemotherapy. The aim of this trial is to assess the effectiveness and toxicity of adjuvant post-operative RT vs combined RT and CT (5-FU plus levamisole) in patients with TNM stage II-III resectable rectal cancer (pT3-4, pN0, M0; pT1-4, pN1-3, M0). The primary endpoint is overall survival; secondary endpoints are disease-free survival rate of loco-regional recurrence, and treatment-related toxicity/morbidity. (author).

  8. Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer

    OpenAIRE

    Phak, Jeong Hoon; Kim, Hun Jung; Kim, Woo Chul

    2015-01-01

    Background Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer. Methods A total of 77 patients with localized prostate cancer [T-stage, T1–T3; Gleason score (GS) 5–9; PSA 

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

    DEFF Research Database (Denmark)

    Midtgaard, Julie

    2013-01-01

    Sedentary behaviour and reduced exercise capacity are potential persisting effects of anti-cancer therapy that may predispose to serious health conditions. It is well-established that physical exercise may prevent some of these problems. However, the extent to which cancer survivors are able...

  10. Prevalence and risk of depressive symptoms 3-4 months post-surgery in a nationwide cohort study of Danish women treated for early stage breast-cancer

    DEFF Research Database (Denmark)

    Christensen, Søren; Zachariae, Robert; Jensen, Anders Bonde

    2009-01-01

    breast cancer during the 2 1/2 year study period. Of these, 3343 women (68%) participated in a questionnaire study 12-16 weeks following surgery. Depressive symptoms (Beck's Depression Inventory II) and health-related behaviors were assessed by questionnaire. The Danish Breast Cancer Cooperative Group......BACKGROUND: Elevated levels of depressive symptoms are generally found among cancer patients, but results from existing studies vary considerably with respect to prevalence and proposed risk factors. PURPOSE: To study the prevalence of depressive symptoms and major depression 3-4 months following...... surgery for breast cancer, and to identify clinical risk factors while adjusting for pre-cancer sociodemographic factors, comorbidity, and psychiatric history. PATIENTS AND METHODS: The study cohort consists of 4917 Danish women, aged 18-70 years, receiving standardized treatment for early stage invasive...

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

    Directory of Open Access Journals (Sweden)

    Yang CJ

    2016-03-01

    Full Text Available Chih-Jen Yang,1–4 Ming-Ju Tsai,2,4 Jen-Yu Hung,2,3 Ta-Chih Liu,3,5 Shah-Hwa Chou,3,6 Jui-Ying Lee,6 Jui-Sheng Hsu,3,7 Ying-Ming Tsai,1,2,4 Ming-Shyan Huang,2–4 Inn-Wen Chong2,3 1Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, 3Faculty of Medicine, College of Medicine, 4Graduate Institute of Medicine, College of Medicine, 5Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 6Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 7Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Increased evidences show that epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear.Patients and methods: We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy, and overall survival (OS2, the OS in salvage therapy were recorded.Results: Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this

  12. Estimated generic prices of cancer medicines deemed cost-ineffective in England: a cost estimation analysis

    Science.gov (United States)

    Hill, Andrew; Redd, Christopher; Gotham, Dzintars; Erbacher, Isabelle; Meldrum, Jonathan; Harada, Ryo

    2017-01-01

    Objectives The aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs. Setting This research was carried out in a non-clinical research setting using secondary data. Participants There were no human participants in the study. Four drugs were selected for the study: bortezomib, dasatinib, everolimus and gefitinib. These medications were selected according to their clinical importance, novel pharmaceutical actions and the availability of generic price data. Primary and secondary outcome measures Target costs for treatment were to be generated for each indication for each treatment. The primary outcome measure was the target cost according to a production cost calculation algorithm. The secondary outcome measure was the target cost as the lowest available generic price; this was necessary where export data were not available to generate an estimate from our cost calculation algorithm. Other outcomes included patent expiry dates and total eligible treatment populations. Results Target prices were £411 per cycle for bortezomib, £9 per month for dasatinib, £852 per month for everolimus and £10 per month for gefitinib. Compared with current list prices in England, these target prices would represent reductions of 74–99.6%. Patent expiry dates were bortezomib 2014–22, dasatinib 2020–26, everolimus 2019–25 and gefitinib 2017. The total global eligible treatment population in 1 year is 769 736. Conclusions Our findings demonstrate that affordable drug treatment costs are possible for novel cancer drugs, suggesting that new therapeutic options can be made available to patients and doctors worldwide. Assessing treatment cost estimations alongside cost-effectiveness evaluations is an important area of future research. PMID:28110283

  13. Association between the polymorphisms of angiotensin converting enzyme (Peptidyl-Dipeptidase A INDEL mutation (I/D and Angiotensin II type I receptor (A1166C and breast cancer among post menopausal Egyptian females

    Directory of Open Access Journals (Sweden)

    Rania Mohamed El Sharkawy

    2014-09-01

    Results: A statistically significant difference in AT1R A1166C SNP genotype frequencies was found among the studied groups. The patients group showed higher frequency of “CC” (2.9% vs 0% and “AC” (44.3% vs 24% and lower frequency of “AA” genotype (52.9% vs 76% than controls. The patients also showed significant higher frequency of allele “C” (25% vs 12% which was associated with increased breast cancer risk with an Odds ratio of 2.4444 (95% CI: 1.1967–4.9931. Testing the dominant model of inheritance revealed a statistically higher frequency of exposed genotypes “AC and CC” among the patients group (47.1% vs 24%, respectively; p = 0.013 with substantial increase in breast cancer risk among the exposed genotypes with an Odds ratio of 2.8243 (95% CI: 1.2679–6.2913. The present study demonstrated that (AC and CC genotypes of AT1R A1166C SNP and increased BMI can be considered as predictors for breast cancer risk among post menopausal Egyptian females. Results also revealed that A1166C SNP of AT1R gene and ACE/ID polymorphism could not be considered as predictors for breast cancer prognosis.

  14. A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

    Directory of Open Access Journals (Sweden)

    Chi-Tai Yeh

    2013-01-01

    Full Text Available Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs, was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA, was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

  15. Neuromedin B receptors regulate EGF receptor tyrosine phosphorylation in lung cancer cells

    Science.gov (United States)

    Moody, Terry W.; Berna, Marc J.; Mantey, Samuel; Sancho, Veronica; Ridnour, Lisa; Wink, David A.; Chan, Daniel; Giaccone, Giuseppe; Jensen, Robert T.

    2014-01-01

    Neuromedin B (NMB), a member of the bombesin family of peptides, is an autocrine growth factor for many lung cancer cells. The present study investigated the ability of NMB to cause transactivation of the epidermal growth factor (EGF) receptor in lung cancer cells. By Western blot, addition of NMB or related peptides to NCI-H1299 human non-small cell lung cancer (NSCLC) cells, caused phosphorylation of Tyr1068 of the EGF receptor. The signal was amplified using NCI-H1299 cells stably transected with NMB receptors. The transactivation of the EGF receptor or the tyrosine phosphorylation of ERK caused by NMB-like peptides was inhibited by AG1478 or gefitinib (tyrosine kinase inhibitors) and NMB receptor antagonist PD168368 but not the GRP receptor antagonist, BW2258U89. The transactivation of the EGF receptor caused by NMB-like peptides was inhibited by GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), or transforming growth factor (TGF)α antibody. The transactivation of the EGF receptor and the increase in reactive oxygen species caused by NMB-like peptides was inhibited by N-acetylcysteine (NAC) or Tiron. Gefitinib inhibited the proliferation of NCI-H1299 cells and its sensitivity was increased by the addition of PD168368. The results indicate that the NMB receptor regulates EGF receptor transactivation by a mechanism dependent on Src as well as metalloprotease activation and generation of reactive oxygen species. PMID:20388507

  16. [Importance of Post-Marketing Studies in Gathering of Clinical Evidences for Proper Usage of Anti-Cancer Drugs, and the StudyRequirements for Their Credibility].

    Science.gov (United States)

    Inagaki, Osamu

    2016-04-01

    Pharmaceutical companies recognize the importance of post-marketing studies because they are crucial in the generation of clinical evidences for the usage of new medicines. To generate clinical evidences, quality of post-marketing studies should be well controlled from view point of "ethical conduction" and "reliability of results". In addition, control of conflict of interest (COI) between researchers and industries is also indispensable and is requested for the transparency of the studies. Japan Pharmaceutical Manufacturers Association(JPMA)stresses its commitment to the progressof transparency in post-marketing studies.

  17. Loss of post-transcriptional regulation of DNMT3b by microRNAs: a possible molecular mechanism for the hypermethylation defect observed in a subset of breast cancer cell lines.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Coleman, William B

    2012-08-01

    A hypermethylation defect associated with DNMT hyperactivity and DNMT3b overexpression characterizes a subset of breast cancers and breast cancer cell lines. We analyzed breast cancer cell lines for differential expression of regulatory miRs to determine if loss of miR-mediated post-transcriptional regulation of DNMT3b represents the molecular mechanism that governs the overexpression of DNMT3b that drives the hypermethylation defect in breast cancer. MicroRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a, miR-148b) or are predicted (miR-26a, miR-26b, miR-203, miR-222) to regulate DNMT3b were examined among 10 hypermethylator and 6 non-hypermethylator breast cancer cell lines. Hypermethylator cell lines express diminished levels of miR-29c, miR-148a, miR-148b, miR-26a, miR-26b, and miR-203 compared to non-hypermethylator cell lines. miR expression patterns correlate inversely with methylation-sensitive gene expression (r=-0.66, p=0.0056) and directly with the methylation status of these genes (r=0.72, p=0.002). To determine the mechanistic role of specific miRs in the dysregulation of DNMT3b among breast cancer cell lines, miR levels were modulated by transfection of pre-miR precursors for miR-148b, miR-26b, and miR-29c into hypermethylator cell lines (Hs578T, HCC1937, SUM185) and transfection of antagomirs directed against miR-148b, miR-26b, and miR-29c into non-hypermethylator cell lines (BT20, MDA-MB-415, MDA-MB-468). Antagomir-mediated knock-down of miR-148b, miR-29c, and miR-26b significantly increased DNMT3b mRNA in non-hypermethylator cell lines, and re-expression of miR-148b, miR-29c, and miR-26b following transfection of pre-miR precursors significantly reduced DNMT3b mRNA in hypermethylator cell lines. These findings strongly suggest that: i) post-transcriptional regulation of DNMT3b is combinatorial, ii) diminished expression of regulatory miRs contributes to DNMT3b overexpression, iii) re-expression of regulatory miRs reduces DNMT3b m

  18. Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What's new?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.

  19. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  20. Monitoring post

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg; Jespersen, Andreas Maaløe

    2013-01-01

    This blog reports on the rumour that White House considers establishing a nudge unit similar to the UK Behavioural Insights Team. Given The Nudging Networks purpose and the work of the iNudgeYou-team this post is updated continuously to follow the US debate as it unfolds. Which issues are raised......? How is the debate different from the one in the UK? And how does our work relate to the issues raised? The post has already been referenced in several US media, including US News....

  1. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

    DEFF Research Database (Denmark)

    Pirker, Robert; Herth, Felix J F; Kerr, Keith M;

    2010-01-01

    Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR...... tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker......-directed therapy only slowly emerges for the subset of NSCLC patients most likely to benefit: those with EGFR mutations....

  2. Advances in the management of acquired resistance to EGFR-TKI in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Fei Zhou; Caicun Zhou

    2015-01-01

    Drugs that specifical y target the tyrosine kinase domain of epidermal growth factor receptor (EGFR), such as erlotinib or gefitinib, have exhibited striking ef icacy in non-smal cel lung cancer (NSCLC) patients har-boring activating EGFR mutations. However, acquired resistance inevitably develops and remains a serious barrier for the successful management of patients with this disease. Multiple mechanisms are reportedly involved in the process of acquired resistance, which provide new insights into the management of EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance. Here, we provide an overview of the emerging treatment approaches for patients with EGFR-TKI resistance.

  3. Determination of antibody to Streptococcus mutans from radiation-induced xerostomia patients. Agglutination activity against cariogenic microorganisms, active immunoglobulin classes, and post-irradiation caries activity in cancer patients. Final report 15 jul 77-14 apr 79

    Energy Technology Data Exchange (ETDEWEB)

    Brown, L.R.; O' Neill, P.A.; Dreizen, S.

    1979-07-01

    The relationship between specific agglutination (Ag) and caries activity during 30 month post radiation was assessed in 36 head and neck cancer patients. Ag titers in 444 saliva and 481 serum samples from these patients and 16 noncancer controls were determined against formalinized cellular antigens of Streptococcus mutans (Sm), Streptococcus sanguis (Ss), Streptococcus mitis, Lactobacillus fermenti (Lf), and Lactobacillus casei. Saliva IgA and IgG levels and Ag titers were significantly higher in cancer patients than in noncancer controls. Post radiation-induced xerostomic changes in saliva IgA reflected changes in specific Ag against oral microbes, particularly Sm serotype c. Patients with high saliva IgA levels had significantly higher saliva Ag titers to Sm, Ss and Lf, lower plaque Sm counts and lower caries activity than patients with low saliva IgA levels. Serum Ag titers, however, showed no significant relationship with either serum Ig levels, microbial counts or caries activity. Chromatographic separation of Ig classes showed that Ag activity in saliva stemmed mainly from secretory IgA. Most serum Ag activity was found in regions corresponding to IgG and 7S IgA.

  4. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Latifi, K; Hoffe, S; Moros, E [Moffitt Cancer Center, Tampa, FL (United States); Saeed, Nadia [Brwon University, Providence, RI (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Shridhar, R [Florida Hospital, Orlando, FL (United States)

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  5. Impact of Bone-targeted Therapies in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer Patients Treated with Abiraterone Acetate: Post Hoc Analysis of Study COU-AA-302

    Science.gov (United States)

    Saad, Fred; Shore, Neal; Van Poppel, Hendrik; Rathkopf, Dana E.; Smith, Matthew R.; de Bono, Johann S.; Logothetis, Christopher J.; de Souza, Paul; Fizazi, Karim; Mulders, Peter F.A.; Mainwaring, Paul; Hainsworth, John D.; Beer, Tomasz M.; North, Scott; Fradet, Yves; Griffin, Thomas A.; De Porre, Peter; Londhe, Anil; Kheoh, Thian; Small, Eric J.; Scher, Howard I.; Molina, Arturo; Ryan, Charles J.

    2016-01-01

    Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Intervention Patients were grouped by concomitant BTT use or no BTT use. Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy

  6. Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

    Directory of Open Access Journals (Sweden)

    Fosså Sophie D

    2007-07-01

    Full Text Available Abstract Background The ATM protein is activated as a result of ionizing radiation, and genetic variants of the ATM gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for ATM mutations have been reported to have an increased risk of malignancy, especially breast cancer. Materials and methods Norwegian breast cancer patients (272 treated with radiation (252 of which were evaluated for radiation-induced adverse side effects, 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR were screened for sequence variations in all exons of the ATM gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC followed by sequencing to determine the nature of the variant. Results and Conclusion A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala substitution in exon 11 (P-value 0.055 between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06. Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the ATM gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour

  7. Gynecologic Malignancies Post-LeFort Colpocleisis

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2014-01-01

    Full Text Available Introduction. LeFort colpocleisis (LFC is a safe and effective obliterative surgical option for older women with advanced pelvic organ prolapse who no longer desire coital activity. A major disadvantage is the limited ability to evaluate for post-LFC gynecologic malignancies. Methods. We present the first case of endometrioid ovarian cancer diagnosed after LFC and review all reported gynecologic malignancies post-LFC in the English medical literature. Results. This is the second reported ovarian cancer post-LFC and the first of the endometrioid subtype. A total of nine other gynecologic malignancies post-LFC have been reported in the English medical literature. Conclusions. Gynecologic malignancies post-LFC are rare. We propose a simple 3-step strategy in evaluating post-LFC malignancies.

  8. Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    2017-02-01

    Full Text Available Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1, chloroquine (CQ and 3-methyladenine (3-MA were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8 assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating

  9. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer

    NARCIS (Netherlands)

    van Ginkel, Joost H.; de Leng, Wendy W J; de Bree, Remco; van Es, Robert J J; Willems, Stefan M.

    2016-01-01

    Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post tr

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

    DEFF Research Database (Denmark)

    Lykke, Malene Risager; Nielsen, Tommy Kjaergaard; Ebbensgaard, Nanna Andersen;

    2015-01-01

    : Fluorescence cystoscopy using hexyl-aminolevulinate and post-TURB chemoprophylaxis using mitomycin C were simultaneously introduced in an effort to reduce the recurrence of NMIBC. In total, 190 consecutive patients were enrolled over a 2 year period and followed as the intervention group; 216 patients treated...

  11. The Effects of Dinner-to-Bed Time and Post-Dinner Walk on Gastric Cancer Across Different Age Groups: A Multicenter Case-Control Study in Southeast China.

    Science.gov (United States)

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

    2016-04-01

    Gastric cancer (GC) remains a major killer throughout the world. Despite the dramatic decrease in GC over the last century, its etiology has not yet been well characterized. This study investigated the possible independent and combined effects of the dinner-to-bed time and post-dinner walk on the risk for GC across different age groups. A population-based, case-control study was conducted in southeast China, including 452 patients with GC and 465 age-, race-, and gender-matched controls. A self-designed questionnaire was used to collect information on demographic characteristics, dinner-to-bed time, post-dinner walk, and other behavioral factors. Conditional logistic regression models were used to estimate the effects of the dinner-to-bed time and post-dinner walk as well as their joint effect on the risk for GC across different age groups. Individuals with dinner-to-bed time time was, the higher was the risk for GC (Ptrend time and post-dinner walk on GC risk was detected (AOR = 1.862, 95% CIs = 1.584-3.885, synergy index [SI] = 2.654, 95% CIs = 2.27-3.912). Participants with dinner-to-bed time times likely to suffer from GC (AOR = 7.401, 95% CIs = 4.523-13.16) than those with dinner-to-bed time ≥4 hours who took such walk. The risk of GC due to dinner-to-bed time time 55 years old.

  12. Protocol for a pre-implementation and post-implementation study on shared decision-making in the surgical treatment of women with early-stage breast cancer

    NARCIS (Netherlands)

    Savelberg, W.; Moser, A.; Smidt, M.; Boersma, L.; Haekens, C.; Weijden, T. van der

    2015-01-01

    BACKGROUND: The majority of patients diagnosed with early-stage breast cancer are in a position to choose between having a mastectomy or lumpectomy with radiation therapy (breast-conserving therapy). Since the long-term survival rates for mastectomy and for lumpectomy with radiation therapy are comp

  13. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Tejpal [Tata Memorial Centre, Department of Radiation Oncology, Kharghar, Navi Mumbai (India); Tata Memorial Centre, Epidemiology Clinical Trials Unit-Clinical Research Secretariat, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai (India); Master, Zubin; Murthy, Vedang [Tata Memorial Centre, Department of Radiation Oncology, Kharghar, Navi Mumbai (India); Kannan, Sadhana [Tata Memorial Centre, Epidemiology Clinical Trials Unit-Clinical Research Secretariat, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai (India); Agarwal, Jai Prakash; Ghsoh-Laskar, Sarbani; Budrukkar, Ashwini [Tata Memorial Hospital, Department of Radiation Oncology, Mumbai (India); Rangarajan, Venkatesh [Tata Memorial Hospital, Bio-Imaging Unit, Mumbai (India)

    2011-11-15

    Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC). A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression. A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7-85.2%), 87.5% (85.2-89.5%), 58.6% (52.6-64.5%) and 95.1% (93.5-96.5%), respectively. Similar estimates for the neck were 72.7% (66.6-78.2%), 87.6% (85.7-89.3%), 52.1% (46.6-57.6%) and 94.5% (93.1-95.7%), respectively. Scans done {>=}12 weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate. The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy. (orig.)

  14. SUSPICIOUS POST

    CERN Multimedia

    Relations with the Host States Service

    2001-01-01

    If you receive a suspicious letter or package in the post, please do not open it and contact the Fire Brigade Tel. 74444. They will contact the CERN Medical Service. This is especially important in today's current situation with regard to the Anthrax scare. For further information, the Permanent Mission of Switzerland to the International Organisations in Geneva recommends the following web sites:   http://www.admin.ch/ch/f/cf/brennpunkt/03.html http://www.who.int/emc-documents/zoonoses/whoemczdi986c.html

  15. Research on Upper Extremity Edema Post Breast Cancer Operation%乳腺癌术后上肢水肿研究现状

    Institute of Scientific and Technical Information of China (English)

    姚礼珑; 曹文兰

    2014-01-01

    目前乳腺癌的治疗方法有手术、放射治疗、化学治疗、内分泌治疗和靶向治疗等,综合治疗方法的逐渐规范使乳腺癌患者的生存状况得到改善[1],对于早期乳腺癌手术为其首选的治疗方法,结合术后辅助放射治疗。乳腺癌手术多对腋窝淋巴结进行清扫,影响上肢淋巴回流,上肢淋巴水肿是乳腺癌术后级放射治疗后最常见的并发症之一,文献报道其发生率约为6%~14%。乳腺癌术后引起的上肢水肿严重影响患肢的正常功能,造成患者生活不便,生存质量下降。本文将对乳腺癌术后引起的上肢水肿研究现状进行总结。%Breast cancer is one of the most common malignant tumors in current world, which is the first cause of cancer death in women[1] .At present the treatment of breast cancer are surgery, radiotherapy, chemotherapy and endocrine treatment and targeted thera-py, etc., and the gradually standardized comprehensive treatment method has improved the condition of patients with breast cancer.Up-per limb lymphedema is one of the most common complications after breast cancer, whose reported incidence rate is about 6%to 14%. It affects the normal function of sick limb seriously, causing inconvenience for patients and lowering the quality of life.This article sum-marizes the research status on upper extremity edema caused by breast cancer and postoperative radiotherapy.

  16. Chronic myelomonocytic leukemia blast crisis in a patient with advanced non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.

    Science.gov (United States)

    Ogata, Hiroaki; Okamoto, Isamu; Yoshimoto, Goichi; Obara, Teppei; Ijichi, Kayo; Iwama, Eiji; Harada, Taishi; Akashi, Koichi; Nakanishi, Yoichi

    2017-03-01

    A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis. Physicians should be aware of such risks and monitor EGFR-TKI-treated patients with myeloid neoplasms accordingly.

  17. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation.

    Science.gov (United States)

    Lekovic, Gregory; Drazin, Doniel; Mak, Albert C; Schwartz, Marc S

    2016-01-07

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.

  18. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas Hg

    2011-06-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician's discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account.

  19. Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling.

    Science.gov (United States)

    Guo, Huabei; Nagy, Tamas; Pierce, Michael

    2014-11-01

    Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression.

  20. Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Eunjin Jwa

    Full Text Available The locoregional recurrence (LRR rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1-2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT.In total, 390 patients with pT1-2N0M0 (n = 307 and pT1-2N1M0 (n = 83 breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.After a median follow-up period of 5.6 years (range, 0.6-11.3 years, 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01 and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04 were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03 was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

  1. Nursing of post - operative respiratory failure in aged patients with lung cancer by using mechanical ventilation%机械通气治疗老年肺癌术后合并呼吸衰竭的护理体会

    Institute of Scientific and Technical Information of China (English)

    叶萍; 王红丽; 束燕; 陈静; 周莉莉; 余静

    2011-01-01

    Objective To explore the nursing of post- operative respiratory failure in aged patients with lung cancer using mechanical ventilation. Methods The clinical data of 18 aged patients with post- operative respiratory failure from March 2004 to December 2009 were analyzed retrospectively. They were all treated with mechanical ventilation, control pulmonary infection and nutrition support. Results Sixteen cases were cured(88.9% ), 1 case died and 1 case left hospital.Conclusion The aged patients with post - operative respiratory failure should be treated with mechanical ventilation in time. Modes of the ventilation should be appropriate. Nutrition support, the usage of antibiotics in treating primary should be emphasized. Early treatment can reduce mortality of respiratory failure.%目的 探讨老年肺癌术后合并急性呼吸衰竭患者早期应用呼机械通气治疗的护理经验.方法 回顾分析2004年3月至2009年12月本院老年肺癌术后合并呼吸衰竭18例临床资料,均行机械通气,同时控制肺部感染和给予营养支持.结果 16例治愈(88.9%),1例死亡,1例自动出院.结论 老年肺癌术后合并呼吸衰竭,应早期给予机械通气治疗,合理调整参数,注意无菌操作,加强护理,同时应用有效抗生素和营养支持.早期积极治疗有望降低病死率.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    with PWT. The dose to the internal mammary nodes (IMN) was not satisfactory for five of the seven patients for 3F, whereas only two of the seven patients had a minimum dose lower than 95% of the prescribed dose with PWT. Finally, the dose to the contralateral breast was increased when using PWT compared...... to 3F. It was concluded that PWT was an appropriate choice of technique for future radiation treatment of post-mastectomy patients. A working group was formed and guidelines for 3D planning were developed during a series of workshops where radiation oncologists and physicists from all radiotherapy...

  3. Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence

    Science.gov (United States)

    Gomes-Rochette, Neuza Felix; Souza, Letícia Soncini; Tommasi, Bruno Otoni; Pedrosa, Diego França; Fin, Irani do Carmo Francischetto; Vieira, Fernando Luiz Herkenhoff; Graceli, Jones Bernardes; Rangel, Letícia Batista Azevedo; Silva, Ian Victor

    2017-01-01

    Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010–2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations

  4. Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain

    Directory of Open Access Journals (Sweden)

    Koizumi Mitsuru

    2010-08-01

    Full Text Available Abstract Background Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs or survival (cause specific death, CSD, retrospectively. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis. Results Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not

  5. Lower limb compartment syndrome by reperfusion injury after treatment of arterial thrombosis post-laparoscopic radical hysterectomy and pelvic lymph node dissection for cervical cancer

    Science.gov (United States)

    Yeon, Jihee; Jung, Ye Won; Yang, Shin Seok; Kang, Byung Hun; Lee, Mina; Ko, Young Bok; Yang, Jung Bo; Lee, Ki Hwan

    2017-01-01

    Compartment syndrome is a clinical condition associated with decreased blood circulation that can lead to swelling of tissue in limited space. Several factors including lithotomy position, prolonged surgery, intermittent pneumatic compressor, and reperfusion after treatment of arterial thrombosis may contribute to compartment syndrome. However, compartment syndrome rarely occurs after gynecologic surgery. In this case, the patient was diagnosed as compartment syndrome due to reperfusion injury after treatment of arterial thrombosis, which occurred after laparoscopic radical hysterectomy and pelvic lymph node dissection for cervical cancer. Despite its rarity, prevention and identifying the risk factors of complication should be performed perioperatively; furthermore, gynecologist should be aware of the possibility of complications. PMID:28344966

  6. Post traumatic painful shoulder – a delayed clinical feature of upper lobe lung cancer in a 74 year-old male. - case report -

    Directory of Open Access Journals (Sweden)

    Oana-Cristina Arghir

    2014-02-01

    Full Text Available A 74 year old Caucasian man, presents with a 6 week history of right sided chest pain including traumatic related painful right shoulder. Shoulder minor contusion was diagnosed and partial managed by symptomatic treatment associated to rehabilitation. The pain was initially eased with nonsteroidal anti-inflammatory drug (NSAID use and finally changed worsening. He has evidence of moderate COPD on spirometry and has been commenced on inhalers. An invasive primitive adenocarcinoma lung cancer was confirmed by chest CT scan and lymphnode biopsy through mediastinoscopy

  7. Dosimetric results in implant and post-implant and low rate in brachytherapy prostate cancer with loose seeds and attached; Resultados dosimetricos en el implante y post-impante en braquiterapia de baja tasa en cancer de prostata con semillas sueltas y unidas

    Energy Technology Data Exchange (ETDEWEB)

    Juan-Senabre, X. J.; Albert Antequera, M.; Lopez-Tarjuelo, J.; Santos Serra, A.; Perez-Mestre, M.; Sanchez Iglesias, A. L.; Conde Moreno, A. J.; Gonzalez Vidal, V.; Beltran Persiva, J.; Muelas Soria, R.; Ferrer Albiach, C.

    2015-07-01

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

  8. Afatinib increases sensitivity to radiation in non-small cell lung cancer cells with acquired EGFR T790M mutation.

    Science.gov (United States)

    Zhang, Shirong; Zheng, Xiaoliang; Huang, Haixiu; Wu, Kan; Wang, Bing; Chen, Xufeng; Ma, Shenglin

    2015-03-20

    Afatinib is a second-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has shown a significant clinical benefit in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the potential therapeutic effects of afatinib combining with other modalities, including ionizing radiation (IR), are not well understood. In this study, we developed a gefitinib-resistant cell subline (PC-9-GR) with a secondary EGFR mutation (T790M) from NSCLC PC-9 cells after chronic exposures to increasing doses of gefitinib. The presence of afatinib significantly increases the cell killing effect of radiation in PC-9-GR cells harboring acquired T790M, but not in H1975 cells with de novo T790M or in H460 cells that express wild-type EGFR. In PC-9-GR cells, afatinib remarkable blocks baseline of EGFR and ERK phosphorylations, and causes delay of IR-induced AKT phosphorylation. Afatinib treatment also leads to increased apoptosis and suppressed DNA damage repair in irradiated PC-9-GR cells, and enhanced tumor growth inhibition when combined with IR in PC-9-GR xenografts. Our findings suggest a potential therapeutic impact of afatinib as a radiation sensitizer in lung cancer cells harboring acquired T790M mutation, providing a rationale for a clinical trial with combination of afatinib and radiation in NSCLCs with EGFR T790M mutation.

  9. Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Jixia Li

    2013-01-01

    Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

  10. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer.

    Science.gov (United States)

    Azzoli, Christopher G; Baker, Sherman; Temin, Sarah; Pao, William; Aliff, Timothy; Brahmer, Julie; Johnson, David H; Laskin, Janessa L; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pfister, David G; Piantadosi, Steven; Schiller, Joan H; Smith, Reily; Smith, Thomas J; Strawn, John R; Trent, David; Giaccone, Giuseppe

    2009-12-20

    The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

  11. Crizotinib induces PUMA-dependent apoptosis in colon cancer cells.

    Science.gov (United States)

    Zheng, Xingnan; He, Kan; Zhang, Lin; Yu, Jian

    2013-05-01

    Oncogenic alterations in MET or anaplastic lymphoma kinase (ALK) have been identified in a variety of human cancers. Crizotinib (PF02341066) is a dual MET and ALK inhibitor and approved for the treatment of a subset of non-small cell lung carcinoma and in clinical development for other malignancies. Crizotinib can induce apoptosis in cancer cells, whereas the underlying mechanisms are not well understood. In this study, we found that crizotinib induces apoptosis in colon cancer cells through the BH3-only protein PUMA. In cells with wild-type p53, crizotinib induces rapid induction of PUMA and Bim accompanied by p53 stabilization and DNA damage response. The induction of PUMA and Bim is mediated largely by p53, and deficiency in PUMA or p53, but not Bim, blocks crizotinib-induced apoptosis. Interestingly, MET knockdown led to selective induction of PUMA, but not Bim or p53. Crizotinib also induced PUMA-dependent apoptosis in p53-deficient colon cancer cells and synergized with gefitinib or sorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and therapeutic responses to crizotinib in xenograft models. These results establish a critical role of PUMA in mediating apoptotic responses of colon cancer cells to crizotinib and suggest that mechanisms of oncogenic addiction to MET/ALK-mediated survival may be cell type-specific. These findings have important implications for future clinical development of crizotinib.

  12. Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen

    Directory of Open Access Journals (Sweden)

    Chamnanphon M

    2013-05-01

    .90%, and *36 (1 of 114, 0.90%; the CYP2C19 variant alleles were *2 (27 of 114, 23.70% and *3 (6 of 114, 5.30%. Kaplan–Meier estimates showed significantly shorter disease-free survival in patients with homozygous TT when compared to those with heterozygous CT or homozygous CC at nucleotides 100C>T and 1039C>T (CYP2D6*10 post-menopausal (log-rank test; P = 0.046. They also had increased risk of recurrence, but no statistically significant association was observed (hazard ratio 3.48; 95% confidence interval 0.86–14.07; P = 0.080.Conclusion: The CYP2D6 and CYP2C19 polymorphisms were not involved in tamoxifen efficacy. However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. As the number of breast cancer patients was relatively small in this study, results should be confirmed in a larger group of prospective patients.Keywords: CYP2D6, CYP2C19, disease-free survival, tamoxifen, pharmacogenetics, breast cancer

  13. Analysis of survival risk on post-operative patients with rectal cancer excised%直肠癌患者术后生存风险分析

    Institute of Scientific and Technical Information of China (English)

    柳文蔚

    2013-01-01

    Objective To analyze survival risk factors on patients with rectal cancer excised, and to provide reference for clinical therapies of rectal cancer. Methods 72 clinical data of rectal cancer excised in Gangdao Hospital in Hainan Province from January 1998 to January 2007 were selected and analyzed retrospectively, survivorship curve and survival risk curve were drawn, survival time and survival rate were analyzed by Kaplan-Meier analysis; survival related factors and survival risk factors were screened and analyzed by chi-square test and Cox survival risk scale model. Results Operation modality, excision extent, tumor localization, TNM stage, tumor differentiation, and whether radiation and chemotherapy or not were found had relationship with survival time of patients by chi-square test (P < 0.05); xcision extent, tumor localization, TNM stage, and whether radiation and chemotherapy or not were the independent risk factors with the survival time by the Cox survival risk scale model. Conclusions It is useful to take sufficient evaluation and select reasonable treatment according to the main risk factors of survival time after colorectal cancer surgery, it also can enhance the treatment effect%目的 分析影响直肠癌患者术后生存的风险因素,为直肠癌的临床治疗提供参考.方法 选择海南省港岛医院1998年1月~2007年1月手术切除的直肠癌患者临床资料72例,绘制生存曲线及生存风险曲线,采用Kaplan-Meier分析患者生存时间及生存率,采用χ2检验及Cox生存风险比例模型筛选及分析患者生存相关因素及生存危险因素采用.结果手术治疗的直肠癌患者中位生存时间10~132个月,中位生存时间为51个月,伴随患者生存时间延长生存风险增加,χ2检验结果显示切除范围、肿瘤位置、肿瘤分期、肿瘤分化程度及是否放化疗与患者生存时间有关(P < 0.05);Cox生存风险比例模型分析显示,切除范围、肿瘤位置、肿瘤分期

  14. Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer.

    Science.gov (United States)

    Ruel, Ewa; Thomas, Samantha; Dinan, Michaela A; Perkins, Jennifer M; Roman, Sanziana A; Sosa, Julie Ann

    2016-06-01

    Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients negative surgical margins and multifocal disease (all p negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.

  15. PET/CT vs. non-contrast CT alone for surveillance 1-year post lobectomy for stage I non-small-cell lung cancer.

    Science.gov (United States)

    Dane, Bari; Grechushkin, Vadim; Plank, April; Moore, William; Bilfinger, Thomas

    2013-01-01

    (18)F-FDG PET/CT was compared with non-contrast chest CT in monitoring for recurrence 1-year after lobectomy of stage 1 non-small-cell lung cancer (NSCLC). For surveillance after treatment with curative intent, current (April 2012) National Comprehensive Cancer network guidelines recommend chest CT with or without contrast every 6-12 months for 2 years, then non-contrast chest CT annually. PET/CT is not currently indicated for routine follow-up. One hundred patients receiving surveillance PET/CT 1-year after lobectomy for the treatment of stage 1a or 1b NSCLC were included in the study. Exclusion criteria included the presence or interval diagnosis of a second malignancy, or surgical treatment more radical than single lobectomy. The non-contrast CT obtained from the 1-year PET/CT was interpreted by an experienced chest radiologist blinded to the PET/CT for evidence of recurrence using the following findings: pulmonary nodule, pleural effusion, pleural mass, adenopathy, and extrathoracic mass. The ecision about recurrence was made solely from the non-contrast CT without PET/CT findings. This was compared with the determination made with PET/CT. The reference standard for determination of recurrence was the multi-disciplinary tumor board who had access to all imaging and clinical data. Recurrence at 1 year was documented in 16 of 90 patients. All 16 recurrences were documented with PET/CT and 9 were found with non-contrast CT. Five of the 7 recurrences missed with non-contrast CT were extrathoracic metastases. Sensitivity of CT and PET/CT for recurrence was 56.3% and 100%, respectively (p = 0.015). Specificity of CT and PET/CT for recurrence was 95.9% and 93.2%, respectively (p = 0.62).

  16. 胃癌术后早期肠内营养的临床应用%Application of early enteral nutrition in post - operative patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    汪杰斌; 王晓亮

    2011-01-01

    Objective To investigate the feasibility, safety, fees and clinical effects of early enteral nutrition following gastric cancer operation. Methods 122 patients performed gastric cancer operation were randomly divided into early enteral nutrition group (cases) and parenteral nutrition group (cases). Results The time of flatus (46.98 ± 6.87,73.51 ± 11.53 ), bowel movement ( 83.89 ± 12.78,130.80 ± 22.93 ), and of hospital stay after operation in the EN group was significantly shorter than the PN group (9.79 ± 0.76,12.48 ± 1.46). In the first seven days after surgery, various parameter recovery rates in group EN were better than those in group PN. Also lower hospital costs in EN group(9548.17 ± 1754.86,14721.11 ± 2965.59). Conclusion Early enteral nutrition can modulate nutrition states, decrease the expense of nutritional support as well as the length of stay,in this EN is the best choice.%目的 探讨对胃癌患者术后早期肠内营养支持的方法、效果、费用及应用中注意事项.方法 通过对122例胃癌患者随机分组为早期肠内营养组(EN:n=61)和肠外营养组(PN:n=61)临床资料进行分析.结果 EN组术后在排气(46.98±6.87比73.51±11.53)、排便时间(83.89±12.78比130.80±22.93)、费用(9548.17±1754.86比14721.11±2965.59)及术后平均住院时间(9.79±0.76比12.48±1.46)、身体营养状况等方面均短于PN组,差异有统计学意义(P<0.05).结论 早期肠内营养能提高机体营养状况、缩短住院时间、减少住院费用,可作为最佳选择.

  17. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer.

    Science.gov (United States)

    van Ginkel, Joost H; de Leng, Wendy W J; de Bree, Remco; van Es, Robert J J; Willems, Stefan M

    2016-09-20

    Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post treatment surveillance. We retrospectively analyzed mutational hotspots using targeted next-generation sequencing (NGS) of 239 HNSCC tumor samples in order to examine the mutational profile of HNSCC. Furthermore, we assessed prevalence, co-occurrence, and synonymy of gene mutations in (matched) tumor samples. TP53 was found mutated the most frequent with mutation rates of up to 83% in all tumors, compared to mutation rates of between 0 and 21% of CDKN2A, PIK3CA, HRAS, CDK4, FBXW7 and RB1. Mutational co-occurrence predominantly existed between TP53 and PIK3CA, TP53 and CDKN2A, and HRAS and PIK3CA. Mutational synonymy between primary tumor and associated metastasis and recurrence was present in respectively 88% and 89%. TP53 mutations were concordantly mutated in 95% of metastases and in 91% of recurrences. This indicates TP53 mutations to be highly prevalent and concordant in primary tumors and associated locoregional metastases and recurrences. In turn, this provides ground for further investigating the use of TP53 mutations as diagnostic biomarkers in HNSCC patients.

  18. Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R.

    Science.gov (United States)

    Patel, Bhaumik B; Gupta, Deepshika; Elliott, Althea A; Sengupta, Vivek; Yu, Yingjie; Majumdar, Adhip P N

    2010-02-01

    Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence. The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells. Forty-eight-hour treatment of colon cancer HCT-116 and HT-29 cells with FOLFOX resulted in 60-70% survival, accompanied by a marked activation of insulin like growth factor-1 receptor (IGF-1R) and minor to moderate increase in epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT), cyclooxygenase-2 (COX-2) and cyclin-D1. However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1. More importantly, EGFR tyrosine kinase inhibitor gefitinib or attenuation of IGF-1R expression by the corresponding si-RNA caused a 30-60% growth inhibition of chemo-surviving HCT-116 cells. However, curcumin alone was found to be more effective than both gefitinib and IGF-1R si-RNA mediated growth inhibition of chemo-surviving HCT-116 cells and addition of FOLFOX to curcumin did not increase the growth inhibitory effect of curcumin. Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells.

  19. Tyrosine kinase blockers: new hope for successful cancer therapy.

    Science.gov (United States)

    Pytel, Dariusz; Sliwinski, Tomasz; Poplawski, Tomasz; Ferriola, Deborah; Majsterek, Ireneusz

    2009-01-01

    Tyrosine kinases (TKs) are attractive targets for cancer therapy, as quite often their abnormal signaling has been linked with tumor development and growth. Constitutive activated TKs stimulate multiple signaling pathways responsible for DNA repair, apoptosis, and cell proliferation. During the last few years, thorough analysis of the mechanism underlying tyrosine kinase's activity led to novel cancer therapy using TKs blockers. These drugs are remarkably effective in the treatment of various human tumors including head and neck, gastric, prostate and breast cancer and leukemias. The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia. The introduction of STI571 for the treatment of leukemia in clinical oncology has had a dramatic impact on how this disease is currently managed. Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase. The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava). Herein, we discuss the chemistry, biological activity and clinical potential of new drugs with tyrosine kinase blockers for cancer treatment.

  20. Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

    Institute of Scientific and Technical Information of China (English)

    Davide Ippolito; Davide Fior; Chiara Trattenero; Elena De Ponti; Silvia Drago; Luca Guerra; Cammillo Talei Franzesi; Sandro Sironi

    2015-01-01

    AIM:To assess the clinical diagnostic value of functional imaging,combining quantitative parameters of apparent diffusion coefficient(ADC) and standardized uptake value(SUV)max,before and after chemo-radiation therapy,in prediction of tumor response of patients with rectal cancer,related to tumor regression grade at histology.METHODS:A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study.All patients underwent a whole body 18FDG positron emission tomography(PET)/computed tomography(CT) scan and a pelvic magnetic resonance(MR)examination including diffusion weighted(DW) imaging for staging(PET1,RM1) and after completion(6.6 wk)of neoadjuvant treatment(PET2,RM2).Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings.The MR scanning,performed on 1.5 T magnet(Philips,Achieva),included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm2/s.On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2.The percentage decrease of SUVmax(△SUV) and ADC(△ADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade(Mandard’s criteria;TRG1 = complete regression,TRG5 = no regression).RESULTS:After completion of therapy,all the patients were submitted to surgery.According to the Mandard’s criteria,22 tumors showed complete(TRG1) or subtotal regression(TRG2) and were classified as responders;9tumors were classified as non responders(TRG3,4 and5).Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2(P < 0.001),whereas the mean ADC values was lower in RM1 than RM2(P < 0.001),with a △SUV and △ADC respectively of 60.2%and 66.8%.The best predictors for TRG response were SUV2(threshold of4.4) and ADC2(1.29

  1. Identification of pre- and post-treatment markers, clinical, and laboratory parameters associated with outcome in renal cancer patients treated with MVA-5T4

    Directory of Open Access Journals (Sweden)

    Robert eAmato

    2013-07-01

    Full Text Available The recent approvals of immunotherapeutic agents (Sipuleucel-T and Ipilimumab for the treatment of different solid tumors gave a boost to the growing cancer immunotherapy field, even though few immunotherapy studies have demonstrated convincingly that there is a direct link between the predicted mode of action of an immunological compound and therapeutic benefit. MVA-5T4 (Trovax® is a novel vaccine combining the tumor-associated antigen 5T4 to an engineered vector-modified vaccinia Ankara (MVA. MVA helps to express the oncofetal 5T4 antigen and subsequently trigger a tumor-directed immune reaction. The safety and clinical benefit reported in multiple phase I and II clinical trials using MVA-5T4 were encouraging; immune responses were induced in almost all treated patients, and associations between 5T4-specific cellular or humoral responses and clinical benefit were reported in most of the nine phase II trials. In particular, clinical studies conducted in renal cell carcinoma (RCC patients have demonstrated an association between 5T4-specific (but not MVA antibody responses and enhanced survival. This review describes the clinical studies using MVA-5T4 conducted in RCC that convincingly demonstrated that an antigen-specific immune response induced by vaccination is associated with enhanced patient survival and is not simply a function of the general health of patients. We will also provide our expert opinions on possible future better-designed clinical trials based on relevant biomarkers. In addition, various combinations of MVA-5T4 and different and newer immunomodulator agents with promising clinical benefit will be discussed.

  2. Multiple-factor analysis of the first radioactive iodine therapy in post-operative patients with differentiated thyroid cancer for achieving a disease-free status

    Science.gov (United States)

    Liu, Na; Meng, Zhaowei; Jia, Qiang; Tan, Jian; Zhang, Guizhi; Zheng, Wei; Wang, Renfei; Li, Xue; Hu, Tianpeng; Upadhyaya, Arun; Zhou, Pingping; Wang, Sen

    2016-01-01

    131I treatment is an important management method for patients with differentiated thyroid cancer (DTC). Unsuccessful 131I ablation drastically affects the prognosis of the patients. This study aimed to analyze potential predictive factors influencing the achievement of a disease-free status following the first 131I therapy. This retrospective review included 315 DTC patients, and multiple factors were analyzed. Tumor size, pathological tumor stage, lymph node (LN) metastasis, distant metastasis, American Thyroid Association recommended risks, pre-ablation thyroglobulin (Tg), and thyroid stimulating hormone (TSH) displayed significant differences between unsuccessful and successful group. Cutoff values of Tg and TSH to predict a successful outcome were 3.525 ng/mL and 99.700 uIU/ml by receiver operating characteristic curves analysis. Binary logistic regression analysis showed that tumor stage T3 or T4, LN metastasis to N1b station, intermediate and high risks, pre-ablation Tg ≥ 3.525 ng/ml and TSH <99.700 μIU/mL were significantly associated with unsuccessful outcomes. Logistic regression equation for achieving a disease-free status could be rendered as: y (successful treatment) = −0.270–0.503 X1 (LN metastasis) −0.236 X2 (Tg) + 0.015 X3 (TSH). This study demonstrated LN metastasis, pre-ablation Tg and TSH were the most powerful predictors for achieving a disease-free status by the first 131I therapy. PMID:27721492

  3. POST TRAUMATIC GROWTH PADA PENDERITA KANKER PAYUDARA

    Directory of Open Access Journals (Sweden)

    Erlina Listiyanti Widuri

    2012-03-01

    Full Text Available One of the deadly diseases for women is breast cancer. The wisdomdefined in this study was post traumatic growth. Post traumatic growth is apositive changes experience arising from the struggle of the great crises oflife. The purpose of this study was to determine the growth dynamics ofpost traumatic or post-traumatic growth toward positive life changes andwant to understand further the factors that influence the formation of posttraumatic growth in patients with breast cancer. The method used is basedon qualitative research using phenomenology method. The analysis showedthere were two factors that affecting the aspects of post traumatic growthin patients with breast cancer. External factors are the children andgrandchildren as life expectation and as encouragement or motivationsupport of both parents to perform the treatment, so it eventually leads tothe strengthening of internal factors. Internal factors include the factor offaith (spirituality, a strong desire to recover factors (optimism, resiliencefactors, and reframing factors. There are 4 (four post traumatic growtharising from the struggle with breast cancer in the face of illness: an increasein spirituality, positive improvement in life, and the higher prosocial andbetter social relations.

  4. SU-E-T-79: A Study of the Effect of Clinical Tumor Volume Displacement On the Dosage of Post Modified Radical Mastectomy Intensity-Modulated Radiation Therapy Plans for Left-Sided Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W; Ma, C; Li, D; Wu, F [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China)

    2015-06-15

    Purpose: To explore the effect of clinical tumor volume (CTV) displacement on the dosage of intensity-modulated radiation therapy (IMRT) plans for left-sided breast cancer after modified radical mastectomy. Methods: We created 2 sets of IMRT plans based on PTV0.5 and PTV0.7 (with CTV displacement of 0.5cm and 0.7cm respectively) for each of the ten consecutive left-sided breast cancer patients after modified radical mastectomy, and compared the difference in PTV coverage and organ at risk (OAR) sparing between the two groups. And then, we compared the difference in PTV coverage in IMRT plans based on PTV0.5 between the group with properly estimated CTV displacement (presuming the actual CTV displacement was 0.5cm) and the one with underestimated CTV displacement (presuming the actual CTV displacement was 0.7cm). The difference in results between the corresponding two groups was compared using paired-sample t-test. P values less than 0.05 were considered statistically significant. Results: IMRT plans derived from PTV0.5 had more homogenous PTV coverage, and less heart, left lung, right breast, right lung, left humeral head and B-P radiation exposure, as well as less total Mu as compared with the ones stemmed from PTV0.7 (all p<0.05). IMRT plans with appropriate estimation of CTV displacement had better PTV coverage compared with the ones with underestimated CTV displacement (all p<0.01). Conclusion: The IMRT plans with smaller CTV displacement in post modified radical mastectomy radiotherapy for left-sided breast cancer has dosimetrical advantages over the ones with larger CTV displacement. Underestimation of CTV displacement can lead to significant reduction of PTV coverage. Individually quantifying and minimizing CTV displacement can significantly improve PTV coverage and OAR (including heart and left lung) sparing. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)

  5. 不同序贯的吉非替尼与化疗药物联合对人肝癌细胞Bel-7402增殖的抑制作用%Sequence-Dependent Antiproliferative Effects of Gefitinib and Cytotoxic Drugs on Bel- 7402 Cells

    Institute of Scientific and Technical Information of China (English)

    魏超; 周乃珍; 郭慧; 朱联九; 张盛周

    2011-01-01

    The inhibitory effects of gefitinib combining with different concentrations of adriamycin, fluorouracil, cisplatin and paclitaxel in different sequences on the proliferation of Bel - 7402 cells were evaluated by MTT assay. The results showed that the inhibitory effect of cytotoxic drug combining with gefitinib was better than that of cytotoxic drug treatment alone, the IC50 decreased significantly. The antiproliferative effects of drug combination were affected by different drug sequences, gefitinib used after cytotoxic drugs created better curative effects than that before cytotoxic drugs. These results provided helpful information for hepatocellular carcinoma clinical therapy, they could conduce to less doses and toxic effects in clinical application.%应用MTT法检测了靶向性药物吉非替尼(gefitinib)分别与阿霉素(ADM)、氟尿嘧啶(5-FU)、顺铂(DDP)和紫杉醇(PTX)等4种化疗药物按照不同给药序贯联合作用对肝癌细胞Bel-7402增殖的影响.结果表明,吉非替尼与4种化疗药物联用对Bel-7402细胞增殖的抑制作用效果均要好于单药治疗,其对细胞的IC50较单独用药时明显较低.联合用药效果受到给药序贯的影响,用靶向性药物前先用化疗药物的效果要好于先用靶向性药物后用化疗药物.研究结果可供肝癌临床治疗参考,有助于临床降低用药剂量,减轻药物毒副作用.

  6. 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

    OBJECTIVE: To investigate the effect of the epidermal growth factor receptor (EGFR) on the induction of apoptosis by the chemotherapeutic agent etoposide (VP16), and to examine the effect of combining VP16 with gefitinib to see if the cell-survival mechanism can be prevented. MATERIALS AND METHODS......: 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...

  7. Medical treatment of advanced non-small cell lung cancer: progress in 2014

    Directory of Open Access Journals (Sweden)

    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

  8. Plasma fatty acid ratios affect blood gene expression profiles--a cross-sectional study of the Norwegian Women and Cancer Post-Genome Cohort.

    Science.gov (United States)

    Olsen, Karina Standahl; Fenton, Christopher; Frøyland, Livar; Waaseth, Marit; Paulssen, Ruth H; Lund, Eiliv

    2013-01-01

    High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the

  9. Plasma fatty acid ratios affect blood gene expression profiles--a cross-sectional study of the Norwegian Women and Cancer Post-Genome Cohort.

    Directory of Open Access Journals (Sweden)

    Karina Standahl Olsen

    Full Text Available High blood concentrations of n-6 fatty acids (FAs relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3 in a cross-section of middle-aged Norwegian women (n = 227. After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3, the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes and the AA/EPA ratio (72 genes. All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may

  10. First-line treatment of EGFR-mutated nonsmall cell lung cancer: critical review on study methodology

    Directory of Open Access Journals (Sweden)

    Martin Sebastian

    2014-03-01

    Full Text Available Recent advances in understanding the mechanisms of nonsmall cell lung cancer (NSCLC has led to the development of targeted treatments, including the reversible epidermal growth factor receptor (EGFR tyrosine kinase inhibitors gefitinib and erlotinib, and the irreversible ErbB family blocker afatinib. Several important activating EGFR mutations have now been identified, which correlate strongly with response to treatment with these agents. Multiple randomised controlled trials have confirmed the association between the presence of activating EGFR mutations and objective response to gefitinib, erlotinib and afatinib, thus demonstrating their superiority over platinum-based chemotherapy as first-line treatment for NSCLC patients with EGFR mutation-positive tumours, and resulting in approval of these agents for use in this setting. It can be tempting to compare outcome data across multiple clinical trials and agents; however, substantial differences in methodology between studies, including investigator versus independent assessment and differences in patient eligibility, makes such comparisons fraught with difficulty. This critical review provides an overview of the evolution of the methodology used in eight phase III trials investigating first-line targeted treatment of NSCLC, identifies key differences in methodology and reporting, and critically assesses how these differences should be taken into account when interpreting the findings from such trials.

  11. Stressors in Breast Cancer Post-Treatment: a Qualitative Approach Factores estresantes del post-tratamiento del cáncer de mama: un enfoque cualitativo Estressores pós-tratamento do câncer de mama: um enfoque qualitativo

    Directory of Open Access Journals (Sweden)

    Gisele da Silva

    2010-08-01

    Full Text Available With the increasing effectiveness of breast cancer treatment, the scientific interest in investigating the quality of life of survivors has increased. However, research addressing the post-treatment period is still scarce. The aim of this study was to identify the stressors present in the lives of women in the one to five years post-diagnosis period. The sample was composed of 16 women assisted at a specialized mastectomy rehabilitation service. Data were collected through semi-structured interviews and analyzed using content analysis. The results indicate conflicts with self-image and alteration in the feeling of autonomy, fear in relation to the evolution of the condition, feelings of guilt about the disorder generated in the family, experience of disturbing social situations and a desire to return to their professional occupation. These results reveal the existence of stressors in this phase and the importance of support offered by psychosocial rehabilitation services for this population.Con la creciente resolutividad del tratamiento del cáncer de mama, ha aumentado el interés científico por la investigación de la calidad de vida de las sobrevivientes. Sin embargo, todavía son escasas las investigaciones que abordan el período post-tratamiento. Este estudio tuvo por objetivo identificar los factores estresantes presentes en la vida de mujeres en el período de uno a cinco años post-diagnóstico. Fueron investigadas 16 mujeres atendidas en un servicio especializado en rehabilitación de mastectomizadas. Los datos fueron recolectados mediante entrevista semiestructurada y analizados por medio del análisis de contenido. Los resultados indicaron conflictos con la autoimagen, alteración en la sensación de autosuficiencia, miedo en relación a la evolución del cuadro, sentimiento de culpa por el trastorno generado en la familia, vivencia de situaciones sociales perturbadoras y, deseo de retornar a la ocupación profesional. Esos

  12. Trastuzumab Sensitizes Ovarian Cancer Cells to EGFR-targeted Therapeutics

    Directory of Open Access Journals (Sweden)

    Wilken Jason A

    2010-03-01

    Full Text Available Abstract Background Early studies have demonstrated comparable levels of HER2/ErbB2 expression in both breast and ovarian cancer. Trastuzumab (Herceptin, a therapeutic monoclonal antibody directed against HER2, is FDA-approved for the treatment of both early and late stage breast cancer. However, clinical studies of trastuzumab in epithelial ovarian cancer (EOC patients have not met the same level of success. Surprisingly, however, no reports have examined either the basis for primary trastuzumab resistance in ovarian cancer or potential ways of salvaging trastuzumab as a potential ovarian cancer therapeutic. Methods An in vitro model of primary trastuzumab-resistant ovarian cancer was created by long-term culture of HER2-positive ovarian carcinoma-derived cell lines with trastuzumab. Trastuzumab treated vs. untreated parental cells were compared for HER receptor expression, trastuzumab sensitivity, and sensitivity to other HER-targeted therapeutics. Results In contrast to widely held assumptions, here we show that ovarian cancer cells that are not growth inhibited by trastuzumab are still responsive to trastuzumab. Specifically, we show that responsiveness to alternative HER-targeted inhibitors, such as gefitinib and cetuximab, is dramatically potentiated by long-term trastuzumab treatment of ovarian cancer cells. HER2-positive ovarian carcinoma-derived cells are, therefore, not "unresponsive" to trastuzumab as previously assumed, even when they not growth inhibited by this drug. Conclusions Given the recent success of EGFR-targeted therapeutics for the treatment of other solid tumors, and the well-established safety profile of trastuzumab, results presented here provide a rationale for re-evaluation of trastuzumab as an experimental ovarian cancer therapeutic, either in concert with, or perhaps as a "primer" for EGFR-targeted therapeutics.

  13. Nuclear EGFR as a molecular target in cancer.

    Science.gov (United States)

    Brand, Toni M; Iida, Mari; Luthar, Neha; Starr, Megan M; Huppert, Evan J; Wheeler, Deric L

    2013-09-01

    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell's nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future.

  14. Metastatic gastric cancer – focus on targeted therapies

    Directory of Open Access Journals (Sweden)

    Meza-Junco J

    2012-06-01

    Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

  15. Study Points to Genetic Subtypes of Esophageal Cancer

    Science.gov (United States)

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

  16. Dosimetric comparison of two arcs VMAT plan and IMRT plan for breast cancer post-mastectomy%乳腺癌根治术后双弧VMAT与IMRT计划的剂量学比较

    Institute of Scientific and Technical Information of China (English)

    王佳浩; 李夏东; 邓清华; 吴稚冰; 夏冰; 赖建军; 唐荣军

    2014-01-01

    Objective To analyze the biophysical dosimetric characteristics and clinical application ability of VMAT technology for breast cancer post-mastectomy.Methods 28 patients with breast cancer (10 at left side and the other at right side) were planned in different ways respectively.One was two 90 degree arc VMAT plan and the other were 5 beam IMRT plan.The dosimetric parameters of two different plans including tumor control probability (TCP),conformity index(CI),homogeneity index (HI),V95and V110 in target,normal tissue complication probability (NTCP),V5,V20,V30 for ipsilateral lung,NCTP,D V25 for heart,D for the contralateral breast in OARs,MU and times were compared.Results The average tumor control probability (TCP) in VMAT and IMRT group was(96 ±2)% and (90 ±2)% (t =-6.28,P < 0.01),respectively.The PTV dose average homogeneity index (HI) of VMAT plans was better than that of IMRT plan (0.15 ±0.04 vs 0.22 ±0.02,t =13.29,P <0.01).For cancer position in left side,the mean dose of heart was decreased by 433.24 cGy in the VMAT plan.The NTCP of the hearts in VMAT plans had statistically significant difference compared with IMRT plans [(1.00±0.12)% vs (1.70±0.13)%,t =2.14,P <0.05].For plans of right breast cancer,the average mean dose of hearts in two control group was (3.27 ± 0.26) Gy and (6.00 ± 0.47) Gy (t =9.21,P<0.01).The total monitor unit (MU) was 530.7 in the VMAT arm and 693.9 in the IMRT arm (t =9.58,P <0.01).The treatment time was shorter in VMAT arm (t =8.40,P <0.05).Conclusions VMAT plans have better clinical value and more superior biophysical dosimetric characteristics for breast cancer post-mastectomy.%目的 比较乳腺癌根治术后双弧的容积旋转调强放射治疗(VMAT)与5野的静态调强放射治疗(IMRT)2种计划之间的剂量学差异,评估VMAT技术在乳腺癌根治术后的剂量学特点与应用能力.方法 选取28例乳腺癌根治术后患者(左侧10例,右侧18例),分别制定双90

  17. Impact of Cisplatin and Gefitinib on the proliferation inhibition of nasopharyngeal carcinoma cell lines and their mechanism%顺铂联合吉非替尼对鼻咽癌细胞生长抑制及其机制的探讨

    Institute of Scientific and Technical Information of China (English)

    陈楠; 张红雨; 彭培建; 孟晓军

    2011-01-01

    OBJECTIVE: To investigate that whether Cisplatin can affect the efficacy of Gefitinib through changes in protein expression levels of EGFR and AKT phosphorylation in nasopharyngeal carcinoma cells, and find the marker which can predict the effects of twodrug combination.METHODS: The cell proliferation inhibition rates of single agent of Cisplatin or Gefitinib and two drug combination in three soguehces were detected by MTT assay in CNE1, CNE2 and SUNE1 cell lines.The protein expression levels of EGFR, phosphoEGFR, AKT and phospho-AKT were detected by Western Blot analysis when CNE1 and CNE2 cell lines were exposed to Cisplatin or Gefitinib in different concentrations.RESULTS: In three cell lines, cell proliferation inhibition effect of Cisplatin or Gefitinib was time- and dose-dependent in a certain range of concentrations.With the increasing concentration of Gefitinib exposure, phospho-EGFR or phosphoAKT were down-regulated in CNE1 and CNE2 cell lines.With the increasing concentration of Cisplatin exposure, phospho-EGFR or phospho-AKT were down-regulated in CNE1cell in which antagonistic interaction between Cisplatin and Gefitinib were observed.In addition,the treatment of Cisplatin followed by Gefitinib showed greater antagonistic interaction than that of Gefitinib followed by Cisplatin in CNE1 (P=0.039), With the increasing concentration of Cisplatin exposure, phospho-EGFR or phospho-AKT was up-regulated in CNE2 cell in which synergistic interaction between Cisplatin and Gefitinib were observed.CONCLUSIONS: Cisplatin combined with Gefitinib can result in antagonism and synergism in CNE1 and CNE2 cell line respectively.It may be through changes in protein expression levels of EGFR and AKT phosphorylation that Cisplatin can affect the efficacy of Gefitinib.%目的:探讨在鼻咽癌细胞中顺铂(DDP)是否能通过改变表皮生长因子受体(EGFR)和蛋白激醇B(AKT)的磷酸化蛋白水平以及对吉非替尼疗效的影响,寻找能够预测两者联合

  18. Patient expectancy and post-chemotherapy nausea

    DEFF Research Database (Denmark)

    Colagiuri, Ben; Zachariae, Robert

    2010-01-01

    , specifically controlling for a history of nausea, and involving breast cancer patients, none of the moderators assessed were statistically significant. CONCLUSIONS: These findings suggest that patient expectancies may contribute to post-chemotherapy nausea and that expectancy-based manipulations may provide......BACKGROUND: Post-chemotherapy nausea remains a significant burden to cancer patients. While some studies indicate that expecting nausea is predictive of experiencing nausea, there are a number of conflicting findings. PURPOSE: The purpose of this study was to conduct a meta-analytic review......, there was a robust positive association between expectancy and post-chemotherapy nausea (ESr = 0.18, equivalent to Cohen's d = 0.35), suggesting that patients with stronger expectancies experience more chemotherapy-induced nausea. Although weaker associations were found in studies employing multivariate analysis...

  19. Differential post-surgical metastasis and survival in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null mice with parental and subline variants of human breast cancer: implications for host defense mechanisms regulating metastasis.

    Directory of Open Access Journals (Sweden)

    Chloe C Milsom

    Full Text Available We compare for the first time, the metastatic aggressiveness of the parental MDA-MB-231 breast cancer cell line and two luciferase-tagged in vivo-derived and selected pro-metastatic variants (LM2-4/luc⁺ and 164/8-1B/luc⁺ in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null (NSG mice following orthotopic implantation and primary tumour resection. The variants are known to be more aggressively metastatic in SCID mice, compared to the parental line which has limited spontaneous metastatic competence in these mice. When 2×10⁶ cells were injected into the mammary fat pad, the growth of the resultant primary tumours was identical for the various cell lines in the three strains of mice. However, metastatic spread of all three cell lines, including the MDA-MB-231 parental cell line, was strikingly more aggressive in the highly immunocompromised NSG mice compared to both NOD-SCID and SCID mice, resulting in extensive multi-organ metastases and a significant reduction in overall survival. While these studies were facilitated by monitoring post-surgical spontaneous metastases using whole body bioluminescence imaging, we observed that the luciferase-tagged parental line showed altered growth and diminished metastatic properties compared to its untagged counterpart. Our results are the first to show that host immunity can have a profound impact on the spread of spontaneous visceral metastases and survival following resection of a primary tumour in circumstances where the growth of primary tumours is not similarly affected; as such they highlight the importance of immunity in the metastatic process, and by extension, suggest certain therapeutic strategies that may have a significant impact on reducing metastasis.

  20. SU-E-T-95: An Alternative Option for Reducing Lung Dose for Electron Scar Boost Irradiation in Post-Mastectomy Breast Cancer Patients with a Thin Chest Wall

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y; Kumar, P; Mitchell, M [University of Kansas Medical Center, Kansas City, KS (United States)

    2015-06-15

    Purpose: Breast cancer patients who undergo a mastectomy often require post-mastectomy radiation therapy (PMRT) due to high risk disease characteristics. PMRT usually accompanies scar boost irradiation (10–16Gy in 5–8 fractions) using en face electrons, which often results in increased dose to the underlying lungs, thereby potentially increasing the risk of radiation pneumonitis. Hence, this study evaluated water-equivalent phantoms as energy degraders and as an alternative to a bolus to reduce radiation dose to the underlying lungs for electron scar boost irradiation. Methods: Percent depth dose (PDD) profiles of 6 MeV (the lowest electron energy available in most clinics) were obtained without and with commercial solid water phantoms (1 to 5mm by 1mm increments) placed on top of electron cones. Phantom attenuation was measured by taking a ratio of outputs with to without the phantoms in 10×10cm2 cone size for monitor unit (MU) calculation. In addition, scatter dose to contralateral breast was measured on a human-like phantom using two selected scar (short and long) boost patient setups. Results: The PDD plots showed that the solid water phantoms and the bolus had similar dosimetric effects for the same thickness. Lower skin dose (up to 3%) to ipsilateral breast was observed with a 5mm phantom compared with a 5mm bolus (up to 10%) for all electron cones. Phantom attenuation was increased by 50% with about a 4.5mm phantom. Also, the energy degraders caused scatter dose to contralateral breast by a factor of 3 with a 5mm phantom. Conclusion: Our results demonstrate the feasibility of using water-equivalent phantoms to reduce lung dose using en face electrons in patients with a thin chest wall undergoing PMRT. The disadvantages of this treatment approach (i.e., the increase in MUs and treatment time, and clinically insignificant scatter dose to the contralateral breast given usually 10Gy) are outweighed by its above clinical benefits.

  1. Noninvasive and real-time monitoring of molecular targeting therapy for lymph node and peritoneal metastasis in nude mice bearing xenografts of human colorectal cancer cells tagged with GFP and DsRed

    Science.gov (United States)

    Nakanishi, Hayao; Hara, Masayasu; Ikehara, Yuzuru; Tatematsu, Masae

    2007-02-01

    We have developed an in vivo imaging system consisting of GFP- and DsRed-tagged human colonic cancer cell line, which has peritoneal and lymph node metastatic potential and show high sensitivity to EGFR targeting drugs, and convenient detection devices for GFP and DsRed. The latter includes a small handy fluorescence detection device for external monitoring of the therapeutic effect of the drug and a convenient stereo fluorescent microscope for internal visualization of micrometastases. We applied this imaging system to investigate anti-metastatic effects of EGFR targeting drugs such as gefitinib (Iressa). This system allowed sensitive detection of the development of peritoneal and lymph node metastases from the micrometastasis stage at the cellular level and also permited noninvasive, non-anesthetic monitoring of anti-metastatic effect of the drug in an animal facility without any pretreatment. Significant decreases in the intraabdominal metastatic tumor growth and prevention of inguinal lymph node metastasis by gefitinib treatment could be clearly monitored. These results suggest that convenient, low-cost, true real-time monitoring of therapeutic effect using such a fluorescence-mediated whole body imaging system seems to enhance the speed of preclinical study for novel anti-cancer agents and will allow us to understand the action mechanism of molecular targeting drugs.

  2. 非小细胞肺癌分子靶向治疗中EGFR-TKI的耐药机制研究进展%Research Progress on Resistance Mechanisms of Epidermal Growth Factor Receptor Tvrosine Kinase Inhibitors in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李媛

    2012-01-01

    With a greater understanding of tumor biology, novel molecular-targeted strategies that block cancer progression pathways have been evaluated as a new therapeutic approach for treating non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer in some populations of NSCLC patients. However, the efficacy of EGFR-TKIs is limited by either primary (de novo) or acquired resistance after therapy. This review will focus on recently identified mechanisms of primary and acquired resistance to EGFR TKIs and strategies currently being employed to overcome resistance.%随着分子靶向治疗药物的发展,以吉非替尼( gefitinib,iressa)和厄洛替尼(erlotinib,tarceva)为代表的表皮生长因子受体酪氨酸激酶抑制剂( epidermal growth factor receptor-tyrosine kinases inhibitors,EGFR-TKIs)在治疗非小细胞肺癌中发挥了重要作用.然而在临床前和临床研究中发现许多患者对此药物存在原发性耐药或获得性耐药,使该类药物的使用受到一定限制.本文就近年来对EGFR-TKIs耐药机制的研究进展进行综述.

  3. 阿法替尼联合西妥昔单抗治疗非小细胞肺癌EGFR T790M突变所致的吉非替尼耐药%Overcoming acquired resistance to gef(i)tinib in NSCLC with EGFR T790M mutation using combination of afatinib and cetuximab

    Institute of Scientific and Technical Information of China (English)

    李静; 武新虎; 刘志冰; 王振; 宋勇; 朱锡旭

    2013-01-01

    目的:探讨阿法替尼联合西妥昔单抗对非小细胞肺癌(non-small cell lung cancer,NSCLC)表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M突变所致继发性耐药的作用.方法:培养EGFRT790M突变所致继发性耐药的NSCLC患者的原代细胞,胶原凝胶体包埋药敏技术检测阿法替尼(10 nmol/L)和西妥昔单抗(50 μg/mL)对NSCLC原代细胞的敏感性,WST-1和FCM法观察联合用药对NSCLC原代细胞增殖和凋亡的影响.结果:阿法替尼联合西妥昔单抗对EGFR T790M突变阳性的继发性耐药的NSCLC原代细胞的敏感性高于单药组(P<0.05);阿法替尼联合西妥昔单抗组NSCLC原代细胞存活率低于单药组(P<0.05),而细胞凋亡率高于单药组(P<0.05).结论:阿法替尼联合西妥昔单抗对EGFR T790M突变所致耐药的NSCLC原代细胞有效.%Objective:To investigate the effect of afatinib combined with cetuximab on the acquired resistance in NSCLC (non-small cell lung cancer) with EGFR (epidermal growth factor receptor) T790M mutation.Methods:The sensitivity to afatinib (10 nmol/L) in combination with cetuximab (50 μg/mL) in the primary NSCLC cells with EGFR T790M mutation was investigated by CD-DST (collagen-gel droplet embedded-culture drug sensitivity test).The proliferative and apoptotic rates of primary NSCLC cells after treatment with afatinib in combination with cetuximab were detected by cell proliferation assay (WST-1)and flow cytometry,respectively.Results:The sensitivity to combination of afatinib and cetuximab in the primary NSCLC cells with EGFR T790M mutation was higher than that to afatinib or cetuximab alone (P <0.05).The survival rate of the primary NSCLC cells after treatment with afatinib and cetuximab was lower than that in the cells treated with afatinib or cetuximab alone (P < 0.05),whereas the apoptotic rate was reverse (P < 0.05).Conclusion:Afatinib in combination with cetuximab is effective to reverse resistance to gefitinib in

  4. Identification of drugs that restore primary cilium expression in cancer cells.

    Science.gov (United States)

    Khan, Niamat Ali; Willemarck, Nicolas; Talebi, Ali; Marchand, Arnaud; Binda, Maria Mercedes; Dehairs, Jonas; Rueda-Rincon, Natalia; Daniels, Veerle W; Bagadi, Muralidhararao; Thimiri Govinda Raj, Deepak Balaji; Vanderhoydonc, Frank; Munck, Sebastian; Chaltin, Patrick; Swinnen, Johannes V

    2016-03-01

    The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties.

  5. Application of SWO technique in IMRT plan of post-operative cervical cancer%子野权重优化在宫颈癌术后IMRT计划中的应用研究

    Institute of Scientific and Technical Information of China (English)

    李毅; 陈鑫; 李文荣; 张晓智

    2013-01-01

    目的 探讨子野权重优化(SWO)技术对宫颈癌根治术后调强放疗(IMRT)计划总子野数、总机器跳数(MU)、靶区均匀性指数(HI)、适形度指数(CI)以及靶区和正常组织照射剂量的影响.方法 随机抽样选取10例接受根治术后的Ⅰ~Ⅱ期宫颈癌患者,应用ELEKTA XI0 4.62系统,采用相同的射野方向和优化参数,利用静态调强(Step&Shoot)的传统方法优化,作为S-IMRT计划;同时,应用SWO对IMRT计划做进一步的优化,作为SWO-IMRT计划.比较子野权重优化前后总子野数、总MU数的变化,同时利用剂量体积直方图(DVH)评价靶区均匀性指数(HI)、适形度指数(CI)以及靶区和正常组织照射剂量.结果 与S-IM RT计划比较,SWO-IMRT计划的平均子野数由(96±4)个降至(87±4)个(t=10.049,P<0.05);MU数由(638.79±35.02) cGy增至(672.03±39.07)cGy(t=3.952,P<0.05);计划靶区(PTV)最大剂量(Dmax)和平均剂量(Dmean)降低(t=2.262、2.323,P<0.05);脊髓最大剂量(Dmax)由(3856.00±112.14)cGy降至(3750.00±141.38)cGy(t=3.976,P<0.05);SWO-IMRT计划膀胱V30、V40、V50,直肠V30,左侧股骨头V50的剂量低于S-IMRT计划(t=4.223、5.801、7.534、2.451、2.269、3.976,P<0.05);对于靶区剂量均匀性指数(HI)、适形度指数(CI)、直肠V40、V50,左侧股骨头V30、V40、V50,右侧股骨头V40、V50,差异无统计学意义.结论 SWO技术应用于宫颈癌根治术后IMRT计划中,总子野数减少,总MU数增加,脊髓和膀胱剂量降低.既降低了脊髓和膀胱的不良反应,也为肿瘤剂量的提高提供了可能.SWO技术为临床工作提供了一种可选择的优化工具.%Objective To investigate the impact of segment weight optimization(SWO) technique on the intensity modulated radiation therapy(IMRT) plan for post-operative cervical cancer regarding the number of segments,monitor units (MU),the target homogeneity index (HI),conformal index (CI) and dose distribution of target volume and normal tissues

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

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kayo OSAWA

    2009-08-01

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

  8. 食管癌术后管道护理风险因素分析及防范对策%An analysis of the risk factors in the post-operative nursing care of the esophagus cancer for esophagus as well as precautions and countermeasures

    Institute of Scientific and Technical Information of China (English)

    赵红凤; 陈东桂; 谢秀萍

    2011-01-01

    Objective To summarize the risk factors in the post - operative nursing care of the esophagus cancer for the esophagus as well as the precautions and countermeasures. Methods A retrospective analysis of 35 cases of the post - operative nursing care for the esophagus was carried out. Results It turns out that the factors in the patients themselves, the esophagus and the nursing staff were the main factors which contributed to the risks of post - operative nursing care for the esophagus. Conclusion In conclusion, good management of post- operative patients, esophagus and the staff are key factors to prevent the risks of the esophagus cancer caused by post- operative nursing care for the esophagus and reduce the fatality rates and postoperative complications.%目的 总结食管癌术后管道护理风险因素及防范对策.方法 对35例食管癌术后管道护理进行回顾性总结分析.结果 患者本身因素、管道因素、护理人员因素是导致食管癌术后管道护理风险发生的主要因素.结论 加强术后患者、管道和护理人员管理,能有效预防食管癌术后管道护理风险发生,降低术后并发症和病死率发生.

  9. 影响乳腺癌术后精确放疗的因素分析%Impact of treatment set-up errors on accuracy of post-operation radiotherapy in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    龚建舟; 张萍; 俞晓立; 陈佳艺

    2009-01-01

    背景与目的:乳腺癌精确放疗的实施有赖于定位、计划及治疗实施等多个步骤的协作完成.本研究探讨乳腺癌切线野放射治疗实施过程中摆位误差对精确治疗的影响.方法:共入组50例改良根治术后或保留乳房术后乳腺癌患者,放疗靶区主要为患侧胸壁和(或)乳腺.放射治疗技术以切线野等中心治疗为原则,在此基础上针对不同患者选择采用半野照射或MLC多叶光栅照射技术.患者治疗时仰卧于MED-TEC250型乳腺托架,治疗设备为Eleckta Precise加速器.在患者每次治疗过程中在摆位完毕后,按内切野治疗前-内切野治疗后-外切野治疗后顺序分别记录加速器所显示X、Y、Z读数,X代表左右方向的移动度,Y代表头脚方向的移动度,Z代表腹背方向的移动度.结果:最大的平均位移差值为第1周,在Z轴、Y轴、X轴方向分别为2.55、3.96、0.58 cm.3个方向中,随时间推移Z轴方向移动最大.从其他影响因素考虑,发现上肢活动情况及托架位置对患者治疗的移动变化影响大. 结论:在乳腺癌患者切线野放射治疗中,内切野治疗后患者的移动度较外切野治疗后大;从不同轴向而言,X方向(左右方向)移动明显小于Y方向(头脚方向)和Z方向(腹背方向);从整个疗程而言,前2周中患者的移动度较大,而从第3周起,患者移动度变小并且趋于稳定.%Background and purpose: The precise radiotherapy in patients with breast cancer consists of multiple procedures, such as simulation, treatment planning and delivery. We assessed the impact of treatment set-up errors on accuracy of post-operative radiotherapy (RT) in patients with breast cancer receiving tangential RT. Methods: Between November 2007 and August 2008, a total of 50 patients were enrolled an institutional review board-approved study. All patients received tangential RT for either right or left breast cancer. Read-out numbers of X, Y, Z directions shown on

  10. Study on the relationship of post- traumatic growth with self- care efficacy and psychological resilience in patients with breast cancer%乳腺癌患者自我管理效能感及心理弹性与其创伤后成长的相关性研究

    Institute of Scientific and Technical Information of China (English)

    贾晓琴; 程玲灵; 杨芳; 孙玉倩; 刘钰

    2015-01-01

    目的:探讨乳腺癌患者自我管理效能感及心理弹性与创伤后成长的相关性。方法运用创伤后成长量表(PTGI)、中文版癌症自我管理效能感量表(C- SUPPH)、中文版心理弹性问卷(CD-RISC),对303例乳腺癌患者进行问卷调查。结果乳腺癌患者 PTGI 总分(63.74±13.00)分,处于中等水平,其中人际关系维度得分最高(24.49±5.05)分,精神变化维度得分最低(3.84±1.91)分;相关分析显示,乳腺癌患者创伤后成长与自我管理效能感、心理弹性水平均呈正相关,具有统计学意义, P<0.01或0.05;回归分析显示,自我管理效能感、心理弹性能较好地预测乳腺癌患者创伤后成长,解释率达36.1%。结论乳腺癌患者自我管理效能感、心理弹性与创伤后成长密切相关,临床上应采取针对性措施促进乳腺癌患者的创伤后成长,增进心理健康。%Objective To explore the relationships of post- traumatic growth with self- care efficacy and psychological resilience in patients with breast cancer. Methods Totally 303 patients with breast cancer were investigated with Post- traumatic Growth Inventory (PTGI), Chinese version of Strategies Used by People to Promote Health (C- SUPPH) and Connor- Davidson Resilience Scale (CD- RISC). Results The total score of PTGI was 63.74±13.00 and the status of post- traumatic growth in breast cancer patients was in middle level, with a highest interpersonal score of 24.49±5.05, a lowest mental change score of 3.84± 1.91. Correlation analysis showed that post- traumatic growth was positively correlated with the level of self- care efficacy and psychological resilience (P<0.01 or 0.05). Regression analysis showed that self- care efficacy and psychological resilience in breast cancer patients could effectively predict the post- traumatic growth with an explanation rate of 36.1%. Conclusions Self- care efficacy and psychological resilience in

  11. Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations.

    Science.gov (United States)

    Suzawa, Ken; Toyooka, Shinichi; Sakaguchi, Masakiyo; Morita, Mizuki; Yamamoto, Hiromasa; Tomida, Shuta; Ohtsuka, Tomoaki; Watanabe, Mototsugu; Hashida, Shinsuke; Maki, Yuho; Soh, Junichi; Asano, Hiroaki; Tsukuda, Kazunori; Miyoshi, Shinichiro

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It plays an important role in the pathogenesis of certain human cancers. In non-small-cell lung cancer (NSCLC), HER2 amplification or mutations have been reported. However, little is known about the benefit of HER2-targeted therapy for NSCLCs harboring HER2 alterations. In this study, we investigated the antitumor effect of afatinib, an irreversible epidermal growth factor receptor (EGFR)-HER2 dual inhibitor, in lung cancers harboring HER2 oncogene alterations, including novel HER2 mutations in the transmembrane domain, which we recently identified. Normal bronchial epithelial cells, BEAS-2B, ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, and G660D) showed constitutive autophosphorylation of HER2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to gefitinib. Furthermore, we examined the antitumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alterations and sensitivity to afatinib treatment. In HER2-altered NSCLC cells (H2170, Calu-3, and H1781), afatinib downregulated the phosphorylation of HER2 and EGFR as well as their downstream signaling, and induced an antiproliferative effect through G1 arrest and apoptotic cell death. In contrast, HER2- or EGFR-non-dependent NSCLC cells were insensitive to afatinib. In addition, these effects were confirmed in vivo by using a xenograft mouse model of HER2-altered lung cancer cells. Our results suggest that afatinib is a therapeutic option as a HER2-targeted therapy for NSCLC harboring HER2 amplification or mutations.

  12. 78 FR 27408 - National Cancer Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-05-10

    ... Methods for the Detection of Cancer Recurrence in Post-Therapy Breast Cancer Patients. Date: June 4, 2013... of Federal Domestic Assistance Program Nos. 93.392, Cancer Construction; 93.393, Cancer Cause and... HUMAN SERVICES National Institutes of Health National Cancer Institute; Notice of Closed...

  13. Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

    Science.gov (United States)

    Kurbel, Beatrica; Golem, Ante Zvonimir; Kurbel, Sven

    2015-01-01

    Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

  14. Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown

    Science.gov (United States)

    Srikar, R.; Suresh, Dhananjay; Zambre, Ajit; Taylor, Kristen; Chapman, Sarah; Leevy, Matthew; Upendran, Anandhi; Kannan, Raghuraman

    2016-08-01

    A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation.

  15. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  16. Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses

    Directory of Open Access Journals (Sweden)

    Wang HY

    2016-05-01

    Full Text Available Hsian-Yu Wang,1,2 Min-Kung Hsu,3,4 Kai-Hsuan Wang,1 Ching-Ping Tseng,2,4 Feng-Chi Chen,3,4 John T-A Hsu1,4 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU, Hsinchu, 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 4Department of Biological Science and Technology, National Chiao Tung University (NCTU, Hsinchu, Taiwan, Republic of China Background: Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs, such as gefitinib, erlotinib, and afatinib, have greatly improved treatment efficacy in non-small cell lung cancer (NSCLC patients with drug-sensitive EGFR mutations. However, in some TKI responders, the benefits of such targeted therapies are limited by the rapid development of resistance, and strategies to overcome this resistance are urgently needed. Studies of drug resistance in cancer cells typically involve long term in vitro induction to obtain stably acquired drug-resistant cells followed by elucidation of resistance mechanisms, but the immediate responses of cancer cells upon drug treatment have been ignored. The aim of this study was to investigate the immediate responses of NSCLC cells upon treatment with EGFR TKIs.Results: Both NSCLC cells, ie, PC9 and H1975, showed immediate enhanced adhesion-related responses as an apoptosis-countering mechanism upon first-time TKI treatment. By gene expression and pathway analysis, adhesion-related pathways were enriched in gefitinib-treated PC9 cells. Pathway inhibition by small-hairpin RNAs or small-molecule drugs revealed that within hours of EGFR TKI treatment, NSCLC cells used adhesion-related responses to combat the drugs. Importantly, we show here that the Src family inhibitor, dasatinib, dramatically inhibits

  17. 癌性疲乏干预对提高乳腺癌术后患者生存质量的效果研究%Effects of cancer-related fatigue intervention on improving the quality of life in post-operative patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    陈旭东; 刘宝凤; 贾淑媛

    2012-01-01

    Objective To explore the effects of cancer-related fatigue (CRF) intervention on improving the quality of life in post-operative patients with breast cancer.Methods Seventy post-operative breast cancer patients were equally divided into the interventional group and the control group. Both groups received conventional nursing service,and the former one received additional cancer-related fatigue nursing intervention,including the CRF valuation,evidence-based nursing,emotion and information support,cognitive intervention,self-care mode and personalized care.Then cancer related fatigue and quality of life between both group patients before and after intervention were analyzed by applying simple fatigue rating scale and quality of life questionnaire.Results There was no significant difference between the score of PFS and QOL before the intervention (4.59 ± 1.66 vs 4.61 ± 1.70,P >0.05 ).After intervention,the score of PFS of the interventional group was significantly lower than that in the control group (4.66 ± 1.12 vs 5.52 ± 1.61 ; t =2.928,P <0.05).After intervention,the QOL of the interventional group including general health (60.82 ± 9.12 vs 54.05 ± 6.77 ),body function (66.76 ± 9.82 vs 60.58 ± 11.89 ),role function ( 64.39 ± 12.59 vs 58.24 ±12.09),motion function (65.62 ±8.31 vs 60.13 ±9.56),the cognition function(71.91 ±9.14 vs 65.30 ±11.92) and social function (66.75 ± 12.76 vs 60.82 ± 13.59) were significantly better than that of the control group (P < 0.05 ).Conclusions According to the nursing procedure,cancer-related fatigue intervention including the CRF valuation,analyze the CRF reasons and building up individuation intervention could alleviate CRF and improve the patients' QOL.%目的 探讨癌性疲乏(CRF)护理干预对乳腺癌术后患者生存质量的效果.方法 采用随机数字表法将70例乳腺癌术后患者随机分为干预组35例、对照组35例.对照组接受常规护理,观察组在接受常规护理的基础

  18. Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Keisuke Tabara

    Full Text Available Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs. However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11-18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11-18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11-18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2 or BIBW2992 (pan-TKI of EGFR family proteins. Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance.

  19. [Flexible root posts].

    Science.gov (United States)

    Vadachkoriia, N R; Mandzhavidze, N A; Gumberidze, N Sh

    2009-02-01

    The article discusses the current state of restoration techniques of root canal treatment. Nowadays, technical progress allows manufacturers to develop flexible fiberglass posts, aspiring not only to an excellent aesthetics and mechanical properties (first of all, in comparison with metal and cast posts), but also to maintenance of their radio density and a wide range of forms. Growth of fiberglass posts popularity testifies to their clinical efficiency that also is confirmed by results of long-term researches. Introduction of fiberglass posts in a dental practice has rendered huge influence on restoration techniques of root canal treatment. Convincing factors of fiberglass posts superiority provide restoration the appearance similar with the natural dentition; possess close to dentine elasticity; creation of monolithic structure with hard tooth tissues and composite cement, posts, in case of need, can be easily adjusted on length, adhesive linkage of posts gives them additional stability. Modern researches have confirmed that only elastic, namely carbon fiber and the fiberglass posts made of modern technologies possess similar physical properties, as tooth structure. They can create reliable biomimetic design; solve a complex of aesthetic and functional restoration problems.

  20. Fence Posts and Rails

    Science.gov (United States)

    Turton, Roger

    2016-01-01

    "Mathematical Lens" uses photographs as a springboard for mathematical inquiry and appears in every issue of "Mathematics Teacher." Recently while dismantling an old wooden post-and-rail fence, Roger Turton noticed something very interesting when he piled up the posts and rails together in the shape of a prism. The total number…

  1. Post-Session Authentication

    DEFF Research Database (Denmark)

    Ahmed, Naveed; Jensen, Christian D.

    2012-01-01

    . In this paper, we consider the case of post-session authentication, where parties authenticate each other at the end of their interactive session. This use of authentication is different from session-less authentication (e.g., in RFID) and pre-session authentication (e.g., for access control.) Post...

  2. Post-Concussion Syndrome

    Science.gov (United States)

    ... if you're having problems with memory or problem-solving. There is no specific treatment for post-concussion ... for post-concussion syndrome if you have cognitive problems, as most of them ... or other techniques to work around memory deficits and attention skills. ...

  3. Post-Polio Syndrome

    Science.gov (United States)

    ... or fatigue, this may overwork already stressed-out motor neurons and increase your risk of post-polio syndrome. Generally, post-polio syndrome is rarely life-threatening, but severe muscle weakness can lead to complications: Falls. Weakness in your leg muscles makes it ...

  4. Commitments by hostage posting

    NARCIS (Netherlands)

    Raub, W.; Baurmann, M.; Lahno, B.

    2009-01-01

    We survey research on incurring commitments by voluntary hostage posting as a mechanism of cooperation. The Trust Game is employed as a paradigmatic example of cooperation problems. We sketch a very simple game-theoretic model that shows how voluntary hostage posting can bind the trustee and thus in

  5. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA.

    Science.gov (United States)

    Murtaza, Muhammed; Dawson, Sarah-Jane; Tsui, Dana W Y; Gale, Davina; Forshew, Tim; Piskorz, Anna M; Parkinson, Christine; Chin, Suet-Feung; Kingsbury, Zoya; Wong, Alvin S C; Marass, Francesco; Humphray, Sean; Hadfield, James; Bentley, David; Chin, Tan Min; Brenton, James D; Caldas, Carlos; Rosenfeld, Nitzan

    2013-05-02

    Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection. Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a non-invasive liquid biopsy. Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over 1-2 years. For each case, exome sequencing was performed on 2-5 plasma samples (19 in total) spanning multiple courses of treatment, at selected time points when the allele fraction of tumour mutations in plasma was high, allowing improved sensitivity. For two cases, synchronous biopsies were also analysed, confirming genome-wide representation of the tumour genome in plasma. Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance. These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel; a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin; a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab, and following subsequent treatment with lapatinib, a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib. These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify

  6. Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

    Energy Technology Data Exchange (ETDEWEB)

    Jorge, S.E.D.C.; Kobayashi, S.S.; Costa, D.B. [Harvard Medical School, Beth Israel Deaconess Medical Center, Department of Medicine, Division of Hematology/Oncology, Boston, MA (United States)

    2014-09-05

    Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

  7. Epidermal growth factor receptor (EGFR mutations in lung cancer: preclinical and clinical data

    Directory of Open Access Journals (Sweden)

    S.E.D.C. Jorge

    2014-11-01

    Full Text Available Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC, the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs. Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686 and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

  8. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Antonelli, Giovanna; Libra, Massimo; Panebianco, Vincenzo; Russo, Alessia Erika; Vitale, Felice Vito; Colina, Paolo; D'Angelo, Alessandro; Rossello, Rosalba; Ferraù, Francesco

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

  9. Targeting the MET gene for the treatment of non-small-cell lung cancer.

    Science.gov (United States)

    Gelsomino, F; Facchinetti, F; Haspinger, E R; Garassino, M C; Trusolino, L; De Braud, F; Tiseo, M

    2014-02-01

    Recently, a better understanding of the specific mechanisms of oncogene addiction has led to the development of antitumor strategies aimed at blocking these abnormalities in different malignancies, including lung cancer. These abnormalities trigger constitutive activation of tyrosine kinase receptors (RTKs) involved in fundamental cell mechanisms such as proliferation, survival, differentiation and migration, and consequently the aberrant signaling of RTKs leads to cancer growth and survival. The inhibition of aberrant RTKs and downstream signaling pathways has opened the door to the targeted therapy era. In non-small-cell lung cancer (NSCLC), molecular research has allowed the discrimination of different aberrant RTKs in lung cancer tumorigenesis and progression, and thus the identification of several targetable oncogenic drivers. Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target. Moreover, according to current knowledge, MET could be considered both as a secondary oncogenic mechanism and as a prognostic factor. Several therapeutic strategies for inhibiting activated hepatocyte growth factor receptor (HGFR) and the subsequent downstream signaling transduction have been improved in order to block tumor growth. This review will focus on the MET pathway and its role in resistance to EGFR TK (tyrosine kinase) inhibitors, the different strategies of its inhibition, and the potential approaches to overcoming acquired resistance.

  10. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  11. [Let Us to Know the Post-Marketing Clinical Studies and Critical Situation of Study Groups -- Now We Should Talk about How to Achieve the Safe and Most Effective Treatment for Cancer Patients].

    Science.gov (United States)

    Hamamoto, Maki

    2016-04-01

    Not to leave something to be regretted in the life of patients and their family, it is important to find the best way during and after treatment for cancer. We, cancer survivors association, propose a corporated actions among patients, administration, medical stuffs, and enterprises to solve the problems of clinical studies. And we express our opinion on the present problems and to do for patients and citizens.

  12. Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

    Directory of Open Access Journals (Sweden)

    Collantes Maria

    2010-05-01

    Full Text Available Abstract Background There is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs leads to tumor growth, progression, invasion and metastasis. Erlotinib and gefitinib, two EGFR-targeted agents, have been shown to be relevant drugs for lung cancer treatment. Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the activity of lapatinib against non-small cell lung cancer (NSCLC. Methods We selected the lung cancer cell line A549, which harbors genomic amplification of EGFR and HER-2. Proliferation, cell cycle analysis, clonogenic assays, and signaling cascade analyses (by western blot were performed in vitro. In vivo experiments with A549 cells xenotransplanted into nude mice treated with lapatinib (with or without radiotherapy were also carried out. Results Lapatinib dramatically reduced cell proliferation (P P P in vitro. Furthermore, lapatinib induced G1 cell cycle arrest (P P In vivo experiments revealed that A549 tumor-bearing mice treated with lapatinib had significantly less active tumors (as assessed by PET analysis (P P Conclusion Overall, these data suggest that lapatinib may be a clinically useful agent for the treatment of lung cancer.

  13. Post-Approval Studies

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a...

  14. Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines.

    Science.gov (United States)

    Yagui-Beltrán, Adam; Coussens, Lisa M; Jablons, David M

    2009-01-01

    Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

  15. Afatinib-refractory brain metastases from EGFR-mutant non-small-cell lung cancer successfully controlled with erlotinib: a case report.

    Science.gov (United States)

    Nonagase, Yoshikane; Okamoto, Kunio; Iwasa, Tsutomu; Yoshida, Takeshi; Tanaka, Kaoru; Takeda, Masayuki; Kaneda, Hiroyasu; Shimizu, Toshio; Tsurutani, Junji; Nakagawa, Kazuhiko

    2016-03-01

    Both afatinib and erlotinib are tyrosine kinase inhibitors that inhibit aberrant epidermal growth factor receptor (EGFR) signals in non-small-cell lung cancer (NSCLC). Afatinib is an irreversible inhibitor directed against EGFR, ErbB-2, and ErbB-4, whereas erlotinib is a reversible inhibitor directed against EGFR only. Although afatinib has been shown to be effective in the treatment for erlotinib-refractory and/or gefitinib-refractory central nervous system metastases from NSCLC, little is known about the efficacy of erlotinib for afatinib-refractory central nervous system metastases. In the present report we describe a case of EGFR mutation-positive NSCLC in which brain metastases developed during first-line afatinib treatment. Whole-brain radiation therapy and substitution of erlotinib for afatinib led to successful shrinkage of the brain metastases. Our report highlights the potential benefit of erlotinib for the management of brain metastases refractory over afatinib in patients with NSCLC.

  16. The importance of molecular profiling in predicting response to epidermal growth factor receptor family inhibitors in non-small-cell lung cancer: focus on clinical trial results.

    Science.gov (United States)

    Tsao, Anne S; Papadimitrakopoulou, Vassiliki

    2013-07-01

    In recent years, the epidermal growth factor receptor (EGFR) family has become a key focus of non-small-cell lung cancer biology and targeted therapies, such as the reversible EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Initially, response to these agents was associated with certain demographic and clinical characteristics; subsequently, it was discovered that these subgroups were more likely to harbor specific mutations in the EGFR gene that enhanced tumor response. However, the presence of these mutations does not equate to therapeutic success. Other aspects of EGFR family signaling, including other types of EGFR mutations, EGFR protein expression, EGFR gene amplification, mediators of downstream signaling, and other receptors with similar downstream pathways may all play a role in response or resistance to treatment. The identification of these and other molecular determinants is driving the development of novel therapies designed to achieve improved clinical outcomes in patients.

  17. Drug Reduces Cancer Treatment-Related Joint Pain

    Science.gov (United States)

    A Cancer Currents blog post about a clinical trial demonstrating that duloxetine (Cymbalta®) may reduce joint pain caused by aromatase inhibitors in women being treated for early-stage breast cancer.

  18. Sono, qualidade de vida e depressão em mulheres no pós-tratamento de câncer de mama Sleep, quality of life and depression in women in breast cancer post-treatment

    Directory of Open Access Journals (Sweden)

    Renatha El Rafihi-Ferreira

    2012-01-01

    Full Text Available 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 queixas de nictúria, calor e despertares noturnos. O grupo clínico com má qualidade do sono apresentou comprometimento na qualidade de vida e mais sintomas de depressão. Em geral, a qualidade de sono em mulheres com câncer de mama pode predizer a qualidade de vida e o bem estar psicológico.This study investigated the sleep quality of women with breast cancer and their relationship with quality of life and depression. Fifty women with breast cancer (clinical group and a control group of other 50 women without the disease answered a clinical-demographic questionnaire and the Pittsburgh Sleep Quality Index. The clinical group also completed the Quality of Life Cancer-Survivor and the Brief Zung Self-Rating Depression Scale questionnaires. It was found that women with breast cancer had significantly more complaints of nocturia, heat and nighttime awakenings. The clinical group with poor quality of sleep reported impaired quality of life and more symptoms of depression. In general terms, sleep quality in women with breast cancer can predict their quality of life and psychological well-being.

  19. Prevalence, socio-demographic and clinical predictors of post-diagnostic utilisation of different types of complementary and alternative medicine (CAM) in a nationwide cohort of Danish women treated for primary breast cancer

    DEFF Research Database (Denmark)

    Pedersen, Christina Gundgaard; Christensen, Søren; Jensen, Anders Bonde;

    2009-01-01

    This study investigated the prevalence and predictors of use of complementary and alternative medicine (CAM) in a nationwide inception cohort of Danish women treated for early-stage breast cancer as well as differences in user patterns for individual types of CAM.......This study investigated the prevalence and predictors of use of complementary and alternative medicine (CAM) in a nationwide inception cohort of Danish women treated for early-stage breast cancer as well as differences in user patterns for individual types of CAM....

  20. Computer Security: posting and mis-posting

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2015-01-01

    This is what can happen at CERN if you don't lock your computer screen...   “Hi, I am looking for a partner either male or female to attend salsa lessons. I have a great body and enjoy rubbing it against other people on the dance floor. I would consider dinner after with the right person. If you think you can keep up with me and enjoy getting sweaty send me a reply. Stay sexy…” This is the original text of a recent posting on the CERN Market webpage. Some people might find this appealing, some people think this is funny. Personally, I couldn’t care less. But professionally, we had to follow up as this text can be perceived as inappropriate and, thus, in violation of the Terms of Usage of the CERN Market as well as the CERN Computing Rules and its annex on private usage of the CERN computing facilities. We remind you that the CERN Market is a public website that can be used by people within but also outside CERN. All posts are visible world...

  1. Esthetic Intracanal Posts

    Science.gov (United States)

    Parčina, Ivana; Amižić

    2016-01-01

    The primary function of an endodontic post is to provide retention for the