WorldWideScience

Sample records for cancer chemotherapy resistance

  1. Chemotherapy options in castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Benjamin A Teply

    2016-01-01

    Full Text Available Introduction: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. Methods: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents. We also reviewed emerging data on biomarkers of response to chemotherapy for CRPC. Results: Taxanes, especially docetaxel and cabazitaxel, have first- and second-line indications for CRPC, respectively, with both providing a survival benefit. Multiple attempts to improve on the single agent efficacy of docetaxel with combination therapy have not generally been successful although platinum combinations are used for resistant phenotypes. Reductions in prostate-specific antigen by ≥30% and reductions in circulating tumor cells (CTCs to ≤ 5 are associated with improved survival on chemotherapy. Chemotherapy may continue to be effective therapy for patients with biomarkers that are associated with resistance to androgen-directed therapies (androgen receptor splice variant 7 positivity in CTCs or high CTC heterogeneity. Conclusions: Chemotherapy remains an essential component of CRPC therapy, and biomarkers are being identified to define clinical scenarios where chemotherapy may be the optimal therapy choice.

  2. Cancer Chemotherapy

    Science.gov (United States)

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

  3. Advances in Hypoxia Microenvironment and Chemotherapy-resistant 
of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yang GUO

    2014-03-01

    Full Text Available Lung cancer is one of the malignant tumors with highest incidence recently in our country. Tumor hypoxia phenomenon was first discovered in lung cancer. It plays important roles in tumor cell drug-resistance, apoptosis, invasion and metastasis, angiogenesis. Chemotherapy-resistant is one of the core reasons of treatment failure and disease progress, and many works on the study of chemotherapy-resistant have been done. This article reviewed the research progress of those mechanisms by which lung cancer hypoxia microenvironment could induce chemotherapy-resistance.

  4. SIRT1/PGC1α-Dependent Increase in Oxidative Phosphorylation Supports Chemotherapy Resistance of Colon Cancer

    NARCIS (Netherlands)

    Vellinga, Thomas T.; Borovski, Tijana; de Boer, Vincent C. J.; Fatrai, Szabolcs; van Schelven, Susanne; Trumpi, Kari; Verheem, Andre; Snoeren, Nikol; Emmink, Benjamin L.; Koster, Jan; Rinkes, Inne H. M. Borel; Kranenburg, Onno

    2015-01-01

    Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms. We studied gene expression differences between groups of liver metastases

  5. Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance.

    Science.gov (United States)

    Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K

    2017-03-14

    This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.

  6. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early......-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression...

  7. Mechanisms of resistance of chemotherapy in early-stage triple negative breast cancer (TNBC).

    Science.gov (United States)

    Wein, Lironne; Loi, Sherene

    2017-08-01

    Triple negative breast cancer (TNBC) a clinically aggressive subtype of breast cancer with poor outcomes. Chromosomal instability is a hallmark of many TNBCs, and likely underlies its ability to adapt and rapidly become resistant to chemotherapy. A study of residual disease after neoadjuvant chemotherapy have identified biological mechanisms driving this resistance to chemotherapy. Copy number amplifications such as MCL1, MYC and JAK2, as well as PTEN deletions or mutations have all been identified at a higher frequency in residual disease, suggesting they may play a role in de novo or acquired chemotherapy resistance. Increased copy number and expression of the PIM1 proto-oncogene in TNBC has also been identified as a new target of chemotherapy resistance. However, given the genomic instability and subclonal nature of driver mutations in TNBC, single agent targeted therapy is unlikely to be effective. Lately immune evasion has also been identified as another key characteristic of poor prognostic and chemo-resistant primary TNBCs. Combinations of checkpoint inhibition with targeted therapy and/or chemotherapy are currently being investigated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer.

    Science.gov (United States)

    Yang, Su-Jin; Wang, Dan-Dan; Li, Jian; Xu, Han-Zi; Shen, Hong-Yu; Chen, Xiu; Zhou, Si-Ying; Zhong, Shan-Liang; Zhao, Jian-Hua; Tang, Jin-Hai

    2017-08-05

    Anthracycline/taxane-based chemotherapy regimens are usually used as neoadjuvant chemotherapies to decrease tumour size and prevent metastasis of advanced breast cancer. However, patients have a high risk of developing chemo-resistance during treatment through still unknown mechanisms. Glutathione S-transferase P1 (GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione. Previous studies have identified GSTP1 as a predictor of prognosis and chemo-resistance in breast cancer patients, but the mechanisms governing GSTP1-dependent drug resistance are still unclear. We have found that GSTP1 expression is much higher in adriamycin-resistant cells and their corresponding exosomes. The role of GSTP1-containing exosomes in conferring drug resistance was analysed through cell apoptosis and immunofluorescence staining assays. Furthermore, we analysed 42 cases of paired breast cancer tissues collected before and after anthracycline/taxane-based neoadjuvant chemotherapy by immunohistochemistry. Higher GSTP1 expression was shown in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in the samples collected before and after the chemotherapy treatment. Interestingly, GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon treatment, and similar results were obtained for the exosomal marker Tumour susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. After analysing the serum exosomes of 30 patients treated with anthracycline/taxane-based neoadjuvant chemotherapy, we discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were significantly higher than those in the PR/CR group. Here, for the first time, we investigated a novel role for GSTP1-containing exosomes and their capability to transfer drug resistance

  9. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana

    2017-01-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated...

  10. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist).

    Science.gov (United States)

    Lindemann, Kristina; Gibbs, Emma; Åvall-Lundqvist, Elisabeth; dePont Christensen, Rene; Woie, Kathrine; Kalling, Marten; Auranen, Annika; Grenman, Seija; Hoegberg, Thomas; Rosenberg, Per; Skeie-Jensen, Tone; Hjerpe, Elisabet; Dørum, Anne; Gebski, Val; Kristensen, Gunnar

    2017-02-14

    Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m-2 or four weekly pegylated liposomal doxorubicin 40 mg m-2) or tamoxifen 40 mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P=0.003). There was no difference in OS between the treatment arms. Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.

  11. Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer.

    Science.gov (United States)

    Wang, X; Zuo, D; Chen, Y; Li, W; Liu, R; He, Y; Ren, L; Zhou, L; Deng, T; Wang, X; Ying, G; Ba, Y

    2014-11-11

    Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported. We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence. Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling. Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer.

  12. SIRT1/PGC1a-dependent increase in oxidative phosphorylation supports chemotherapy resistance of colon cancer

    NARCIS (Netherlands)

    Vellinga, T.T.; Borovski, T.; Boer, de V.C.J.; Kranenburg, O.

    2015-01-01

    PURPOSE:
    Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms.
    EXPERIMENTAL DESIGN:
    We studied gene expression

  13. Nanotechnology-based treatment for chemotherapy-resistant breast cancer

    Science.gov (United States)

    Abouzeid, Abraham H.; Patel, Niravkumar R.; Rachman, Ilya M.; Senn, Sean; Torchilin, Vladimir P.

    2014-08-01

    Background: Treatment of metastatic cancer remains a formidable clinical challenge. Better therapeutic options with improved tissue penetration and tumor cell uptake are urgently needed. Targeted nanotherapy, for improved delivery, and combinatory drug administration aimed at inhibiting chemo-resistance may be the solution. Purpose: The study was performed to evaluate the therapeutic efficacy of polymeric PEG-PE micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against MDA-MB-231 human breast adenocarcinoma cells both in vitro and in vivo. Methods: MDA-MB-231 DOX-resistant cells were treated with non-targeted and GLUT1-targeted CUR and DOX micelles as a single agent or in combination. Tumor cells were also inoculated in female nude mice. Established tumors were treated with the micellar formulations at a dose of 6 mg/kg CUR and 1 mg/kg DOX every 2 d for a total of 7 injections. Results: CUR+DOX-loaded micelles decorated with GLUT1 had a robust killing effect even at low doses of DOX in vitro. At the doses chosen, non-targeted CUR and CUR+DOX micelles did not exhibit significant tumor inhibition versus control. However, GLUT1-CUR and GLUT1-CUR+DOX micelles showed a significant tumor inhibition effect with an improvement in survival. Conclusion: We showed a dramatic improvement in efficacy between the non-targeted and GLUT1-targeted formulations both in vitro and in vivo. Also, importantly, the addition of CUR to the micelle, has restored sensitivity to DOX, with resultant tumor growth inhibition. Hence, we confirmed that GLUT1-CUR+DOX micelles are effective in vitro and in vivo and deserve further investigation.

  14. Macrophages induce resistance to 5-fluorouracil chemotherapy in colorectal cancer through the release of putrescine.

    Science.gov (United States)

    Zhang, Xuan; Chen, Yujuan; Hao, Lijun; Hou, Along; Chen, Xiaozhen; Li, Yifei; Wang, Rui; Luo, Peng; Ruan, Zhihua; Ou, Juanjuan; Shi, Chunmeng; Miao, Hongming; Liang, Houjie

    2016-10-28

    The development of chemoresistance to 5-fluorouracil (5-FU) is a major obstacle for sustained effective treatment of colorectal cancer (CRC), with the mechanisms being not fully understood. Here we demonstrated that tumor associated macrophages (TAMs) became activated during treatment with 5-FU and secreted factors that protected the CRC cells against chemotherapy with 5-FU. By performing metabolomics analysis, we identified putrescine, a member of polyamines, inducing resistance to 5-FU-triggered CRC apoptosis and tumor suppression via JNK-caspase-3 pathway. Noteworthily, either pharmacological or genetic blockage of ornithine decarboxylase (ODC) prevented TAMs-induced chemoresistance to 5-FU in vitro and in vivo. Our findings show that TAMs are potent mediators of resistance to 5-FU chemotherapy and uncover potential targets to enhance chemotherapy sensitivity in patients with CRC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Prediction of resistance to chemotherapy in ovarian cancer: a systematic review.

    Science.gov (United States)

    Lloyd, Katherine L; Cree, Ian A; Savage, Richard S

    2015-03-11

    Patient response to chemotherapy for ovarian cancer is extremely heterogeneous and there are currently no tools to aid the prediction of sensitivity or resistance to chemotherapy and allow treatment stratification. Such a tool could greatly improve patient survival by identifying the most appropriate treatment on a patient-specific basis. PubMed was searched for studies predicting response or resistance to chemotherapy using gene expression measurements of human tissue in ovarian cancer. 42 studies were identified and both the data collection and modelling methods were compared. The majority of studies utilised fresh-frozen or formalin-fixed paraffin-embedded tissue. Modelling techniques varied, the most popular being Cox proportional hazards regression and hierarchical clustering which were used by 17 and 11 studies respectively. The gene signatures identified by the various studies were not consistent, with very few genes being identified by more than two studies. Patient cohorts were often noted to be heterogeneous with respect to chemotherapy treatment undergone by patients. A clinically applicable gene signature capable of predicting patient response to chemotherapy has not yet been identified. Research into a predictive, as opposed to prognostic, model could be highly beneficial and aid the identification of the most suitable treatment for patients.

  16. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Madsen, Christine Vestergaard; Andersen, Rikke Fredslund

    2014-01-01

    AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment...... of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance...

  17. Chemotherapy to Treat Cancer

    Science.gov (United States)

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  18. Expression of multidrug resistance proteins P-glycoprotein, multidrug resistance protein 1, breast cancer resistance protein and lung resistance related protein in locally advanced bladder cancer treated with neoadjuvant chemotherapy: biological and clinical implications.

    NARCIS (Netherlands)

    Diestra, JE; Condom, E; Muro, XG Del; Scheffer, G.L.; Perez, J; Zurita, AJ; Munoz-Segui, J; Vigues, F; Scheper, R.J.; Capella, G; Germa-Lluch, JR; Izquierdo, M.A.

    2003-01-01

    PURPOSE: Resistance to chemotherapy is a major obstacle to overcome in the conservative treatment of patients with locally advanced bladder cancer (LABC). We investigated the predictive value of the response to neoadjuvant chemotherapy (NACT) and prognosis of the expression of multidrug resistance

  19. Natural products to prevent drug resistance in cancer chemotherapy: a review.

    Science.gov (United States)

    Yuan, Renyikun; Hou, Ying; Sun, Wen; Yu, Jie; Liu, Xin; Niu, Yanan; Lu, Jin-Jian; Chen, Xiuping

    2017-08-01

    Chemotherapy is the standard internal medical treatment for cancer. However, the resistance of cancer cells to nearly all kinds of chemotherapeutic drugs and targeted drugs has become prevalent, and approximately 80-90% of deaths in cancer patients are directly or indirectly attributed to drug resistance. The progress of new drug research and development has also been impeded by the occurrence of drug resistance, which has emerged as a considerable challenge in cancer therapy. Fortunately, natural products with diverse chemical structures and pharmacological effects serve as effective substances against drug resistance. Since the discovery of a series of drug-resistant proteins, drug-efflux inhibition has been applied as the primary strategy to overcome drug resistance by maintaining the intracellular concentrations of chemotherapeutic drugs. Nonapoptotic cell death is considered an alternative strategy because most cases of drug resistance result in evasion and insensitivity to apoptosis. In this concise review, we summarize two strategies using natural products against drug resistance. © 2017 New York Academy of Sciences.

  20. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Tolver, Anders

    2014-01-01

    Abstract Background: Bleomycin–etoposid–cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety...... and efficacy of resistance training to modulate these changes. Methods: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3...... changes compared with the INT-group (PBEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP...

  1. An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy.

    Science.gov (United States)

    Takara, Kohji; Sakaeda, Toshiyuki; Okumura, Katsuhiko

    2006-01-01

    The intrinsic or acquired resistance to anticancer drugs remains one of the most significant factors impeding the progress of cancer chemotherapy. This phenomenon often involves simultaneous resistance to other anticancer drugs that differ in their chemical structure and mode of action and are not even used in chemotherapy. This phenotype has been called multidrug resistance (MDR). Although the cellular basis underlying MDR is not fully understood, several factors mediating therapy resistance in tumors have been proposed. One of the mechanisms leading to chemoresistance of tumor cells is the increased activity of transporter proteins. The best-characterized transporter protein is MDR1/P-glycoprotein, and a number of clinical investigations have suggested that its intrinsic or acquired overexpression resulted in a poor clinical outcome of chemotherapy. Various types of compounds and techniques for the reversal of MDR1/P-glycoprotein-mediated MDR have been developed, and efforts have concentrated on the inhibition of function and suppression of expression. This review summarizes the current state of knowledge of MDR1/P-glycoprotein and the modulation of MDR by targeting MDR1/P-glycoprotein.

  2. Budget Impact of Enzalutamide for Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Bui, Cat N; O'Day, Ken; Flanders, Scott; Oestreicher, Nina; Francis, Peter; Posta, Linda; Popelar, Breanna; Tang, Hong; Balk, Mark

    2016-02-01

    Prostate cancer is expected to account for approximately one quarter of all new diagnoses of cancer in American men in 2015. The cost of prostate cancer care is expected to reach $15.1 billion by the year 2020, up from $11.9 billion in 2010. Given the high burden of prostate cancer, health care payers are interested in quantifying the potential budget impact of new therapies. To estimate the budget impact of enzalutamide for the treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) from a U.S. payer perspective. A model was developed to assess the budget impact of enzalutamide for treatment of chemotherapy-naïve mCRPC patients in a hypothetical 1-million-member U.S. health plan over a 1-year time horizon. Comparators included abiraterone acetate, sipuleucel-T, radium Ra 223 dichloride, and docetaxel. Epidemiologic data, including National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) incidence rates, were used to estimate the number of chemotherapy-naïve mCRPC patients. Dosing, administration, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. Drug costs were obtained from RED BOOK and Centers for Medicare & Medicaid Services (CMS) average sales price pricing files, costs of administration and monitoring from the CMS physician fee schedule, and adverse events from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and published literature. Market shares were estimated for each comparator before and after adoption of enzalutamide. The incremental aggregate budget impact, per patient per year (PPPY), per patient per month (PPPM), and per member per month (PMPM), was calculated. One-way sensitivity analyses were performed. In a population of 115 chemotherapy-naïve mCRPC patients, adopting enzalutamide had an annual incremental budget impact of $510,641 ($4,426 PPPY, $369 PPPM, and $0.04 PMPM). Results were most sensitive to

  3. Intermittent docetaxel chemotherapy as first-line treatment for metastatic castration-resistant prostate cancer patients.

    Science.gov (United States)

    Caffo, Orazio; Lo Re, Giovanni; Sava, Teodoro; Buti, Sebastiano; Sacco, Cosimo; Basso, Umberto; Zustovich, Fable; Lodde, Michele; Perin, Alessandra; Facchini, Gaetano; Veccia, Antonello; Maines, Francesca; Barile, Carmen; Fratino, Lucia; Gernone, Angela; De Vivo, Rocco; Pappagallo, Giovanni L; Galligioni, Enzo

    2015-01-01

    The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. All patients received DOC 70 mg/m(2) every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL.

  4. Prospects of 2nd line chemotherapy personalization in patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is one of the most challenging and pressing problems of modern oncourology because of high morbidity associated with the disease worldwide. About 1 100 000 new cases are diagnosed each year. The main approach to treatment of locally advanced and/or metastatic PC is hormonal therapy. Androgen deprivation therapy allows to achieve stabilization in more than 90 % of patients, but average time until progression after hormonal therapy in patients with metastatic PC is about 2 years. Then patients with tumor progression accompanied by castration level of testosterone enter the stage of so-called castration-resistant PC (CRPC. Prognosis for regional CRPC is unfavorable, and it substantially lowers patients’ quality of life. Taxane-based chemotherapy remains a standard method of treatment in this patient cohort. The article reviews studies of efficacy of different doses and regimes of 2nd line chemotherapy using cabazitaxel in patients with metastatic CRPC.

  5. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    Directory of Open Access Journals (Sweden)

    Benitez-Bribiesca Luis

    2006-08-01

    Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

  6. Therapy's shadow: a short history of the study of resistance to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Peter eKeating

    2013-05-01

    Full Text Available This article traces the history of research on resistance to drug therapy in oncology usingscientometric techniques and qualitative analysis. Using co-citation analysis, we generatemaps to visualize subdomains in resistance research in two time periods, 1975-1990 and1995-2010. These maps reveal two historical trends in resistance research: first, a shift infocus from generic mechanisms of resistance to chemotherapy to a focus on resistance totargeted therapies and molecular mechanisms of oncogenesis; and second, a movementaway from an almost exclusive reliance on animal and cell models and towards thegeneration of knowledge about resistance through clinical trial work. A close reading ofhighly cited articles within each subdomain cluster reveals specific points of transitionfrom one regime to the other, in particular the failure of several promising theories ofresistance to be translated into clinical insights and the emergence of interest in resistanceto a new generation of targeted agents such as imatinib and trastuzumab. We argue thatthe study of resistance in the oncology field has thus become more integrated withresearch into cancer therapy—rather than constituting it as a separate domain of study, asit has done in the past, contemporary research treats resistance as the flip side totreatment, as therapy’s shadow.

  7. In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies.

    Science.gov (United States)

    McDermott, Martina; Eustace, Alex J; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O'Donovan, Norma; Stordal, Britta

    2014-01-01

    The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical

  8. Breast Cancer-Targeted Nuclear Drug Delivery Overcoming Drug Resistance for Breast Cancer Chemotherapy

    Science.gov (United States)

    2010-09-01

    cancer therapy. J Nanobiotechnol 2007;5(3):1e18. [34] Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate -chitosan- pluronic composite...absorbance at 486 nm in DMSO/methanol. The encapsulation efficiency was 78% and the loading content was 14.3%. MALDI-TOF spectra: α-cyano-4...is agreeable with the reports that curcumin could potentiate chemotherapy [24,25]. The cellular uptake of free and encapsulated DOX was observed by

  9. Cyclin A correlates with YB1, progression and resistance to chemotherapy in human epithelial ovarian cancer.

    Science.gov (United States)

    Cybulski, Marek; Jarosz, Bożena; Nowakowski, Andrzej; Jeleniewicz, Witold; Kutarska, Elżbieta; Bednarek, Wiesława; Stepulak, Andrzej

    2015-03-01

    Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy. Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues. Immunolabeling of both proteins was graded according to their staining intensity (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to obtain a staining index (SI; value=0-12). Significantly higher cyclin A immunostaining (SI≥4) in EOC specimens was discovered in patients with advanced (International Federation of Gynaecology and Obstetrics (FIGO) III and IV, p=0.003), poorly differentiated (G3, p1 cm (p=0.001). YB1 immunostaining was significantly higher in EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin A (SI≥9) in EOCs was significantly linked with poorer patient response (p=0.001) and higher resistance of tumors to platinum-based first-line chemotherapy (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated with either of these variables (p>0.05). Cyclin A expression was significantly and positively correlated with that of YB1 (R=0.588, p<0.001). Increased cyclin A expression in EOC is related to a more aggressive tumor behavior and predicts the response of patients to first-line platinum-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  11. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial

    OpenAIRE

    Christensen, J F; Jones, L W; Tolver, A.; J?rgensen, L W; Andersen, J. L.; Adamsen, L; H?jman, P; Nielsen, R.H.; R?rth, M; Daugaard, G.

    2014-01-01

    Background: Bleomycin?etoposid?cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. Methods: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks...

  12. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance

    Science.gov (United States)

    Balko, Justin M; Cook, Rebecca S; Vaught, David B; Kuba, María G; Miller, Todd W; Bhola, Neil E; Sanders, Melinda E; Granja-Ingram, Nara M; Smith, J Joshua; Meszoely, Ingrid M; Salter, Janine; Dowsett, Mitch; Stemke-Hale, Katherine; González-Angulo, Ana M; Mills, Gordon B; Pinto, Joseph A; Gómez, Henry L; Arteaga, Carlos L

    2012-01-01

    Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy. PMID:22683778

  13. MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation.

    Science.gov (United States)

    Lee, Kyung-Min; Giltnane, Jennifer M; Balko, Justin M; Schwarz, Luis J; Guerrero-Zotano, Angel L; Hutchinson, Katherine E; Nixon, Mellissa J; Estrada, Mónica V; Sánchez, Violeta; Sanders, Melinda E; Lee, Taekyu; Gómez, Henry; Lluch, Ana; Pérez-Fidalgo, J Alejandro; Wolf, Melissa Magdalene; Andrejeva, Gabriela; Rathmell, Jeffrey C; Fesik, Stephen W; Arteaga, Carlos L

    2017-10-03

    Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of activated mtOXPHOS, led to the accumulation of HIF-1α. Pharmacological inhibition of HIF-1α attenuated CSC enrichment and tumor initiation in vivo. These data suggest that (1) MYC and MCL1 confer resistance to chemotherapy by expanding CSCs via mtOXPHOS and (2) targeting mitochondrial respiration and HIF-1α may reverse chemotherapy resistance in TNBC. Copyright © 2017. Published by Elsevier Inc.

  14. Platinum-based chemotherapy for variant castrate-resistant prostate cancer.

    Science.gov (United States)

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

    2013-07-01

    Clinical features characteristic of small-cell prostate carcinoma (SCPC), "anaplastic," often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined "anaplastic" clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy. A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after four cycles of CD and EP, respectively. Median overall survival (OS) was 16 months [95% confidence interval (CI), 13.6-19.0 months]. Of the seven "anaplastic" criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Our findings support the hypothesis that patients with "anaplastic" prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with castration-resistant prostate cancer and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population. ©2013 AACR.

  15. Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.

    Science.gov (United States)

    Zhang, Shumin; Wang, Yanru; Chen, Zhengjia; Kim, Sungjin; Iqbal, Shareen; Chi, Andrew; Ritenour, Chad; Wang, Yongqiang A; Kucuk, Omer; Wu, Daqing

    2013-11-01

    Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models. The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models. Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis. This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC. © 2013 Wiley Periodicals, Inc.

  16. A metastatic castration resistant prostate cancer patient with multiple bone metastases has durable biochemical and radiological response to docetaxel chemotherapy

    Science.gov (United States)

    Daimon, Tatsuaki; Kosaka, Takeo; Oya, Mototsugu

    2016-01-01

    Docetaxel chemotherapy for metastatic castration resistant prostate cancer patients has been thought palliative because the radiological response rate is low and durable response is rare. The patient was a 64-year-old man who was diagnosed with cT3aN0M0 prostate cancer and underwent external beam radiation therapy as the initial treatment. He underwent androgen deprivation therapy and 8 cycles of docetaxel chemotherapy. His PSA level decreased and became undetectable and the disease was confirmed to be stable by radiological examination. We report a rare case that a metastatic castration resistant prostate cancer patient with multiple bone metastases has durable radiological and biochemical response. PMID:27766278

  17. Neoadjuvant chemotherapy induces expression levels of breast cancer resistance protein that predict disease-free survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Baek Kim

    Full Text Available Three main xenobiotic efflux pumps have been implicated in modulating breast cancer chemotherapy responses. These are P-glycoprotein (Pgp, Multidrug Resistance-associated Protein 1 (MRP1, and Breast Cancer Resistance Protein (BCRP. We investigated expression of these proteins in breast cancers before and after neoadjuvant chemotherapy (NAC to determine whether their levels define response to NAC or subsequent survival. Formalin-fixed paraffin-embedded tissues were collected representing matched pairs of core biopsy (pre-NAC and surgical specimen (post-NAC from 45 patients with invasive ductal carcinomas. NAC regimes were anthracyclines +/- taxanes. Immunohistochemistry was performed for Pgp, MRP1 and BCRP and expression was quantified objectively using computer-aided scoring. Pgp and MRP1 were significantly up-regulated after exposure to NAC (Wilcoxon signed-rank p = 0.0024 and p<0.0001, while BCRP showed more variation in response to NAC, with frequent up- (59% of cases and down-regulation (41% contributing to a lack of significant difference overall. Pre-NAC expression of all markers, and post-NAC expression of Pgp and MRP1 did not correlate with NAC response or with disease-free survival (DFS. Post-NAC expression of BCRP did not correlate with NAC response, but correlated significantly with DFS (Log rank p = 0.007, with longer DFS in patients with low post-NAC BCRP expression. In multivariate Cox regression analyses, post-NAC BCRP expression levels proved to predict DFS independently of standard prognostic factors, with high expression associated with a hazard ratio of 4.04 (95% confidence interval 1.3-12.2; p = 0.013. We conclude that NAC-induced expression levels of BCRP predict survival after NAC for breast cancer, while Pgp and MRP1 expression have little predictive value.

  18. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

    DEFF Research Database (Denmark)

    Jensen, Niels F.; Stenvang, Jan; Beck, Mette Kristina

    2015-01-01

    Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mecha......Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights......-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance...

  19. Dual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells.

    Science.gov (United States)

    Cocco, Emiliano; Deng, Yang; Shapiro, Erik M; Bortolomai, Ileana; Lopez, Salvatore; Lin, Ken; Bellone, Stefania; Cui, Jiajia; Menderes, Gulden; Black, Jonathan D; Schwab, Carlton L; Bonazzoli, Elena; Yang, Fan; Predolini, Federica; Zammataro, Luca; Altwerger, Gary; de Haydu, Christopher; Clark, Mitchell; Alvarenga, Julio; Ratner, Elena; Azodi, Masoud; Silasi, Dan-Arin; Schwartz, Peter E; Litkouhi, Babak; Saltzman, W Mark; Santin, Alessandro D

    2017-02-01

    Ovarian cancer is the most lethal gynecologic cancer. Claudin-3 and -4, the receptors for Clostridium perfringens enterotoxin (CPE), are overexpressed in more than 70% of these tumors. Here, we synthesized and characterized poly(lactic-co-glycolic-acid) (PLGA) nanoparticles (NPs) modified with the carboxy-terminal-binding domain of CPE (c-CPE-NP) for the delivery of suicide gene therapy to chemotherapy-resistant ovarian cancer cells. As a therapeutic payload, we generated a plasmid encoding for the diphtheria toxin subunit-A (DT-A) under the transcriptional control of the p16 promoter, a gene highly differentially expressed in ovarian cancer cells. Flow cytometry and immunofluorescence demonstrated that c-CPE-NPs encapsulating the cytomegalovirus (CMV) GFP plasmid (CMV GFP c-CPE-NP) were significantly more efficient than control NPs modified with a scrambled peptide (CMV GFP scr-NP) in transfecting primary chemotherapy-resistant ovarian tumor cell lines in vitro (P = 0.03). Importantly, c-CPE-NPs encapsulating the p16 DT-A vector (p16 DT-A c-CPE-NP) were significantly more effective than control p16 DT-A scr-NP in inducing ovarian cancer cell death in vitro (% cytotoxicity: mean ± SD = 32.9 ± 0.15 and 7.45 ± 7.93, respectively, P = 0.03). In vivo biodistribution studies demonstrated efficient transfection of tumor cells within 12 hours after intraperitoneal injection of CMV GFP c-CPE-NP in mice harboring chemotherapy-resistant ovarian cancer xenografts. Finally, multiple intraperitoneal injections of p16 DT-A c-CPE-NP resulted in a significant inhibition of tumor growth compared with control NP in chemotherapy-resistant tumor-bearing mice (P = 0.041). p16 DT-A c-CPE-NP may represent a novel dual-targeting therapeutic approach for the selective delivery of gene therapy to chemotherapy-resistant ovarian cancer cells. Mol Cancer Ther; 16(2); 323-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Chemotherapy in eye cancer

    African Journals Online (AJOL)

    Chemotherapy in eye cancer. Chemotherapy is one of several treatment strategies used to halt the uncontrolled division, proliferation and unpredictable growth patterns of malignant cells. R Dolland, BSc, MB BCh, FC Ophth (SA). Consultant, St John Eye Hospital, Division of Ophthalmology, Department of Neurosciences, ...

  1. HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

    2016-01-01

    The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

  2. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer

    DEFF Research Database (Denmark)

    Szallasi, Zoltan Imre; Li, Yang; Zou, Lihua

    2010-01-01

    the association in an analysis of multiple independent cohorts. SiRNA-mediated knockdown of either of two of these genes, the antiapoptotic gene YWHAZ and a lysosomal gene LAPTM4B, sensitized tumor cells to anthracyclines, and overexpression of either of the genes induced anthracycline resistance. Overexpression...... chemotherapy drugs is a challenge but is necessary to improve outcomes. By using integrated genomics, we identified a small number of overexpressed and amplified genes from chromosome 8q22 that were associated with early disease recurrence despite anthracycline-based adjuvant chemotherapy. We confirmed...

  3. Co-introduction of a steroid with docetaxel chemotherapy for metastatic castration-resistant prostate cancer affects PSA flare.

    Science.gov (United States)

    Shiota, Masaki; Yokomizo, Akira; Takeuchi, Ario; Kiyoshima, Keijiro; Inokuchi, Junichi; Tatsugami, Katsunori; Shiga, Ken-Ichiro; Koga, Hirofumi; Yamaguchi, Akito; Naito, Seiji; Eto, Masatoshi

    2016-12-01

    To investigate the potential relationship of steroid usage with prostate-specific antigen (PSA) flare as well as the prognostic impact of PSA flare, which is known to occur in 10-20% of patients with metastatic castration-resistant prostate cancer during docetaxel chemotherapy. This study included 71 patients with metastatic castration-resistant prostate cancer treated by docetaxel chemotherapy with co-introduction of a steroid. PSA flare was defined as a transient PSA increase followed by a PSA decrease. PSA flare was recognized in 7.0-23.9% of patients according to the definition used. Intriguingly, men with steroid intake before the initiation of docetaxel chemotherapy experienced significantly fewer PSA flares. The progression-free survival rate in men with PSA flare was equivalent to that of PSA responders, but significantly better than men with PSA failure. Our results suggest that de novo steroid co-introduction with docetaxel chemotherapy induces the PSA flare phenomenon. This novel finding may account for the mechanism of PSA flare as well as being valuable for distinguishing PSA elevation attributable to PSA flare from that attributable to PSA failure. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  4. Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism.

    Science.gov (United States)

    Liao, Jianqun; Qian, Feng; Tchabo, Nana; Mhawech-Fauceglia, Paulette; Beck, Amy; Qian, Zikun; Wang, Xinhui; Huss, Wendy J; Lele, Shashikant B; Morrison, Carl D; Odunsi, Kunle

    2014-01-01

    Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >10(5) parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. (13)C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy.

  5. Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer-The GCIG Symptom Benefit Study.

    Science.gov (United States)

    Roncolato, Felicia T; Joly, Florence; O'Connell, Rachel; Lanceley, Anne; Hilpert, Felix; Buizen, Luke; Okamoto, Aikou; Aotani, Eriko; Pignata, Sandro; Donnellan, Paul; Oza, Amit; Avall-Lundqvist, Elisabeth; Berek, Jonathan S; Heitz, Florian; Feeney, Amanda; Berton-Rigaud, Dominique; Stockler, Martin R; King, Madeleine; Friedlander, Michael

    2017-09-01

    Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. This study enrolled women with PRROC before starting palliative chemotherapy. Health-related quality of life was measured with EORTC QLQ-C30/QLQ-OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression-free and OS. Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all p Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self-ratings of GHS, RF, and PF could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC. Measuring aspects of health-related quality of life when considering further chemotherapy in platinum resistant/refractory ovarian cancer (PRROC) could help identify women with a particularly poor prognosis who are unlikely to benefit from chemotherapy and could therefore be spared unnecessary treatment and toxicity in their last months of life. Self-ratings of global health status, role function, and physical function could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC. © AlphaMed Press 2017.

  6. A Combination of Immune Checkpoint Inhibition with Metronomic Chemotherapy as a Way of Targeting Therapy-Resistant Cancer Cells

    Directory of Open Access Journals (Sweden)

    Irina Kareva

    2017-10-01

    Full Text Available Therapeutic resistance remains a major obstacle in treating many cancers, particularly in advanced stages. It is likely that cytotoxic lymphocytes (CTLs have the potential to eliminate therapy-resistant cancer cells. However, their effectiveness may be limited either by the immunosuppressive tumor microenvironment, or by immune cell death induced by cytotoxic treatments. High-frequency low-dose (also known as metronomic chemotherapy can help improve the activity of CTLs by providing sufficient stimulation for cytotoxic immune cells without excessive depletion. Additionally, therapy-induced removal of tumor cells that compete for shared nutrients may also facilitate tumor infiltration by CTLs, further improving prognosis. Metronomic chemotherapy can also decrease the number of immunosuppressive cells in the tumor microenvironment, including regulatory T cells (Tregs and myeloid-derived suppressor cells (MDSCs. Immune checkpoint inhibition can further augment anti-tumor immune responses by maintaining T cells in an activated state. Combining immune checkpoint inhibition with metronomic administration of chemotherapeutic drugs may create a synergistic effect that augments anti-tumor immune responses and clears metabolic competition. This would allow immune-mediated elimination of therapy-resistant cancer cells, an effect that may be unattainable by using either therapeutic modality alone.

  7. A Combination of Immune Checkpoint Inhibition with Metronomic Chemotherapy as a Way of Targeting Therapy-Resistant Cancer Cells.

    Science.gov (United States)

    Kareva, Irina

    2017-10-13

    Therapeutic resistance remains a major obstacle in treating many cancers, particularly in advanced stages. It is likely that cytotoxic lymphocytes (CTLs) have the potential to eliminate therapy-resistant cancer cells. However, their effectiveness may be limited either by the immunosuppressive tumor microenvironment, or by immune cell death induced by cytotoxic treatments. High-frequency low-dose (also known as metronomic) chemotherapy can help improve the activity of CTLs by providing sufficient stimulation for cytotoxic immune cells without excessive depletion. Additionally, therapy-induced removal of tumor cells that compete for shared nutrients may also facilitate tumor infiltration by CTLs, further improving prognosis. Metronomic chemotherapy can also decrease the number of immunosuppressive cells in the tumor microenvironment, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Immune checkpoint inhibition can further augment anti-tumor immune responses by maintaining T cells in an activated state. Combining immune checkpoint inhibition with metronomic administration of chemotherapeutic drugs may create a synergistic effect that augments anti-tumor immune responses and clears metabolic competition. This would allow immune-mediated elimination of therapy-resistant cancer cells, an effect that may be unattainable by using either therapeutic modality alone.

  8. Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Hong-mei ZHANG

    2015-11-01

    Full Text Available Objective To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission group, SD (stable disease group and PD (progressive disease group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%, SD in 25(48.1%, PD in 6(11.5%. In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P<0.05. Conclusions The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance. DOI: 10.11855/j.issn.0577-7402.2015.10.09

  9. Toward Maximizing Immunotherapy in Metastatic Castration Resistant Prostate Cancer – Rationale for Combinatorial Approaches Using Chemotherapy

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2012-05-01

    Full Text Available Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellule product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine G-VAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true anti-tumor immunity.

  10. Toward maximizing immunotherapy in metastatic castration-resistant prostate cancer - rationale for combinatorial approaches using chemotherapy.

    Science.gov (United States)

    Slovin, Susan R

    2012-01-01

    Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellular product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine GVAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true antitumor immunity.

  11. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Willemse, Peter-Paul M; van der Meer, Rutger W; Burggraaf, Jacobus; van Elderen, Saskia G C; de Kam, Marieke L; de Roos, Albert; Lamb, Hildo J; Osanto, Susanne

    2014-03-01

    Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m(2) (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development

  12. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells.

    Science.gov (United States)

    Ali, Jennifer L; Lagasse, Brittany J; Minuk, Ainsley J; Love, Allison J; Moraya, Amani I; Lam, Linda; Arthur, Gilbert; Gibson, Spencer B; Morrison, Ludivine Coudière; Werbowetski-Ogilvie, Tamra E; Fu, Yangxin; Nachtigal, Mark W

    2015-03-01

    Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs or drug combinations that produce EOC cell death or resensitize drug resistant cells to standard chemotherapy may improve patient treatment. After conducting drug tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it is structural analogue LDN-193189 (LDN), these drugs were tested in a mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed a trend toward increased survival. In vitro experiments using cisplatin (CP)-resistant EOC cell lines, A2780-cp or SKOV3, we determined that pretreatment or cotreatment with DM or LDN resensitized cells to the killing effect of CP or carboplatin (CB). DM was capable of blocking EOC cell cycle and migration, whereas LDN produced a less pronounced effect on cell cycle and no effect on migration. Subsequent analyses using primary human EOC cell samples or additional established EOC cells lines showed that DM or LDN induced a dose-dependent autophagic or cell death response, respectively. DM induced a characteristic morphological change with the appearance of numerous LC3B-containing acidic vacuoles and an increase in LC3BII levels. This was coincident with a decrease in cell growth and the altered cell cycle consistent with DM-induced cytostasis. By contrast, LDN produced a caspase 3-independent, reactive oxygen species-dependent cell death. Overall, DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC. © 2014 UICC.

  13. Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy.

    Science.gov (United States)

    Incio, Joao; Liu, Hao; Suboj, Priya; Chin, Shan M; Chen, Ivy X; Pinter, Matthias; Ng, Mei R; Nia, Hadi T; Grahovac, Jelena; Kao, Shannon; Babykutty, Suboj; Huang, Yuhui; Jung, Keehoon; Rahbari, Nuh N; Han, Xiaoxing; Chauhan, Vikash P; Martin, John D; Kahn, Julia; Huang, Peigen; Desphande, Vikram; Michaelson, James; Michelakos, Theodoros P; Ferrone, Cristina R; Soares, Raquel; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K

    2016-08-01

    It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacologic inhibition of angiotensin-II type-1 receptor reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSC) in obesity is induced by tumor-associated neutrophils (TAN) recruited by adipocyte-secreted IL1β. PSCs further secrete IL1β, and inactivation of PSCs reduces IL1β expression and TAN recruitment. Furthermore, depletion of TANs, IL1β inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In patients with pancreatic cancer, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that cross-talk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity. Considering the current obesity pandemic, unraveling the mechanisms underlying obesity-induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity-promoted PDAC progression. Importantly, we discovered that clinically available antifibrotic/inflammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852-69. ©2016 AACR.See related commentary by Bronte and Tortora, p. 821This article is highlighted in the In This Issue feature, p. 803. ©2016 American Association for Cancer Research.

  14. Chemotherapy plus estramustine for management of castration-resistant prostate cancer: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, C; Jing, T; Wang, F; Gao, X; Xu, C; Sun, Y

    2014-04-01

    Estramustine, an agent with both hormonal and non-hormonal effects in men, is supposed to be effective in treating castration-resistant prostate cancer. However, previous studies have reported conflicting results. We conducted this meta-analysis to evaluate the efficacy and toxicity of additional estramustine to chemotherapy. Data sources including PubMed, Medline, EMBASE, and Cochrane Controlled Trials Register were searched to identify potentially relevant randomized controlled trials. Prostate specific antigen (PSA) response, overall survival, and grade 3 to 4 toxicity were analyzed. Seven randomized controlled trials, a total of 839 patients, were enrolled. The pooled odds ratio for PSA response was 3.02 (95% CI=1.69-5.39, P=.0002); the pooled hazard ratio for overall survival was .95 (95% CI=.80-1.14, P=.58); the pooled odds ratio for nausea/vomiting and cardiovascular toxicity were 3.90 (95% CI=1.05-14.45, P=.04) and 2.22 (95% CI=1.15-4.30, P=.02). No significant difference was detected for neutropenia, anemia, thrombocytopenia, diarrhea, fatigue, or neuropathy (P>.05). According to this meta-analysis, chemotherapy with additional estramustine increased the PSA response rate. However, it increased the risk of grade 3 or 4 adverse effects such as nausea/vomiting and cardiovascular events, and the overall survival was not improved for castration-resistant prostate cancer patients. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  15. Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebaek; Røder, Martin Andreas; Rathenborg, Per

    2014-01-01

    %). Forty-six percent had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate with the number of prior cancer treatments (p = 0.57), time from diagnosis to mCRPC (p = 0.11) or prior response to docetaxel (p = 0.67). However, patients treated with second line cabazitaxel......OBJECTIVE: The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post......-chemotherapy setting. MATERIAL AND METHODS: Twenty-four mCRPC patients with progression after abiraterone treatment following primary docetaxel therapy received enzalutamide 160 mg/day. The percentage PSA response was recorded following first line docetaxel, abiraterone and enzalutamide treatment. Fischer's exact test...

  16. Toward targeted therapy in chemotherapy-resistant pancreatic cancer with a smart triptolide nanomedicine.

    Science.gov (United States)

    Wang, Cheng; Liu, Biao; Xu, Xuelian; Zhuang, Bo; Li, Hongxia; Yin, Jiaqi; Cong, Mengyi; Xu, Wei; Lu, Aiping

    2016-02-16

    Chemoresistance is the major impediment for treating pancreatic cancer. Herb-derived compound triptolide (TP) can inhibit proliferation of chemo-resistant pancreatic cancer (CPC) cell lines through multiple mechanisms, which exhibited superior anticancer efficacy compared with gemcitabine. However, toxicity due to non-specific exposure to healthy tissues hindered its clinical translation. Herein we successfully achieved targeting CPC cells and avoiding exposure to healthy tissues for TP by nucleolin-specific aptamer (AS1411) mediated polymeric nanocarrier. We conjugated AS1411 aptamer to carboxy terminated poly(ethylene glycol)-block-poly(d, l-lactide) (HOOC-PEG-PDLLA), then prepared AS1411-PEG-PDLLA micelle loading TP (AS-PPT) through solid dispersion technique. AS-PPT showed more antitumor activity than TP and equivalent specific binding ability with gemcitabine-resistant human pancreatic cancer cell (MIA PaCa-2) to AS1411 aptamer in vitro. Furthermore, we studied the distribution of AS-PPT (Cy3-labed TP) at tissue and cellular levels using biophotonic imaging technology. The results showed AS1411 facilitated TP selectively accumulating in tumor tissues and targeting CPC cells. The lifetime of the MIA PaCa-2 cell-bearing mice administrated with AS-PPT was efficiently prolonged than that of the mice subjected to the clinical anticancer drug Gemzar® in vivo. Such work provides a new strategy for overcoming the drug resistance of pancreatic cancer.

  17. Mechanistic exploration of cancer stem cell marker voltage-dependent calcium channel α2δ1 subunit-mediated chemotherapy resistance in small cell lung cancer.

    Science.gov (United States)

    Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

    2018-02-06

    Chemo-resistance in small cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSCs). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. The current study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemo-resistant SCLC, and explored the potential mechanisms of α2δ1-mediated chemo-resistance and strategies of overcoming the resistance. α2δ1 positive cells were identified and isolated from SCLC cell lines and patient derived xenografts (PDXs) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western Blotting were carried out to identify pathways involved in α2δ1-mediated chemo-resistance in SCLC. Additionally, possible interventions to overcome ɑ2δ1 mediated chemo-resistance were examined. Different proportions of α2δ1+ cells were identified in SCLC cell lines and PDX models. ɑ2δ1 positive cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential and high-expression of genes related to CSCs and drug-resistance). Chemotherapy induced the enrichment of α2δ1+ cells instead of CD133+ cells in PDXs, and an increased proportion of α2δ1+ cells corresponded to increased chemo-resistance. Activation and over-expression of Erk in the ɑ2δ1 positive H1048 cell line was identified at the protein level. 1B50-1 mAb was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemo-resistance. Erk may play a key role in α2δ1 mediated chemo-resistance. 1B50-1 inhibitors may serve as potential anti-SCLC drugs. Copyright ©2018, American Association for Cancer Research.

  18. Primary tumor levels of tissue inhibitor of metalloproteinases-1 are predictive of resistance to chemotherapy in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Rasmussen, Anne-Sofie Schrohl; Meijer-van Gelder, Marion E.; Holten-Andersen, Mads N.

    2006-01-01

    PURPOSE: Only about 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy. Today, no validated markers exist for prediction of chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against...... tumor expression levels of TIMP-1 protein and objective response to first-line chemotherapy in 173 patients with metastatic breast cancer. RESULTS: When analyzed as a continuous log-transformed variable, increasing TIMP-1 levels were significantly associated with lack of response to cyclophosphamide...... TIMP-1, we identified a group of patients with metastatic breast cancer, which hardly respond to the most frequently used chemotherapy regimes (i.e., cyclophosphamide/methotrexate/5-fluorouracil and anthracyclines)....

  19. Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop.

    Science.gov (United States)

    Coffman, Lan G; Choi, Yun-Jung; McLean, Karen; Allen, Benjamin L; di Magliano, Marina Pasca; Buckanovich, Ronald J

    2016-02-09

    The tumor microenvironment is critical to cancer growth and therapy resistance. We previously characterized human ovarian carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are multi-potent cells that can differentiate into tumor microenvironment components including fibroblasts, myofibroblasts and adipocytes. We previously reported CA-MSCs, compared to normal MSCs, express high levels of BMP proteins and promote tumor growth by increasing numbers of cancer stem-like cells (CSCs). We demonstrate here that ovarian tumor cell-secreted Hedgehog (HH) induces CA-MSC BMP4 expression. CA-MSC-derived BMP4 reciprocally increases ovarian tumor cell HH expression indicating a positive feedback loop. Interruption of this loop with a HH pathway inhibitor or BMP4 blocking antibody decreases CA-MSC-derived BMP4 and tumor-derived HH preventing enrichment of CSCs and reversing chemotherapy resistance. The impact of HH inhibition was only seen in CA-MSC-containing tumors, indicating the importance of a humanized stroma. These results are reciprocal to findings in pancreatic and bladder cancer, suggesting HH signaling effects are tumor tissue specific warranting careful investigation in each tumor type. Collectively, we define a critical positive feedback loop between CA-MSC-derived BMP4 and ovarian tumor cell-secreted HH and present evidence for the further investigation of HH as a clinical target in ovarian cancer.

  20. The Role of Epigenetics in Resistance to Cisplatin Chemotherapy in Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    O' Byrne, Kenneth J.; Barr, Martin P.; Gray, Steven G., E-mail: sgray@stjames.ie [Trinity College Dublin, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James Hospital, James Street, Dublin 8 (Ireland)

    2011-03-17

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC.

  1. Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Castration-Resistant Prostate Cancer Patients Who Received Cabazitaxel Chemotherapy

    Directory of Open Access Journals (Sweden)

    Koichi Uemura

    2017-01-01

    Full Text Available Introduction and Objectives. An elevated neutrophil-to-lymphocyte ratio (NLR has been suggested to be associated with a poor prognosis in several cancers. We evaluated the utility of an elevated NLR as a biomarker to predict the prognosis of metastatic castration-resistant prostate cancer (mCRPC patients treated with cabazitaxel (CBZ. Methods. We analyzed 47 patients who received CBZ chemotherapy for mCRPC in our institutions. The NLR was calculated using the neutrophil and lymphocyte counts before CBZ chemotherapy. We determined the NLR cut-off value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. A multivariate analysis was performed to investigate the association between the NLR and the prognosis. Results. The median overall survival (OS after CBZ was 10.0 months (range: 6.3–13.2. The median OS was shorter in patients with a high NLR (≥3.83 than in those with a low NLR (<3.83 (5.8 versus 13.2 months, p=0.018. In the multivariate analysis, the NLR, patient age, and lymph node (LN metastasis were independent predictors of the OS (hazard ratio 3.01, p=0.030; hazard ratio 3.10, p=0.029; hazard ratio 12.38, p=0.001, resp.. Conclusions. NLR might be a useful prognostic biomarker in mCRPC patients treated with CBZ.

  2. A novel two mode-acting inhibitor of ABCG2-mediated multidrug transport and resistance in cancer chemotherapy.

    Directory of Open Access Journals (Sweden)

    Hui Peng

    2009-05-01

    Full Text Available Multidrug resistance (MDR is a major problem in successful treatment of cancers. Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in MDR and an important role in protecting cancer stem cells. Knockout of ABCG2 had no apparent adverse effect on the mice. Thus, ABCG2 is an ideal target for development of chemo-sensitizing agents for better treatment of drug resistant cancers and helping eradicate cancer stem cells.Using rational screening of representatives from a chemical compound library, we found a novel inhibitor of ABCG2, PZ-39 (N-(4-chlorophenyl-2-[(6-{[4,6-di(4-morpholinyl-1,3,5-triazin-2-yl]amino}-1,3-benzothiazol-2-ylsulfanyl]acetamide, that has two modes of actions by inhibiting ABCG2 activity and by accelerating its lysosome-dependent degradation. PZ-39 has no effect on ABCB1 and ABCC1-mediated drug efflux, resistance, and their expression, indicating that it may be specific to ABCG2. Analyses of its analogue compounds showed that the pharmacophore of PZ-39 is benzothiazole linked to a triazine ring backbone.Unlike any previously known ABCG2 transporter inhibitors, PZ-39 has a novel two-mode action by inhibiting ABCG2 activity, an acute effect, and by accelerating lysosome-dependent degradation, a chronic effect. PZ-39 is potentially a valuable probe for structure-function studies of ABCG2 and a lead compound for developing therapeutics targeting ABCG2-mediated MDR in combinational cancer chemotherapy.

  3. Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Kwon, Eugene D; Drake, Charles G

    2017-01-01

    Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Pat...

  4. Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-04

    We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression.

  5. Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jennifer Clark

    2012-01-01

    Full Text Available RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.

  6. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

    2013-09-15

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  7. Chemotherapy and anti-angiogenic drugs affect composition and coagulant phenotype of cell-derived vesicles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Verhoeff, J.; Berckmans, R.; Kunst, P.; Van Doormaal, F.; Di Nisio, M.; Richel, D.; Kamphuisen, P.W.; Büller, H.R.; Nieuwland, R.

    Background: The relationship between chemotherapy and circulating microparticles in patients with cancer is complex. First, release of cancer cell-derived microparticles may contribute to resistance of cancer cells to chemotherapy. Second, chemotherapy and angiogenesis inhibiting agents promote a

  8. Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Dong, Baijun; Fan, Liancheng; Wang, Yanqing; Chi, Chenfei; Ma, Xiaowei; Wang, Rui; Cai, Wen; Shao, Xiaoguang; Pan, Jiahua; Zhu, Yinjie; Shangguan, Xun; Xin, Zhixiang; Hu, Jianian; Xie, Shaowei; Kang, Xiaonan; Zhou, Lixin; Xue, Wei

    2017-05-01

    To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED. Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED. We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of m

  9. Progressive resistance versus relaxation training for breast cancer patients during adjuvant chemotherapy: design and rationale of a randomized controlled trial (BEATE study).

    Science.gov (United States)

    Schmidt, Martina E; Wiskemann, Joachim; Krakowski-Roosen, Holger; Knicker, Axel J; Habermann, Nina; Schneeweiss, Andreas; Ulrich, Cornelia M; Steindorf, Karen

    2013-01-01

    Cancer-related fatigue is a common severe symptom in breast cancer patients, especially during chemotherapy. Exercise appears to be promising in prevention or treatment of fatigue. Resistance training as an accompanying treatment to chemotherapy has been minimally investigated, yet might counteract muscle degradation and inflammation caused by many chemotherapeutics, and thus forestall or reduce fatigue. Previous exercise trials mostly compared the intervention with 'usual care'. Therefore, it is unclear to what extent the observed effects on fatigue are based on physical adaptations by exercise itself, or rather on psycho-social factors linked to the group support or attention by the trainer. The BEATE study is a randomized, controlled intervention trial comparing a 12-week supervised progressive resistance training program with a supervised group-based progressive muscle relaxation training in 100 patients with breast cancer under adjuvant chemotherapy. The primary endpoint is cancer-related fatigue; secondary endpoints include quality of life, depression, and cognitive capacity. In addition, isokinetic and isometric muscle strength, cardiorespiratory fitness, and body composition are measured, and biomarkers, such as inflammatory parameters, cortisol, and oxidative stress are analyzed in blood, saliva and urine. Safety of the resistance training during chemotherapy is monitored. Strengths of the BEATE study include the investigation of progressive resistance training parallel with chemotherapy, the choice of a control group that enables an evaluation of the physiological effects of exercise beyond potential psycho-social effects, and the comprehensive and high-quality assessment of physiological factors and biomarkers potentially related to fatigue. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Role of chemotherapy in prostate cancer.

    Science.gov (United States)

    Nader, Rita; El Amm, Joelle; Aragon-Ching, Jeanny B

    2017-10-20

    Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.

  11. Docetaxel based chemotherapy in the treatment of patients with castration resistant prostate cancer.

    Science.gov (United States)

    Mangir, N; Türkeri, L

    2014-10-01

    Docetaxel administered every 3- weeks is the standart treatment of castration resistant prostate cancer (CRPC) but it is associated with dose limiting toxicities. We analyzed the efficacy and tolerability of 3- weekly and weekly docetaxel in a Turkish cohort of CRPC patients with a special emphasis on the elderly patients. A retrospective analyses of 45 patients who received either 3- weekly or weekly docetaxel in a single urologic oncology clinic was performed. Response to therapy, toxicity and overall survival rates were evaluated. The mean age of patients was 70.0 (±8.8) years. Complete or partial PSA response was obtained in 45% of patients. The median overall survival was 20,0 months (SE 6.46; 95% CI 7,3-32,6). Absence of metastasis, time to CRPC>10 months, DP 75mg/m2 once every three weeks and PSA<50% at the end of the third cycle were associated with better overall survival. There was no significant survival difference between the patients aged 75 or older versus younger ones. The most common hematological toxicity was leukopenia which was dose limiting in only one patient. Administration of standart 3-weekly docetaxel is well tolerated in this relatively old cohort of Turkish CRPC patients and weekly administration can be a reasonable alternative in frail patients not only to prolong survival but also to palliate disease symptoms. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  12. STAT1‐associated intratumoural TH1 immunity predicts chemotherapy resistance in high‐grade serous ovarian cancer

    Science.gov (United States)

    Au, Katrina K; Le Page, Cécile; Ren, Runhan; Meunier, Liliane; Clément, Isabelle; Tyrishkin, Kathrin; Peterson, Nichole; Kendall‐Dupont, Jennifer; Childs, Timothy; Francis, Julie‐Ann; Graham, Charles H; Craig, Andrew W; Squire, Jeremy A; Mes‐Masson, Anne‐Marie

    2016-01-01

    Abstract High‐grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8+ T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8+ T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy‐naïve HGSCs. NanoString‐based profiling was performed to correlate expression of STAT1 target genes CXCL9, CXCL10 and CXCL11 with CD8A transcript expression in 143 primary tumours. Multiplexed cytokine analysis of pre‐treatment plasma from resistant and sensitive patients was performed to assess systemic levels of STAT1‐induced cytokines. STAT1 was validated as a prognostic and predictive biomarker in both univariate and multivariate models and its expression correlated significantly with intra‐epithelial CD8+ T cell infiltration in HGSC. STAT1 levels increased the prognostic and predictive value of intratumoural CD8+ T cells, confirming their synergistic role as biomarkers in HGSC. In addition, expression of STAT1 target genes (CXCL9, CXCL10 and CXCL11) correlated significantly with levels of, and CD8A transcripts from intratumoural CD8+ T cells within the resistant and sensitive tumours. Our findings provide compelling evidence that high levels of STAT1, STAT1‐induced chemokines and CD8+ T cells correlate with improved chemotherapy response in HGSC. These results identify STAT1 and its target genes as novel biomarkers of chemosensitivity in HGSC. These findings provide new translational opportunities for patient stratification for immunotherapies based on emerging biomarkers of inflammation in HGSC. An improved

  13. Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Antonarakis, Emmanuel S.; Lu, Changxue; Luber, Brandon; Wang, Hao; Chen, Yan; Nakazawa, Mary; Nadal, Rosa; Paller, Channing J.; Denmeade, Samuel R.; Carducci, Michael A.; Eisenberger, Mario A.; Luo, Jun

    2015-01-01

    IMPORTANCE We previously showed that detection of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) from men with castration-resistant prostate cancer (CRPC) was associated with primary resistance to enzalutamide and abiraterone therapy, but the relevance of AR-V7 status in the context of chemotherapy is unknown. OBJECTIVE To investigate whether AR-V7–positive patients would retain sensitivity to taxane chemotherapy and whether AR-V7 status would have a differential impact on taxane-treated men compared with enzalutamide- or abiraterone-treated men. DESIGN, SETTING, AND PARTICIPANTS We examined CTCs for AR-V7 mRNA using a reverse-transcription polymerase chain reaction assay. From January 2013 to July 2014, we prospectively enrolled patients with metastatic CRPC initiating taxane chemotherapy (docetaxel or cabazitaxel) at a single academic institution (Johns Hopkins). Our prespecified statistical plan required a sample size of 36 taxane-treated men. MAIN OUTCOMES AND MEASURES We evaluated associations between AR-V7 status and prostate-specific antigen (PSA) response rates. PSA progression-free survival (PSA PFS), and clinical and/or radiographic progression-free survival (PFS). After incorporating updated data from our prior study of 62 patients treated with enzalutamide or abiraterone, we also investigated the interaction between AR-V7 status (positive or negative) and treatment type (taxane vs enzalutamide or abiraterone). RESULTS Of 37 taxane-treated patients enrolled. 17 (46%) had detectable AR-V7 in CTCs. Prostate-specific antigen responses were achieved in both AR-V7–positive and AR-V7–negative men (41% vs 65%; P = .19) Similarly, PSA PFS (hazard ratio [HR], 1.7, 95% CI, 0.6-5.0; P = .32) and PFS (HR, 2.7, 95% CI, 0.8-8.8; P = .11) were comparable in AR-V7–positive and AR-V7–negative patients. A significant interaction was observed between AR-V7 status and treatment type (P < .001). Clinical outcomes were superior with

  14. P-glycoprotein-mediated resistance to chemotherapy in cancer cells: using recombinant cytosolic domains to establish structure-function relationships

    Directory of Open Access Journals (Sweden)

    Di Pietro A.

    1999-01-01

    Full Text Available Resistance to chemotherapy in cancer cells is mainly mediated by overexpression of P-glycoprotein (Pgp, a plasma membrane ATP-binding cassette (ABC transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. Pgp consists of two homologous halves each containing a transmembrane domain and a cytosolic nucleotide-binding domain (NBD which contains two consensus Walker motifs, A and B, involved in ATP binding and hydrolysis. The protein also contains an S signature characteristic of ABC transporters. The molecular mechanism of Pgp-mediated drug transport is not known. Since the transporter has an extraordinarily broad substrate specificity, its cellular function has been described as a "hydrophobic vacuum cleaner". The limited knowledge about the mechanism of Pgp, partly due to the lack of a high-resolution structure, is well reflected in the failure to efficiently inhibit its activity in cancer cells and thus to reverse multidrug resistance (MDR. In contrast to the difficulties encountered when studying the full-length Pgp, the recombinant NBDs can be obtained in large amounts as soluble proteins. The biochemical and biophysical characterization of recombinant NBDs is shown here to provide a suitable alternative route to establish structure-function relationships. NBDs were shown to bind ATP and analogues as well as potent modulators of MDR, such as hydrophobic steroids, at a region close to the ATP site. Interestingly, flavonoids also bind to NBDs with high affinity. Their binding site partly overlaps both the ATP-binding site and the steroid-interacting region. Therefore flavonoids constitute a new promising class of bifunctional modulators of Pgp.

  15. Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial.

    Science.gov (United States)

    Schmidt, Martina E; Wiskemann, Joachim; Armbrust, Petra; Schneeweiss, Andreas; Ulrich, Cornelia M; Steindorf, Karen

    2015-07-15

    Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group-based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group-based interventions. One-hundred-one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group-based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20-item multidimensional questionnaire, QoL with the EORTC QLQ-C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between-group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p-interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group-based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy. © 2014 UICC.

  16. Human colonic fibroblasts regulate stemness and chemotherapy resistance of colon cancer stem cells

    NARCIS (Netherlands)

    Colak, S.; Medema, J. P.

    2016-01-01

    There is increasing evidence that cancers are heterogeneous and contain a hierarchical organization consisting of cancer stem cells and their differentiated cell progeny. These cancer stem cells are at the core of the tumor as they represent the clonogenic cells within a tumor. Moreover, these cells

  17. Parallel Evolution under Chemotherapy Pressure in 29 Breast Cancer Cell Lines Results in Dissimilar Mechanisms of Resistance

    DEFF Research Database (Denmark)

    Tegze, Balint; Szallasi, Zoltan Imre; Haltrich, Iren

    2012-01-01

    a few parental cell lines. Methods: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7) and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross...

  18. Evaluating Metformin as a Potential Chemosensitizing Agent when Combined with Docetaxel Chemotherapy in Castration-resistant Prostate Cancer Cells.

    Science.gov (United States)

    Mayer, Michelle J; Klotz, Laurence H; Venkateswaran, Vasundara

    2017-12-01

    Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability. Wound-healing and ATP concentration assays were used to evaluate cell migration and intracellular ATP levels following metformin-docetaxel treatment. Western blotting was used for mechanistic evaluation. Metformin-docetaxel treatment significantly reduced PC3 cell viability. Metformin-docetaxel treatment did not significantly affect cell migration or intracellular ATP levels. Western blotting revealed metformin-docetaxel treatment did not significantly change AMPK or P-AMPK expression patterns. Metformin may be an effective chemosensitizer for certain types of CRPC cells, but further investigation is needed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients.

    Science.gov (United States)

    De Mattos-Arruda, Leticia; Bottai, Giulia; Nuciforo, Paolo G; Di Tommaso, Luca; Giovannetti, Elisa; Peg, Vicente; Losurdo, Agnese; Pérez-Garcia, José; Masci, Giovanna; Corsi, Fabio; Cortés, Javier; Seoane, Joan; Calin, George A; Santarpia, Libero

    2015-11-10

    Patients with primary HER2-positive breast cancer benefit from HER2-targeted therapies. Nevertheless, a significant proportion of these patients die of disease progression due to mechanisms of drug resistance. MicroRNAs (miRNAs) are emerging as critical core regulators of drug resistance that act by modulating the epithelial-to-mesenchymal transition (EMT) and cancer-related immune responses. In this study, we investigated the association between the expression of a specific subset of 14 miRNAs involved in EMT processes and immune functions and the response to neoadjuvant trastuzumab and chemotherapy in 52 patients with HER2-overexpressing breast tumors. The expression of only a single miRNA, miR-21, was significantly associated with residual disease (p = 0.030) and increased after trastuzumab-chemotherapy (p = 0.012). A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = -0.502; p = 0.005) and PDCD4 (rs = -0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. However, PTEN expression was only marginally associated with residual disease. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-κB-mediated signaling loop and activating the PI3K pathway. Our findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs.

  20. Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize metastatic castration-resistant prostate cancer cells to cabazitaxel chemotherapy.

    Science.gov (United States)

    Huang, Jinming; Jia, Jiaoyuan; Tong, Qiang; Liu, Jun; Qiu, Jun; Sun, Rong; Yao, Lixin; Yang, Chun

    2015-03-01

    Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that can stabilize some proteins by inhibiting degradation mediated by protein phosphatase 2A (PP2A), and its level in cancer is associated with resistance to chemotherapy. However, whether CIP2A could increase chemoresistance of prostate cancer (PCa) cells to chemotherapeutic agent cabazitaxel remains unclear. To determine whether CIP2A serves as a potential therapeutic target of human PCa, we utilized small interference RNA (siRNA) to knock down CIP2A expression in human PCa cells and analyzed their phenotypic changes. The data demonstrated that CIP2A was significantly elevated in mCRPC cell lines C4-2 and ARCaP(M) at both the mRNA and protein levels. CIP2A silencing led to decreased proliferation and enhanced chemosensitivity and apoptosis to cabazitaxel in human PCa cells, as well as reduced Akt phosphorylation. Our data suggesting critical roles of CIP2A in PCa cells chemoresistance to cabazitaxel and raising the possibility of CIP2A inhibition as a promising approach for chemosensitization of metastatic castration-resistant prostate cancer (mCRPC).

  1. Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Zhu, Lian-Cheng; Gao, Jian; Hu, Zhen-Hua; Schwab, Carlton L; Zhuang, Hui-Yu; Tan, Ming-Zi; Yan, Li-Mei; Liu, Juan-Juan; Zhang, Dan-Ye; Lin, Bei

    2015-01-01

    Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the roles of Lewis y antigen and the markers associated with cell-adhesion-mediated drug resistance (CAM-DR) in patients with EOC. 92 EOC patients who were treated with systemic chemotherapy after cytoreductive surgery were included in this analysis. Patients were divided into two groups, chemotherapy sensitive (n = 56) and resistant (n = 36). Immunohistochemical (IHC) staining for Lewis y and CAM-DR-related cell surface proteins including CD44, CD147, HE4 (Human epididymis protein 4), integrin α5, β1, αv and β3 were conducted on tissues collected during primary debulking surgery. Using multivariate logistic regressions, IHC results were compared to clinical variables and chemotherapy resistance to determine possible correlations. The relationships between IHC expression and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox regression analysis. Membranous expression of Lewis y and all these CAM-DR-related markers were significantly higher in the resistant group than that of the sensitive group (all P < 0.01). Multivariate regression analysis revealed that high expression of Lewis y, CD44, HE4, integrin α5 and β1 as well as advanced FIGO stage were independent risk factors for chemotherapy resistance (all P < 0.05). Advanced FIGO stage, lymph node metastasis and high expression of Lewis y, CD44, CD147, HE4, integrin α5, β1 were associated with a shorter PFS and OS (all P < 0.05). Moreover, multivariate COX analysis demonstrated that the following variates were independent predictors of worse PFS and OS survival: late FIGO stage (P = 0.013, 0.049), high expressions of Lewis y (P = 0.010, 0.036), HE4 (P

  2. A phase II trial of dasatinib in patients with metastatic castration-resistant prostate cancer treated previously with chemotherapy.

    Science.gov (United States)

    Twardowski, Przemyslaw W; Beumer, Jan H; Chen, C S; Kraft, Andrew S; Chatta, Gurkamal S; Mitsuhashi, Masato; Ye, Wei; Christner, Susan M; Lilly, Michael B

    2013-08-01

    There is a need for efficacious therapies for metastatic castration-resistant prostate cancer (mCRPC) after disease progression on docetaxel. The SRC tyrosine kinase and its related family members may be important drivers of prostate cancer and can be inhibited by dasatinib. mCRPC patients, after one previous chemotherapy, started dasatinib at 70 mg twice daily, amended to 100 mg daily. The primary endpoint was the disease control (DC) rate, defined as complete response (CR), partial response (PR), or stable disease (SD) in prostate specific antigen (PSA), RECIST, bone scan, and FACT-P score. Up to 41 patients were to be accrued (two-stage design, 21+20) to rule out a null-hypothesized effect of 5 versus 20% (α=0.05, β=0.1). Secondary endpoints included progression-free survival, toxicity, and pharmacokinetic and pharmacodynamic correlatives. Of 38 patients, 27 were evaluable for response or toxicity. The median duration of therapy was 55 days (6-284). Five patients showed DC after 8 weeks of therapy (18.5% DC, 95% CI: 6.3-38.1%). One PR (3.7% response rate, 95% CI: 0.1-19.0%) was observed in a patient treated for 284 days. Twelve patients (43%) discontinued treatment for toxicity. Dasatinib induced a decrease in phytohemagglutinin-stimulated CSF2, CD40L, GZMB, and IL-2 mRNAs in blood cells, indicating target engagement. Decreases in plasma IL-6 and bone alkaline phosphatase, and in urinary N-telopeptide, were associated with DC. Dasatinib has definite but limited activity in advanced mCRPC, and was poorly tolerated. The observation of a patient with prolonged, objective, clinically significant benefit warrants molecular profiling to select the appropriate patient population.

  3. Gd-based upconversion nanocarriers with yolk-shell structure for dual-modal imaging and enhanced chemotherapy to overcome multidrug resistance in breast cancer

    Science.gov (United States)

    Pan, Yuanwei; Zhang, Ling'e.; Zeng, Leyong; Ren, Wenzhi; Xiao, Xueshan; Zhang, Jichao; Zhang, Lili; Li, Aiguo; Lu, Guangming; Wu, Aiguo

    2015-12-01

    Multidrug resistance (MDR) of cancers is still a major challenge, and it is very important to develop visualized nanoprobes for the diagnosis and treatment of drug resistant cancers. In this work, we developed a multifunctional delivery system based on DOX-encapsulated NaYF4:Yb/Er@NaGdF4 yolk-shell nanostructures for simultaneous dual-modal imaging and enhanced chemotherapy in drug resistant breast cancer. Using the large pore volume of the nanostructure, the delivery system had a high loading efficiency and excellent stability. Also, an in vitro and in vivo toxicity study showed the good biocompatibility of the as-prepared yolk-shell nanomaterials. Moreover, by nanocarrier delivery, the uptake of DOX could be greatly increased in drug resistant MCF-7/ADR cells. Compared with free DOX, the as-prepared delivery system enhanced the chemotherapy efficacy against MCF-7/ADR cells, indicating the excellent capability for overcoming MDR. Furthermore, core-shell NaYF4:Yb/Er@NaGdF4 improved the upconversion luminescence (UCL) performance, and the designed delivery system could also be applied for simultaneous UCL and magnetic resonance (MR) imaging, which could be a good candidate as a dual-modal imaging nanoprobe. Therefore, we developed a multifunctional yolk-shell delivery system, which could have potential applications as a visualized theranostic nanoprobe to overcome MDR in breast cancer.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. E-Cadherin As A Chemotherapy Resistance Mechanism On Metastatic Breast Cancer

    Science.gov (United States)

    2011-05-01

    cell adhesion to E-, P-, and L- selectin: role of mucin-type glycoproteins. Cancer Res 1995; 55 (19): 4425-31. 12. Paschos KA, Canovas D, Bird NC. The...promoter or the result of global hypomethylation. The H19 gene is a paternally imprinted gene whose methylation is modulated during gametogenesis...hepatocytes. Importantly, this loss of methylation was at least semi-specific and not global as the imprinted H19 gene remained methylated. The

  6. Chemotherapy for Oral Cancer.

    Science.gov (United States)

    Hartner, Lee

    2018-01-01

    The use of chemotherapy, including immunotherapy, in oral squamous cell carcinoma has expanded considerably in the past several years. Its use mirrors that in the treatment of squamous cell carcinoma affecting other structures in the head and neck. This article summarizes the current evidence that guides use of chemotherapy both in combination with radiation and as monotherapy for patients with advanced disease. It also addresses the expanding role of immunotherapy, particularly use of programmed cell death-ligand 1 inhibitors, in the treatment of advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. ANTIPSYCHOTICS REVERSE P-GLYCOPROTEIN-MEDIATED DOXORUBICIN RESISTANCE IN HUMAN UTERINE SARCOMA MES-SA/Dx5 CELLS: A NOVEL APPROACH TO CANCER CHEMOTHERAPY.

    Science.gov (United States)

    Angelini, A; Ciofani, G; Conti, P

    2015-01-01

    Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp (100-fold), were treated with the antipsychotic alone (1, 10 and 20 μM) or in combination with different concentrations of doxo (2, 4 and 8 μM). The accumulation and cytotoxicity of doxo (MTT assay) and cellular GSH content (GSH assay) in comparison with verapamil, a well-known Pgp inhibitor, used as reference molecule were examined. It was found that the three compounds significantly enhanced the intracellular accumulation of doxo in resistant cancer cells, when compared with cells receiving doxo alone (p 30%) in resistant cells, when compared to untreated control cells (ptheobromine showed to be an effective Pgp inhibitor with the lowest toxicity.

  8. Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Angelergues, Antoine; Maillet, Denis; Fléchon, Aude; Ozgüroglu, Mustafa; Mercier, Florence; Guillot, Aline; Le Moulec, Sylvestre; Gravis, Gwenaelle; Beuzeboc, Philippe; Massard, Christophe; Fizazi, Karim; de La Motte Rouge, Thibault; Delanoy, Nicolas; Elaidi, Reza-Thierry; Oudard, Stéphane

    2014-06-01

    A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival. Multicentre retrospective review of consecutive patients treated with cabazitaxel second-line chemotherapy for mCRPC. Collection of baseline characteristics, disease history and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and radiological/clinical progression-free survival (PFS) for patient groups corresponding to different definitions of PSA flare estimated by the Kaplan-Meier method and compared using the log-rank test. Overall, 125 patients were included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare lasted <2.6 months. A PSA flare followed by a ⩾ 50% decrease was associated with a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for a ⩾ 30% rather than ⩾ 5 0% decrease were 10.4 and 16.5 months. These outcomes were not significantly different from those in patients with immediate PSA decreases of ⩾ 50% or ⩾ 30% from baseline, but were significantly better than in patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for OS). The PSA response to cabazitaxel, with or without initial flare, was associated with a strong survival benefit. The taxane-induced flare during the first 12 weeks of therapy can be ignored when evaluating PSA response. Copyright © 2014. Published by Elsevier Ltd.

  9. The Prognostic Value of Plasma YKL-40 in Patients With Chemotherapy-Resistant Ovarian Cancer Treated With Bevacizumab

    DEFF Research Database (Denmark)

    Boisen, Mogens K; Madsen, Christine V; Dehlendorff, Christian

    2016-01-01

    OBJECTIVE: YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patient...... treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab.......OBJECTIVE: YKL-40 is a proangiogenic glycoprotein that is secreted by cancer cells and inflammatory cells. The expression of YKL-40 is induced by vascular endothelial growth factor inhibition. We tested the hypothesis that low baseline plasma YKL-40 is associated with improved outcomes in patients...... with ovarian cancer treated with bevacizumab. METHODS: One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during...

  10. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    National Research Council Canada - National Science Library

    Huang, Chung-Yung

    2006-01-01

    .... Further, current clinical, pathological and molecular markers poorly predict the response and resistance of chemotherapy, and the molecular mechanisms of chemotherapy resistance are largely unknown...

  11. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    National Research Council Canada - National Science Library

    Huang, Chung-Ying

    2007-01-01

    .... Further current clinical pathological and molecular markers poorly predict the response and resistance of chemotherapy and the molecular mechanisms of chemotherapy resistance are largely unknown...

  12. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas...... skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P

  13. Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.

    Science.gov (United States)

    Teillant, Aude; Gandra, Sumanth; Barter, Devra; Morgan, Daniel J; Laxminarayan, Ramanan

    2015-12-01

    The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120,000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40,000 for a 10% reduction in efficacy to 280,000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15,000 for a 70% reduction). We estimated that every year, 13,120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. Increasing antibiotic

  14. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer.

    Science.gov (United States)

    Kanai, Masashi; Yoshimura, Kenichi; Asada, Masanori; Imaizumi, Atsushi; Suzuki, Chihiro; Matsumoto, Shigemi; Nishimura, Takafumi; Mori, Yukiko; Masui, Toshihiko; Kawaguchi, Yoshiya; Yanagihara, Kazuhiro; Yazumi, Shujiro; Chiba, Tsutomu; Guha, Sushovan; Aggarwal, Bharat B

    2011-07-01

    Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy. Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study. Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested. Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.

  15. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients with advanced urothelial cancer. A panel of international experts has formulated grade A through D recommendations for the management......To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...... the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed...

  16. Abiraterone in metastatic prostate cancer without previous chemotherapy

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Bono, J. De; Molina, A.; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; Carles, J.; Mulders, P.F.A.; Basch, E.; Small, E.J.; Saad, F.; Schrijvers, D.; Poppel, H. van; Mukherjee, S.D.; Suttmann, H.; Gerritsen, W.R.; Flaig, T.W.; George, D.J.; Yu, E.Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C.S.; Taplin, M.E.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H.I.; Rathkopf, D.E.

    2013-01-01

    BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we

  17. Development of a Nomogram for Predicting Severe Neutropenia Associated With Docetaxel-Based Chemotherapy in Patients With Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Hirasawa, Yosuke; Nakashima, Jun; Sugihara, Toru; Takizawa, Issei; Gondo, Tatsuo; Nakagami, Yoshihiro; Horiguchi, Yutaka; Ohno, Yoshio; Namiki, Kazunori; Ohori, Makoto; Tachibana, Masaaki

    2017-02-01

    Neutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. Sixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. Age and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Graff, J N; Baciarello, G; Armstrong, A J

    2016-01-01

    BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years...... who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PATIENTS AND METHODS: PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration......-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged patients (35%) who...

  19. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  20. Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo.

    Science.gov (United States)

    Taplin, Mary-Ellen; Armstrong, Andrew J; Lin, Ping; Krivoshik, Andrew; Phung, De; Parli, Teresa; Tombal, Bertrand; Beer, Tomasz M

    2017-12-01

    Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Of 1,717 patients enrolled in PREVAIL 242 (14.1%) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95% CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95% CI 0.06-0.51 and low volume disease HR 0.25, 95% CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Chemotherapy naïve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients. Copyright © 2017 American Urological Association

  1. Serum alkaline phosphatase differentiates prostate-specific antigen flare from early disease progression after docetaxel chemotherapy in castration-resistant prostate cancer with bone metastasis.

    Science.gov (United States)

    Han, Kyung Seok; Hong, Sung Joon

    2014-10-01

    A transient rise in prostate-specific antigen (PSA) after the initiation of chemotherapy, called as PSA flare, has been frequently reported in patients with castration-resistant prostate cancer (CRPC) but there has been no way to differentiate PSA rises in CRPC. We investigated whether bone-related serum markers differentiate PSA flare from progression in CRPC patients with bone metastasis. We reviewed CRPC patients with bone metastasis who received systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP), calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow-up serum parameters after the first cycle of chemotherapy were included in statistical analyses. PSA increased in 38 patients (45.8 %) at the first evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or did not decrease to the stabilization level by the third evaluation in 22 (26.5 %) patients, while PSA decreased to the stabilization or response level by the third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The univariate analyses showed that no baseline parameters were associated with PSA flare, but the initial ALP decrease, changed ALP ratio, and median calcium level were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012, respectively). Multivariate logistic regression analysis showed that a change in the ALP level is an independent predictive factor for PSA flare (p = 0.017). ALP is a useful biomarker to differentiate PSA flare from early PSA progression during docetaxel chemotherapy in CRPC patients with bone metastasis.

  2. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  3. Low drug resistance to both platinum and taxane chemotherapy on an in vitro drug resistance assay predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer.

    Science.gov (United States)

    Matsuo, Koji; Bond, Virginia K; Eno, Michele L; Im, Dwight D; Rosenshein, Neil B

    2009-12-01

    The objective of this study was to evaluate the role of an in vitro drug resistance assay to platinum and taxane in the management of advanced epithelial ovarian, fallopian and primary peritoneal cancer. All patients with FIGO Stage IIIc and IV who received postoperative chemotherapy with platinum and taxane for more than 4 courses after the initial cytoreductive surgery between 1995 and 2008 were evaluated. Patients who received neoadjuvant chemotherapy were not included. An in vitro drug resistance assay (EDR Assay, Oncotech, Tustin, CA) was used to determine drug resistance for each patient's tumor tissue. Level of drug resistance was described as extreme (EDR), intermediate (IDR), or low (LDR). Response to chemotherapy and survival were correlated to the EDR Assay. Of the 335 patients who underwent primary cytoreductive surgery, 173 cases met the criteria for statistical evaluation. The 58 patients (33.5%) whose tumors had LDR to both platinum and taxane had statistically improved progression-free survival and overall survival (OS) compared with the 115 patients (66.5%) who demonstrated IDR or EDR to platinum and/or taxane (5-year OS rates, 41.1% vs. 30.9%, p = 0.014). The 5-year OS rates for the 28 (16.2%) cases that had optimal cytoreduction with LDR to both platinum and taxane was significantly improved over the 62 (35.8%) cases that were suboptimally cytoreduced with IDR or EDR to platinum and/or taxane (54.1% vs. 20.4%, respectively, p chemotherapy, as determined by an in vitro drug resistance assay, independently predicts improved survival in patients with advanced epithelial ovarian, fallopian and peritoneal cancer, especially in those patients who undergo optimal primary cytoreduction.

  4. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    Science.gov (United States)

    Satoh, Takefumi; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a ≥50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. Results Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by ≥1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (>20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. Conclusions Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical

  5. Chemotherapy for advanced gastric cancer.

    Science.gov (United States)

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

  6. A Phase 2 Trial of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer and without Prior Chemotherapy (JPN-201 Study)

    Science.gov (United States)

    Matsubara, Nobuaki; Uemura, Hirotsugu; Satoh, Takefumi; Suzuki, Hiroyoshi; Nishiyama, Tsutomu; Uemura, Hiroji; Hashine, Katsuyoshi; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. Results A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: −66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2. Conclusions Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate

  7. Clostridium Perfringens Enterotoxin C-terminal domain labeled to fluorescent Dyes for in vivo visualization of micro-metastatic chemotherapy-resistant ovarian cancer

    Science.gov (United States)

    Cocco, Emiliano; Shapiro, Erik M.; Gasparrini, Sara; Lopez, Salvatore; Schwab, Carlton L.; Bellone, Stefania; Bortolomai, Ileana; Sumi, Natalia J.; Bonazzoli, Elena; Nicoletti, Roberta; Deng, Yang; Saltzman, W. Mark; Zeiss, Caroline J.; Centritto, Floriana; Black, Jonathan D.; Silasi, Dan-Arin; Ratner, Elena; Azodi, Masoud; Rutherford, Thomas J.; Schwartz, Peter E.; Pecorelli, Sergio; Santin, Alessandro D.

    2015-01-01

    Identification of micro-metastatic disease at the time of surgery remains extremely challenging in ovarian cancer patients. We used fluorescence microscopy, an in vivo imaging system and a fluorescence stereo microscope to evaluate fluorescence distribution in claudin-3 and -4 overexpressing ovarian tumors, floating tumor clumps isolated from ascites and healthy organs. To do so, mice harboring chemotherapy-naïve and chemotherapy-resistant human ovarian cancer xenografts or patient-derived xenografts (PDX) were treated with the carboxi-terminal binding domain of the Clostridium Perfringens Enterotoxin (c-CPE) conjugated to FITC (FITC-c-CPE) or the near-infrared (NIR) fluorescent tag IRDye CW800 (CW800-c-CPE) either intraperitoneal (IP) or intravenous (IV). We found tumor fluorescence to plateau at 30 minutes after IP injection of both the FITC-c-CPE and the CW800-c-CPE peptides and to be significantly higher than in healthy organs (p<0.01). After IV injection of CW800-c-CPE, tumor fluorescence plateaued at 6 hours while the most favorable tumor to background fluorescence ratio (TBR) was found at 48 hours in both mouse models. Importantly, fluorescent c-CPE was highly sensitive for the in vivo visualization of peritoneal micro-metastatic tumor implants and the identification of ovarian tumor spheroids floating in malignant ascites that were otherwise not detectable by conventional visual observation. The use of the fluorescent c-CPE peptide may represent a novel and effective optical approach at the time of primary debulking surgery for the real-time detection of micro-metastatic ovarian disease overexpressing the claudin-3 and -4 receptors or the identification of residual disease at the time of interval debulking surgery after neoadjuvant chemotherapy treatment. PMID:26060989

  8. Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: molecular mechanisms unveiled by gene expression profiling.

    Science.gov (United States)

    Koch, Martin; Krieger, Michaela L; Stölting, Daniel; Brenner, Norbert; Beier, Manfred; Jaehde, Ulrich; Wiese, Michael; Royer, Hans-Dieter; Bendas, Gerd

    2013-04-15

    Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17). Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells. This suggests that the mode of action of liposomal CDDP is different from the free drug. To gain insight into mechanisms of liposomal CDDP activity, we performed a transcriptome analysis of untreated A2780cis cells, and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP. A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug. p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP. The free drug induced expression of essential genes of the intrinsic (mitochondrial) apoptosis pathway (BAX, BID, CASP9) most likely through p38MAPK activation. In contrast, liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis (TNFRSF10B-DR5, CD70-TNFSF7). It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway. Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array. This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

    Science.gov (United States)

    Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

    2016-01-01

    There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

  10. Progressive Resistance Training and Cancer Testis (PROTRACT - Efficacy of resistance training on muscle function, morphology and inflammatory profile in testicular cancer patients undergoing chemotherapy: design of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mackey Abigail L

    2011-08-01

    Full Text Available Abstract Background Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP. This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT. Design/Methods The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR initiated at the onset of treatment, or to standard care (UNT. 15 healthy matched control subjects (CON will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. Primary outcome: mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. Secondary outcomes: maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers

  11. Progressive resistance training and cancer testis (PROTRACT) - efficacy of resistance training on muscle function, morphology and inflammatory profile in testicular cancer patients undergoing chemotherapy: design of a randomized controlled trial.

    Science.gov (United States)

    Christensen, Jesper F; Andersen, Jesper L; Adamsen, Lis; Lindegaard, Birgitte; Mackey, Abigail L; Nielsen, Rie H; Rørth, Mikael; Daugaard, Gedske

    2011-08-01

    Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT). The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR) initiated at the onset of treatment, or to standard care (UNT). 15 healthy matched control subjects (CON) will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks) including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers, lipid and glucose metabolism in blood samples. Health related Quality of Life (Qo

  12. Predictors of Chemotherapy-Induced Toxicity and Treatment Outcomes in Elderly Versus Younger Patients With Metastatic Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette

    2016-01-01

    used to evaluate treatment-related toxicity and efficacy. Logistic and Cox regression models were used to predict toxicity and survival. RESULTS: Age ≥ 75 years (odds ratio [OR], 2.33), baseline levels of hemoglobin (OR, 0.89), and previous metastatic epidural spinal cord compression (MESCC; OR, 1......BACKGROUND: In the present study, we examined possible predictors of chemotherapy-induced toxicity, treatment outcomes, and the consequences of dose reductions in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving standard docetaxel. PATIENTS AND METHODS: Medical.......70) were predictive of grade 3 and 4 nonhematologic toxicity. Previous MESCC was associated with a greater risk of febrile neutropenia (OR, 2.74). The median progression-free survival (PFS) and overall survival (OS) were 6.4 and 15.4 months, respectively. Survival was similar in the older (age ≥ 75 years...

  13. Chemotherapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Chemotherapy and You: Support for People With Cancer Chemotherapy ... ePub This booklet covers: Questions and answers about chemotherapy. Answers common questions, such as what chemotherapy is ...

  14. Prostate-Specific Antigen Changes As Surrogate for Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Second-Line Chemotherapy

    Science.gov (United States)

    Halabi, Susan; Armstrong, Andrew J.; Sartor, Oliver; de Bono, Johann; Kaplan, Ellen; Lin, Chen-Yen; Solomon, Nicole C.; Small, Eric J.

    2013-01-01

    Purpose Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy. Patients and Methods Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy. Results The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes. PMID:24101043

  15. A randomized cross-over trial to detect differences in arm volume after low- and heavy-load resistance exercise among patients receiving adjuvant chemotherapy for breast cancer at risk for arm lymphedema

    DEFF Research Database (Denmark)

    Bloomquist, Kira; Hayes, Sandi; Adamsen, Lis

    2016-01-01

    BACKGROUND: In an effort to reduce the risk of breast cancer-related arm lymphedema, patients are commonly advised to avoid heavy lifting, impacting activities of daily living and resistance exercise prescription. This advice lacks evidence, with no prospective studies investigating arm volume...... changes after resistance exercise with heavy loads in this population. The purpose of this study is to determine acute changes in arm volume after a session of low- and heavy-load resistance exercise among women undergoing adjuvant chemotherapy for breast cancer at risk for arm lymphedema. METHODS....../DESIGN: This is a randomized cross-over trial. PARTICIPANTS: Women receiving adjuvant chemotherapy for breast cancer who have undergone axillary lymph node dissection will be recruited from rehabilitation centers in the Copenhagen area. INTERVENTION: Participants will be randomly assigned to engage in a low- (two sets of 15...

  16. Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.

    Science.gov (United States)

    Mijwel, Sara; Backman, Malin; Bolam, Kate A; Olofsson, Emil; Norrbom, Jessica; Bergh, Jonas; Sundberg, Carl Johan; Wengström, Yvonne; Rundqvist, Helene

    2018-01-18

    Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC. cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold. Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30). Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high

  17. Salvage chemotherapy in recurrent platinum-resistant or refractory epithelial ovarian cancer with Carboplatin and distearoylphosphatidylcholine pegylated liposomal Doxorubicin (lipo-dox®).

    Science.gov (United States)

    Khemapech, Nipon; Oranratanaphan, S; Termrungruanglert, W; Lertkhachonsuk, R; Vasurattana, A

    2013-01-01

    To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

  18. Prostate-Specific Antigen Flare Phenomenon Induced by Abiraterone Acetate in Chemotherapy-Naive Patients With Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Ueda, Yujiro; Matsubara, Nobuaki; Tabata, Ken-Ichi; Satoh, Takefumi; Kamiya, Naoto; Suzuki, Hiroyoshi; Kawahara, Takashi; Uemura, Hiroji

    2017-04-01

    Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist and chemotherapy. However, its incidence and the significance for the clinical outcomes of patients treated with abiraterone acetate (AA) are uncertain. A multicenter retrospective analysis of chemotherapy-naive patients treated with AA for metastatic castration-resistant prostate cancer (mCRPC) was conducted. The baseline characteristics, treatment history of mCRPC, and serum PSA kinetics during AA treatment were collected. The log-rank test was applied to compare progression-free survival (PFS) between patient groups with a PSA flare according to the different definitions and immediate PSA declines. The data from 83 patients were analyzed. An immediate PSA decline of any amount was observed in 59 patients (71.1%). According to the various definitions of PSA flare, its incidence ranged from 6.0% to 10.8%. Although the median interval to the peak PSA level was 0.95 month, regardless of the PSA flare definition, the interval to the PSA nadir showed a wide range of 2.8 to 7.6 months. In PSA flare subgroup, the median PFS in patients with any PSA decline to less than the baseline and > 30% decline from the baseline was 12.4 months. The PFS duration of PSA flare patients did not significantly differ from that of patients with an immediate PSA decline of any amount and immediate > 30% decline without PSA flare. The PSA flare phenomenon is not rare event during AA treatment. A PSA decline during AA treatment, with or without a PSA flare, was associated with favorable clinical outcomes. Thus, AA should not be withdrawn early in patients with mCRPC in whom an initial, isolated PSA increase has been observed. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The coordinated role of CYP450 enzymes and P-gp in determining cancer resistance to chemotherapy.

    Science.gov (United States)

    Azzariti, Amalia; Porcelli, Letizia; Quatrale, Anna Elisa; Silvestris, Nicola; Paradiso, Angelo

    2011-10-01

    The relationship between CYP450 and P-gp occurs at different levels. It is known that certain substrates of P-gp undergo metabolic transformations by various CYP450 isoforms; in addition some of them demonstrated to be activators of both P-gp and CYP450. The majority of such compounds are well-known chemotherapeutics, therefore the purpose of this review is to clarify whether there is a relationship between the simultaneous modulation of CYP450 and P-gp and the onset of drug resistance in tumors treatment. Here, we discuss the biological aspects of the topic in relation to the various tissues distribution of CYP450 and P-gp, the recent findings regarding the ability of some chemotherapeutics in modulating both P-gp and CYP450, whether this modulation is ultimately responsible for the onset of drug resistance in cancer treatment and the promising role of gene polymorphisms in determining the interindividual variability in drug responses in clinical practice.

  20. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo.

    Science.gov (United States)

    English, Diana P; Bellone, Stefania; Schwab, Carlton L; Roque, Dana M; Lopez, Salvatore; Bortolomai, Ileana; Cocco, Emiliano; Bonazzoli, Elena; Chatterjee, Sudeshna; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2015-02-01

    Solitomab is a novel, bispecific, single-chain antibody that targets epithelial cell adhesion molecule (EpCAM) on tumor cells and also contains a cluster of differentiation 3 (CD3) (T-cell coreceptor) binding region. The authors evaluated the in vitro activity of solitomab against primary chemotherapy-resistant epithelial ovarian carcinoma cell lines as well as malignant cells in ascites. EpCAM expression was evaluated by flow cytometry in 5 primary ovarian cancer cell lines and in 42 fresh ovarian tumor cell cultures in ascites from patients with mainly advanced or recurrent, chemotherapy-resistant disease. The potential activity of solitomab against EpCAM-positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release, cell-mediated cytotoxicity assays. EpCAM expression was detected by flow cytometry in approximately 80% of the fresh ovarian tumors and primary ovarian tumor cell lines tested. EpCAM-positive, chemotherapy-resistant cell lines were identified as resistant to natural killer cell-mediated or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean±standard error of the mean, 3.6%±0.7% of cells killed after incubation of EpCAM-positive cell lines with control bispecific antibody). In contrast, after incubation with solitomab, EpCAM-positive, chemotherapy-resistant cells became highly sensitive to T-cell cytotoxicity (mean±standard error of the mean, 28.2%±2.05% of cells killed; Ptreatment of chemotherapy-resistant ovarian cancers that overexpress EpCAM. © 2014 American Cancer Society.

  1. Enhancement of ovarian cancer chemotherapy by delivery of multidrug-resistance gene small interfering RNA using tumor targeting Salmonella.

    Science.gov (United States)

    Deng, Jiaqi; Guo, Yi; Jiang, Zhongmin; Yang, Min; Li, Huaifang; Wang, Jianjun

    2015-04-01

    The aim of this study was to observe the effect of attenuated Salmonella typhi as a tumor-targeting delivery vector for multidrug-resistance gene (MDR1) small interfering RNA (siRNA). The cisplatin (DDP)-resistant ovarian cancer cell line SKOV-3/DDP was established by treatment with gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed into attenuated Salmonella typhi strain  SL7207. SKOV-3/DDP cells were incubated with recombinant Salmonella and then subjected to analysis of MDR1 expression by real-time polymerase chain reaction and Western blot. SKOV-3/DDP tumor-bearing mice were established by subcutaneously injecting BALB/c nude mice with SKOV-3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor growth and mouse survival were observed. Compared with parental cell line, the DDP-resistant SKOV-3/DDP cells expressed a much higher level of MDR1. The expression of MDR1 in SKOV-3/DDP cells infected with the Salmonella strain bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP tolerance of these cells was reversed. Tumor-bearing nude mice that were orally receiving recombinant Salmonella experienced a slow tumor growth and became more sensitive to DDP. Attenuated Salmonella typhi may represent a promising vector for in vivo administration of RNA interference therapy against malignant tumors. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  2. Cancer chemotherapy and biotherapy: principles and practice

    National Research Council Canada - National Science Library

    Chabner, Bruce; Longo, Dan L

    2011-01-01

    "Updated to include the newest drugs and those currently in development, Cancer Chemotherapy and Biotherapy, Fifth Edition is a comprehensive reference on the preclinical and clinical pharmacology of anticancer agents...

  3. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... mutational status received three cycles of capecitabine 2000 mg/m(2) days 1-14 q3w and oxaliplatin 130 mg iv day 1 q3w. Wild-type patients received the same chemotherapy supplemented with panitumumab 9 mg/kg iv q3w. After the operation, patients fulfilling the international criteria for adjuvant chemotherapy......, i.e. high-risk stage II and III patients, received five cycles of the same chemotherapy without panitumumab. Patients not fulfilling the criteria were offered follow-up only. The primary endpoint was the fraction of patients not fulfilling the criteria for adjuvant chemotherapy (converted patients...

  4. Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

    Science.gov (United States)

    de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

    2017-04-01

    Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced

  5. Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

    Science.gov (United States)

    Bloomfield, D J; Krahn, M D; Neogi, T; Panzarella, T; Smith, T J; Warde, P; Willan, A R; Ernst, S; Moore, M J; Neville, A; Tannock, I F

    1998-06-01

    To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). A treatment that reduces symptoms and improves quality of life has the potential to reduce

  6. Efflux Pump‑Mediated Resistance in Chemotherapy

    African Journals Online (AJOL)

    The problem of resistance to chemotherapeutic agents is perhaps one of the greatest challenges in clinical medicine. Drug resistance in malaria, Human Immunodeficiency Virus. (HIV)/Acquired Immune Deficiency Syndrome (AIDS), bacterial infections, and cancer has continued to challenge the ingenuity of ...

  7. Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response

    NARCIS (Netherlands)

    Lips, Esther H; Michaut, Magali; Hoogstraat, Marlous; Mulder, Lennart; Besselink, Nicolle J M; Koudijs, Marco J; Cuppen, Edwin; Voest, Emile E; Bernards, Rene; Nederlof, Petra M; Wesseling, Jelle; Rodenhuis, Sjoerd; Wessels, Lodewyk F A

    2015-01-01

    INTRODUCTION: In triple negative breast cancers (TNBC) the initial response to chemotherapy is often favorable, but relapse and chemotherapy resistance frequently occur in advanced disease. Hence there is an urgent need for targeted treatments in this breast cancer subtype. In the current study we

  8. Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression.

    Science.gov (United States)

    Cai, Liqiong; Wang, Zehua; Liu, Denghua

    2016-05-01

    Cervical cancer is one of the most common female malignancies in the world, and chemotherapeutic drug resistance is a major obstacle to cancer therapy. Enhancer of zeste homolog 2 (EZH2) is an enzymatic subunit of polycomb repressive complex 2 (PRC2) and catalyzes the repressive histone H3 lysine 27 trimethylation (H3K27me3). However, the role of EZH2 on the chemotherapy drug resistance in cervical cancers remains unclear. In the present study, the cervical carcinoma specimens and paired normal tissue specimens were obtained and the expression of EZH2 was detected by western blotting. The results showed that high levels of EZH2 were detected in cervical carcinoma tissues, compared with paired control tissues (**p EZH2 were designed and used to interfere with endogenous EZH2 expression. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays following treatment with various concentrations of cisplatin in HeLa and HeLa/DDP cells. The MTT assay results showed that knockdown of EZH2 in HeLa/DDP cells caused a 2.29- or 1.83-fold decrease in the cisplatin IC50 values (for shRNA1-EZH2, 34.88 vs. 15.21 μg/mL; p EZH2, 34.88 vs. 19.09 μg/mL; p EZH2 activity was also suppressed by 3-deazaneplanocin A (DZNep), EZH2 inhibitor, and the results demonstrated that, meanwhile, DZNep potently inhibited cell viability of HeLa/DDP cells, partly by suppression the levels of EZH2 and H3K27me3, but not H3K27me2, which was detected by western blotting analysis. Moreover, cell migration assay results showed that knockdown of EZH2 decreased cell metastasis of cervical cancer cells. Furthermore, cell cycle was detected by fluorescence-activated cell sorting (FACS) assay and the results demonstrated that interference with EZH2 expression increased the percentage of cells at G0/G1 phase and the HeLa/DDP cells were blocked at G0/G1 phase. Interestingly, western blotting results revealed that higher expression of EZH2 was related with

  9. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302).

    Science.gov (United States)

    Rathkopf, Dana E; Smith, Matthew R; de Bono, Johann S; Logothetis, Christopher J; Shore, Neal D; de Souza, Paul; Fizazi, Karim; Mulders, Peter F A; Mainwaring, Paul; Hainsworth, John D; Beer, Tomasz M; North, Scott; Fradet, Yves; Van Poppel, Hendrik; Carles, Joan; Flaig, Thomas W; Efstathiou, Eleni; Yu, Evan Y; Higano, Celestia S; Taplin, Mary-Ellen; Griffin, Thomas W; Todd, Mary B; Yu, Margaret K; Park, Youn C; Kheoh, Thian; Small, Eric J; Scher, Howard I; Molina, Arturo; Ryan, Charles J; Saad, Fred

    2014-11-01

    Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy. Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302. Study COU-AA-302, a double-blind placebo-controlled study, enrolled patients with mCRPC from April 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1). Patients were randomised 1:1 to abiraterone 1000mg plus prednisone 5mg twice daily by mouth versus prednisone. Co-primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O'Brien-Fleming Lan-DeMets α-spending function was used for OS. Adverse events were summarised descriptively. With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45-0.61]; ppatient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports. The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for ≥24 mo. Study COU-AA-302, ClinicalTrials.gov number, NCT00887198. The updated results of this ongoing study

  10. Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer

    Science.gov (United States)

    Rodriguez-Aguayo, Cristian; Monroig, Paloma del C; Redis, Roxana S; Bayraktar, Emine; Almeida, Maria I; Ivan, Cristina; Fuentes-Mattei, Enrique; Rashed, Mohammed H; Chavez-Reyes, Arturo; Ozpolat, Bulent; Mitra, Rahul; Sood, Anil K; Calin, George A; Lopez-Berestein, Gabriel

    2017-01-01

    The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene. The inhibition of miR-25-3p and miR-15a-5p decreased the proliferation, motility, invasiveness and angiogenic potential and increased apoptosis when combined with docetaxel. Alteration of this regulatory circuit causes poor overall survival outcome in ovarian cancer patients. These results highlight miR-15a-5p and miR-25-3p as key regulators of miR-18a-3p expression and its downstream target K-RAS, through direct modulation of hnRNPA1 expression. Our results demonstrate the therapeutic potential of inhibiting miR-25-3p and miR-15a-5p and the use of miR-18a-3p/KRAS ratio as a prominent outcome prognostic factor. PMID:28904816

  11. Regulation of hnRNPA1 by microRNAs controls the miR-18a-K-RAS axis in chemotherapy-resistant ovarian cancer.

    Science.gov (United States)

    Rodriguez-Aguayo, Cristian; Monroig, Paloma Del C; Redis, Roxana S; Bayraktar, Emine; Almeida, Maria I; Ivan, Cristina; Fuentes-Mattei, Enrique; Rashed, Mohammed H; Chavez-Reyes, Arturo; Ozpolat, Bulent; Mitra, Rahul; Sood, Anil K; Calin, George A; Lopez-Berestein, Gabriel

    2017-01-01

    The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene. The inhibition of miR-25-3p and miR-15a-5p decreased the proliferation, motility, invasiveness and angiogenic potential and increased apoptosis when combined with docetaxel. Alteration of this regulatory circuit causes poor overall survival outcome in ovarian cancer patients. These results highlight miR-15a-5p and miR-25-3p as key regulators of miR-18a-3p expression and its downstream target K-RAS, through direct modulation of hnRNPA1 expression. Our results demonstrate the therapeutic potential of inhibiting miR-25-3p and miR-15a-5p and the use of miR-18a-3p/KRAS ratio as a prominent outcome prognostic factor.

  12. Nano carriers that enable co-delivery of chemotherapy and RNAi agents for treatment of drug-resistant cancers.

    Science.gov (United States)

    Tsouris, Vasilios; Joo, Min Kyung; Kim, Sun Hwa; Kwon, Ick Chan; Won, You-Yeon

    2014-01-01

    Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of chemotherapeutic treatments. The drug resistance has a genetic basis that is caused by an abnormal gene expression. There are several types of drug resistance: efflux pumps reducing the cellular concentration of the drug, alterations in membrane lipids that reduce cellular uptake, increased or altered drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair of the damaged DNA, and alteration of the cell cycle checkpoints (Gottesman et al., 2002; Holohan et al., 2013). siRNA is used to silence the drug resistant phenotype and prevent this drug resistance response. Of the listed types of drug resistance, pump-type resistance (e.g., high expression of ATP-binding cassette transporter proteins such as P-glycoproteins (Pgp; also known as multi-drug resistance protein 1 or MDR1, encoded by the ATP-Binding Cassette Sub-Family B Member 1 (ABCB1) gene)) and apoptosis inhibition (e.g., expression of anti-apoptotic proteins such as Bcl-2) are the most frequently targeted for gene silencing. The co-delivery of siRNA and chemotherapeutic drugs has a synergistic effect, but many of the current projects do not control the drug release from the nanocarrier. This means that the drug payload is released before the drug resistance proteins have degraded and the drug resistance phenotype has been silenced. Current research focuses on cross-linking the carrier's polymers to prevent premature drug release, but these carriers still rely on environmental cues to release the drug payload, and the drug may be released too early. In this review, we studied the release kinetics of siRNA and chemotherapeutic drugs from a broad range of carriers. We also give examples of carriers used to co-deliver siRNA and drugs to drug-resistant tumor cells, and we examine how modifications to the carrier affect the delivery. Lastly, we give our recommendations for the future directions of the co-delivery of si

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

    Directory of Open Access Journals (Sweden)

    Sidra Naveed

    2014-11-01

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

  14. Weight changes during chemotherapy for breast cancer

    Directory of Open Access Journals (Sweden)

    Luciano José Megale Costa

    Full Text Available CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8, adjuvant (n = 74 or palliative (n = 24 chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patients’ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42% (p = 0.21 of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001. In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 % (p < 0.00001 per month, whereas in the metastatic (palliative group, we observed a mean loss of 0.52 ± 1.21% (p = 0.11 of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy.

  15. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.

    2014-01-01

    of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference...... and TNF-α (all P cytokine concentrations were comparable with the pretreatment levels in both GCC-groups but remained elevated compared with REF (P ...). Changes in TNF-α correlated with pulmonary toxicity (P markers compared with healthy...

  16. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  17. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

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

  18. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients

  19. Metastatic urachal cancer responding to FOLFOX chemotherapy.

    Science.gov (United States)

    Tran, Ben; McKendrick, Joe

    2010-04-01

    Metastatic urachal cancer is a rare disease and subsequently, does not have a defined systemic treatment. Although urachal cancer is most commonly adenocarcinoma and histologically similar to colon cancer, treatment selection is usually based upon location (the proximity of the urachus to the bladder) with bladder cancer regimens the most commonly prescribed. We report a case of metastatic urachal cancer where the immunohistochemical profile's similarities to colon cancer led to treatment with colon cancer specific chemotherapy. Our case is the first to report urachal cancer treated with and responding to modified FOLFOX6. In the age of targeted therapy, where molecular biology drives treatment selection, our case highlights that in rare tumors, when evidence is often lacking, a common sense approach can often prevail.

  20. Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

    Science.gov (United States)

    Stenner, Frank; Rothschild, Sacha I; Betticher, Daniel; Caspar, Clemens; Morant, Rudolf; Popescu, Razvan; Rauch, Daniel; Huber, Urs; Zenhäusern, Reinhard; Rentsch, Cyrill; Cathomas, Richard

    2017-08-24

    The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Doxorubicin-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers for NIR-triggered photodynamic therapy and enhanced chemotherapy in drug-resistant breast cancers.

    Science.gov (United States)

    Zeng, Leyong; Pan, Yuanwei; Tian, Ying; Wang, Xin; Ren, Wenzhi; Wang, Shouju; Lu, Guangming; Wu, Aiguo

    2015-07-01

    The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm-TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

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

    2014-01-01

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

  3. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  4. Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches

    NARCIS (Netherlands)

    Wijngaarden, Johannes Willem van

    2011-01-01

    One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches

  5. Abiraterone in metastatic prostate cancer without previous chemotherapy.

    Science.gov (United States)

    Ryan, Charles J; Smith, Matthew R; de Bono, Johann S; Molina, Arturo; Logothetis, Christopher J; de Souza, Paul; Fizazi, Karim; Mainwaring, Paul; Piulats, Josep M; Ng, Siobhan; Carles, Joan; Mulders, Peter F A; Basch, Ethan; Small, Eric J; Saad, Fred; Schrijvers, Dirk; Van Poppel, Hendrik; Mukherjee, Som D; Suttmann, Henrik; Gerritsen, Winald R; Flaig, Thomas W; George, Daniel J; Yu, Evan Y; Efstathiou, Eleni; Pantuck, Allan; Winquist, Eric; Higano, Celestia S; Taplin, Mary-Ellen; Park, Youn; Kheoh, Thian; Griffin, Thomas; Scher, Howard I; Rathkopf, Dana E

    2013-01-10

    Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; Pchemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).

  6. Improved survival trends in platinum-resistant patients with advanced ovarian, fallopian or peritoneal cancer treated with first-line paclitaxel/platinum chemotherapy: the impact of novel agents.

    Science.gov (United States)

    Bamias, Aristotle; Bamia, Christine; Zagouri, Flora; Kostouros, Efthimios; Kakoyianni, Konstantina; Rodolakis, Alexandros; Vlahos, George; Haidopoulos, Dimitrios; Thomakos, Nikolaos; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios

    2013-01-01

    The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p improved the prognosis of platinum-resistant patients. Copyright © 2012 S. Karger AG, Basel.

  7. Establishing schedules for repeated doses of strontium and for concurrent chemotherapy in hormone-resistant patients with prostate cancer: measurement of blood and urine strontium levels.

    Science.gov (United States)

    Ben-Yosef, Rami; Pelled, Omer; Marko, Rachel; Vexler, Akiva; Teshuva, Avi; German, Uzi; Levita, Moshe; Kol, Rina

    2005-04-01

    Strontium-89 (Sr-89) alone or with concurrent chemotherapy has a role in the treatment of patients with prostate cancer (PCP). The schedules for repeated doses of Sr-89 or for concurrent chemotherapy is undetermined. The objective of this study was to measure the effective half-life (Te) of Sr-89 using a detector available in a nuclear research facility. Blood and urine samples obtained from PCP treated with Sr-89 (Metastron, Amersham, U.K.) were measured for radioactivity with a High Pure Germanium (HPGe) detector in a gamma spectrometry system (Eurisys, France). Twenty-five urine and 22 blood samples were obtained from 8 patients during a period of 160 days after Metastron injection. Sr-89 radioactivity levels in blood and urine were quite low (radioactivity levels were moderately high and could be detected up to 160 days. Based on Sr-85 urine levels, the calculated Sr-89 Te ranged from 9.6 to 20.7 days. Sr-89 Te can be routinely calculated in PCP based on HPGe detection of Sr-85 radioactivity levels in urine. This measurement can establish schedules for either repeated doses of Sr-89 or concurrent chemotherapy.

  8. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Olsson Björn

    2009-10-01

    Full Text Available Abstract Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH, we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1 plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR to evaluate the impact of DNA alterations on the transcriptional level. Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate

  9. Palliative chemotherapy after failure of high-dose chemotherapy in breast cancer--toxicity and efficacy

    NARCIS (Netherlands)

    Schrama, J. G.; de Boer, M. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

    2003-01-01

    We evaluated the toxicity and efficacy of the first palliative chemotherapy regimen after failure of high-dose chemotherapy in 148 patients with primary or metastatic breast cancer treated with high-dose chemotherapy (one full dose CTC, (cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin

  10. n-3 polyunsaturated fatty acid supplementation during cancer chemotherapy

    OpenAIRE

    Morland, Sarah Louise; Martins, Karen J.B.; Mazurak, Vera C

    2016-01-01

    Evidence from several clinical trials suggests that n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation during cancer chemotherapy improves patient outcomes related to chemotherapy tolerability, regardless of the type of chemotherapy used. While the effects of n-3 PUFA supplementation during chemotherapy have been the subject of several reviews, the mechanisms by which n-3 PUFA improve patient responses through improved chemotherapy tolerability are unclear. There are several barriers c...

  11. NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance

    DEFF Research Database (Denmark)

    Lauritzen, G; Jensen, M B F; Bødtkjer, Ebbe

    2010-01-01

    Altered pH-regulatory ion transport is characteristic of many cancers; however, the mechanisms and consequences are poorly understood. Here, we investigate how a truncated, constitutively active ErbB2 receptor (DeltaNErbB2) common in breast cancer impacts on the Na(+)/H(+)-exchanger NHE1 and the Na......(+),HCO(3)(-)-cotransporter NBCn1 in MCF-7 human breast cancer cells and address the roles of these transporters in chemotherapy resistance. Upon DeltaNErbB2 expression, mRNA and protein levels of NBCn1, yet not of NHE1, increased several-fold, and the localization of both transporters was altered...... cells to cisplatin-induced programmed cell death (PCD) in a caspase-, cathepsin-, and reactive oxygen species-dependent manner. NHE1 inhibition augmented cisplatin-induced caspase activity and lysosomal membrane permeability followed by cysteine cathepsin release. In contrast, NBCn1 inhibition...

  12. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  13. PERK induces resistance to cell death elicited by endoplasmic reticulum stress and chemotherapy.

    Science.gov (United States)

    Salaroglio, Iris C; Panada, Elisa; Moiso, Enrico; Buondonno, Ilaria; Provero, Paolo; Rubinstein, Menachem; Kopecka, Joanna; Riganti, Chiara

    2017-05-12

    Nutrient deprivation, hypoxia, radiotherapy and chemotherapy induce endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein response (UPR). Extensive and acute ER stress directs the UPR towards activation of death-triggering pathways. Cancer cells are selected to resist mild and prolonged ER stress by activating pro-survival UPR. We recently found that drug-resistant tumor cells are simultaneously resistant to ER stress-triggered cell death. It is not known if cancer cells adapted to ER stressing conditions acquire a chemoresistant phenotype. To investigate this issue, we generated human cancer cells clones with acquired resistance to ER stress from ER stress-sensitive and chemosensitive cells. ER stress-resistant cells were cross-resistant to multiple chemotherapeutic drugs: such multidrug resistance (MDR) was due to the overexpression of the plasma-membrane transporter MDR related protein 1 (MRP1). Gene profiling analysis unveiled that cells with acquired resistance to ER stress and chemotherapy share higher expression of the UPR sensor protein kinase RNA-like endoplasmic reticulum kinase (PERK), which mediated the erythroid-derived 2-like 2 (Nrf2)-driven transcription of MRP1. Disrupting PERK/Nrf2 axis reversed at the same time resistance to ER stress and chemotherapy. The inducible silencing of PERK reduced tumor growth and restored chemosensitivity in resistant tumor xenografts. Our work demonstrates for the first time that the adaptation to ER stress in cancer cells produces a MDR phenotype. The PERK/Nrf2/MRP1 axis is responsible for the resistance to ER stress and chemotherapy, and may represent a good therapeutic target in aggressive and resistant tumors.

  14. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  15. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0480 TITLE: Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy PRINCIPAL INVESTIGATOR...Splice Variants and Resistance to Taxane Chemotherapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0480 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...During this reporting period, we have obtained approval for a no-cost extension of this award and change of research focus in the final year. This

  16. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis.

    Science.gov (United States)

    Savage, Philip

    2016-11-21

    Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies. In this review we will examine the cancer stem cell/cancer cell relationship of each of the chemotherapy curable malignancies and how this relationship impacts on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell types. In contrast to the common epithelial cancers, in each of the chemotherapy curable malignancies there are no conventional hierarchical cancer stem cells. However cells with cancer stem like qualities can arise stochastically from within the general tumour cell population. These stochastic stem cells acquire a degree of resistance to DNA damaging agents but also retain much of the key characteristics of the cancer cells from which they develop. We would argue that the balance between the acquired resistance of the stochastic cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell determines the overall chemotherapy curability of each diagnosis. The cancer stem cells in the chemotherapy curable malignancies appear to have two key biological differences from those of the more common chemotherapy incurable malignancies. The first difference is that the conventional hierarchical pattern of cancer stem cells is absent in each of the chemotherapy curable malignancies. The other key difference, we suggest, is that the stochastic stem cells in the chemotherapy curable malignancies

  17. Drug resistance in the mouse cancer clinic

    NARCIS (Netherlands)

    Rottenberg, Sven; Borst, Piet

    2012-01-01

    Drug resistance is one of the most pressing problems in treating cancer patients today. Local and regional disease can usually be adequately treated, but patients eventually die from distant metastases that have become resistant to all available chemotherapy. Although work on cultured tumor cell

  18. A multicenter phase I study of cabazitaxel, mitoxantrone, and prednisone for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: A department of defense prostate cancer clinical trials consortium study.

    Science.gov (United States)

    Aggarwal, Rahul; Bryce, Alan; Ryan, Charles J; Harzstark, Andrea; Derleth, Christina; Kim, Won; Friedlander, Terence; Lin, Amy M; Rodvelt-Bagchi, Tammy; Dhawan, Mallika; Zhang, Li; Lee, Mina; Siebeneck, Eric; Hough, Jeffrey; Small, Eric J

    2017-04-01

    Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile. To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone. Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial. Cabazitaxel 20 and 25mg/m2 were each evaluated in combination with escalating doses of mitoxantrone (starting dose 4mg/m2), given with prednisone 5mg twice daily. A total of 25 patients were enrolled, with median age of 67 (range: 51-78) and prostate-specific antigen of 66.8ng/ml (range: 3-791.2). There were 4 dose-limiting toxicities (febrile neutropenia, n = 3; sepsis, n = 1). The maximally tolerated dose was cabazitaxel 20mg/m2 plus mitoxantrone 12mg/m2. The most common treatment-related grade≥3 related adverse events included neutropenia (n = 8; 32%), febrile neutropenia (n = 5; 20%), and thrombocytopenia (n = 4; 16%). The median number of treatment cycles was 8 (range: 2 to 19+). Decline in prostate-specific antigen to≥50% from baseline was observed in 15 patients (60%). Objective responses were observed in 10/14 (71%) evaluable patients. The median radiographic progression-free survival was 14.5 months (95% CI: 8.0-not reached (NR)), and median overall survival was 23.3 months (95% CI: 14.3-NR). The approved single-agent doses of mitoxantrone and cabazitaxel were safely combined. The combination led to durable tumor responses in most patients. Further study of the combination is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. Meryem Aitelhaj, Siham Lkhoyaali, Ghizlane Rais, Saber Boutayeb, Hassan Errihani ...

  20. Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

    NARCIS (Netherlands)

    deGraaf, H; Dolsma, WV; Willemse, PHB; vanderGraaf, WTA; Sleijfer, DT; deVries, EGE; Mulder, NH

    1997-01-01

    Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed by ablative chemotherapy and chest irradiation. One patient died of subacute heart failure 3 months after ablative chemotherapy. At a minimum of 1 year's follow-up (range 1-11 years) left vertricular

  1. Targeted cancer therapy; nanotechnology approaches for overcoming drug resistance.

    Science.gov (United States)

    Gao, Yan; Shen, Jacson K; Milane, Lara; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Recent advances in cancer molecular biology have resulted in parallel and unprecedented progress in the development of targeted cancer therapy. Targeted therapy can provide higher efficacy and lower toxicity than conventional chemotherapy for cancer. However, like traditional chemotherapy, molecularly targeted cancer therapy also faces the challenge of drug resistance. Multiple mechanisms are responsible for chemotherapy resistance in tumors, including over-expression of efflux transporters, somatic alterations of drug targets, deregulation of apoptosis, and numerous pharmacokinetic issues. Nanotechnology based approaches are proving to be efficacious in overcoming drug resistance in cancer. Combination of targeted therapies with nanotechnology approaches is a promising strategy to overcome targeted therapy drug resistance in cancer treatment. This review discusses the mechanisms of targeted drug resistance in cancer and discusses nanotechnology approaches to circumvent this resistance.

  2. Cancer chemotherapy and cardiac arrhythmias: a review.

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  3. Prostate-specific antigen response rate of sequential chemotherapy in castration-resistant prostate cancer: the results of real life practice

    Directory of Open Access Journals (Sweden)

    Geehyun Song

    2013-09-01

    Conclusions: Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC.

  4. Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy

    DEFF Research Database (Denmark)

    Grassilli, Emanuela; Narloch, Robert; Federzoni, Elena

    2013-01-01

    Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy.......Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy....

  5. ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

    NARCIS (Netherlands)

    Wielenga, Mattheus C. B.; Colak, Selcuk; Heijmans, Jarom; van Lidth de Jeude, Jooske F.; Rodermond, Hans M.; Paton, James C.; Paton, Adrienne W.; Vermeulen, Louis; Medema, Jan Paul; van den Brink, Gijs R.

    2015-01-01

    Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to

  6. Concurrent chemotherapy and radiotherapy for cervical cancer.

    Science.gov (United States)

    Martín-Martínez, A; Molano, F; Lloret, M; Falcón-Vizcaino, O; García-Hernández, J A

    2003-01-01

    To compare the results obtained following treatment, from a group of patients with locally advanced cervical cancer (Stage IB or higher) treated with concurrent chemotherapy and radiotherapy in relation to a group of patients treated exclusively with radiotherapy. All patients treated with concurrent chemotherapy and radiotherapy at the Gynaecologic Oncology Unit of the University Hospital Materno Infantil of the Canaries between 1999 and 2000, both inclusive, were included. The first group to be considered was formed by patients who received combined treatment. The second group of patients received radiotherapy exclusively, having been treated in previous years (1997-1998 period). The results were compared in relation to survival in the two following years from treatment (2000-2001) in the group of combined treatment and years 1999-2000 in the group that received only radiotherapy. To compare the survival of both groups the chi-square test and Odds Ratio were utilised. The groups compared are homogeneous when looking at the stage of the disease when diagnosed, the histological type of tumour and its degree of cellular differentiation, the CAT results and tumoral markers. Survival of more than two years was observed in the group treated with concurrent chemotherapy and radiotherapy in relation to the group treated exclusively with radiotherapy; chi-square 9.92, p < 0.01, OR: 0.1 (0.01-0.6).

  7. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer

    Science.gov (United States)

    Bhola, Neil E.; Balko, Justin M.; Dugger, Teresa C.; Kuba, María Gabriela; Sánchez, Violeta; Sanders, Melinda; Stanford, Jamie; Cook, Rebecca S.; Arteaga, Carlos L.

    2013-01-01

    After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8–dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC. PMID:23391723

  8. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  9. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  10. Acupuncture as a complementary treatment for cancer patients receiving chemotherapy.

    Science.gov (United States)

    Tas, Demet; Uncu, Dogan; Sendur, Mehmet Ali; Koca, Nuran; Zengin, Nurullah

    2014-01-01

    Medical treatment for eliminating the side effects of cancer therapy may not always be efficacious. Acupuncture is one of the most widely accepted alternative and complementary therapies in use today. In this study, we investigated the efficacy of acupuncture in patients experiencing cancer treatment side effects, including nausea, vomiting, pain, poor sleep quality and anxiety. A total of 45 inpatients who underwent chemotherapy between February and April 2013 in the Oncology Department of Numune Hospital were included in our study. Acupuncture was administered to the patients one day prior to chemotherapy, on the day of chemotherapy and one day after chemotherapy. The patients were evaluated on nausea, vomiting, pain, sleep quality and anxiety before the chemotherapy and on the 4th day of chemotherapy. Of the 45 patients included in the study, 18 (40%) were female and 27 (60%) were male. A total of 25 (55.6%) had an elementary school education; 32 patients (71%) had stage 4 cancer and were treated with palliative chemotherapy (the patient characteristics are shown in Table 1). Statistically significant decreases (panxiety scores were observed after the acupuncture treatment compared to baseline. There were no differences in the age, gender, education level, stage or metastasis levels between the patient groups whose symptoms improved or were unchanged. Our study showed that acupuncture has positive effects in cancer treatment patients who experience nausea, vomiting, pain, poor sleep quality and anxiety as side effects of chemotherapy. Chemotherapy-related side effects in cancer patients could be decreased by the concurrent use of acupuncture.

  11. ERG induces taxane resistance in castration-resistant prostate cancer

    Science.gov (United States)

    Galletti, Giuseppe; Matov, Alexandre; Beltran, Himisha; Fontugne, Jacqueline; Miguel Mosquera, Juan; Cheung, Cynthia; MacDonald, Theresa Y.; Sung, Matthew; O’Toole, Sandra; Kench, James G.; Suk Chae, Sung; Kimovski, Dragi; Tagawa, Scott T.; Nanus, David M.; Rubin, Mark A.; Horvath, Lisa G.; Giannakakou, Paraskevi; Rickman, David S.

    2014-01-01

    Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches. PMID:25420520

  12. Drug cocktail optimization in chemotherapy of cancer.

    Directory of Open Access Journals (Sweden)

    Saskia Preissner

    Full Text Available BACKGROUND: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP. Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. OBJECTIVE: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. DATA SOURCES AND METHODS: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. RESULTS: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

  13. Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A

    Science.gov (United States)

    Lotti, Fiorenza; Jarrar, Awad M.; Pai, Rish K.; Hitomi, Masahiro; Lathia, Justin; Mace, Adam; Gantt, Gerald A.; Sukhdeo, Kumar; DeVecchio, Jennifer; Vasanji, Amit; Leahy, Patrick; Hjelmeland, Anita B.

    2013-01-01

    Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers. Colorectal CICs were resistant to conventional chemotherapy in cell-autonomous assays, but CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs). Comparative analysis of matched colorectal cancer specimens from patients before and after cytotoxic treatment revealed a significant increase in CAFs. Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor growth associated with increased secretion of specific cytokines and chemokines, including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A was overexpressed by colorectal CAFs in response to chemotherapy with expression validated directly in patient-derived specimens without culture. These data suggest that chemotherapy induces remodeling of the tumor microenvironment to support the tumor cellular hierarchy through secreted factors. Incorporating simultaneous disruption of CIC mechanisms and interplay with the tumor microenvironment could optimize therapeutic targeting of cancer. PMID:24323355

  14. Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers.

    Science.gov (United States)

    Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro; Ivan, Cristina; Rodriguez-Aguayo, Cristian; Fuentes-Mattei, Enrique; Xiao, Lianchun; Vannini, Ivan; Redis, Roxana S; D'Abundo, Lucilla; Zhang, Xinna; Nicoloso, Milena S; Rossi, Simona; Gonzalez-Villasana, Vianey; Rupaimoole, Rajesha; Ferracin, Manuela; Morabito, Fortunato; Neri, Antonino; Ruvolo, Peter P; Ruvolo, Vivian R; Pecot, Chad V; Amadori, Dino; Abruzzo, Lynne; Calin, Steliana; Wang, Xuemei; You, M James; Ferrajoli, Alessandra; Orlowski, Robert; Plunkett, William; Lichtenberg, Tara M; Davuluri, Ramana V; Berindan-Neagoe, Ioana; Negrini, Massimo; Wistuba, Ignacio I; Kantarjian, Hagop M; Sood, Anil K; Lopez-Berestein, Gabriel; Keating, Michael J; Fabbri, Muller; Calin, George A

    2017-06-01

    Purpose: The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors.Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo We show that anti-miR-155-DOPC can be considered non-toxic in vivo We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer.Conclusions: Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death. Clin Cancer Res; 23(11); 2891-904. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    Science.gov (United States)

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

    2011-02-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  17. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Evans, Christopher P; Higano, Celestia S; Keane, Thomas; Andriole, Gerald; Saad, Fred; Iversen, Peter; Miller, Kurt; Kim, Choung-Soo; Kimura, Go; Armstrong, Andrew J; Sternberg, Cora N; Loriot, Yohann; de Bono, Johann; Noonberg, Sarah B; Mansbach, Hank; Bhattacharya, Suman; Perabo, Frank; Beer, Tomasz M; Tombal, Bertrand

    2016-10-01

    Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195). Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease-benefitted from enzalutamide, an active well-tolerated therapy

  18. Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    2015-12-01

    Conclusions: In summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy.

  19. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    OpenAIRE

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarr...

  20. Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy

    Science.gov (United States)

    Gad, Aniket; Kydd, Janel; Piel, Brandon; Rai, Prakash

    2016-01-01

    Cancer forms exhibiting poor prognosis have been extensively researched for therapeutic solutions. One of the conventional modes of treatment, chemotherapy shows inadequacy in its methodology due to imminent side-effects and acquired drug-resistance by cancer cells. However, advancements in nanotechnology have opened new frontiers to significantly alleviate collateral damage caused by current treatments via innovative delivery techniques, eliminating pitfalls encountered in conventional treatments. Properties like reduced drug-clearance and increased dose efficacy by the enhanced permeability and retention effect deem nanoparticles suitable for this application. Optimization of size, surface charge and surface modifications have provided nanoparticles with stealth properties capable of evading immune responses, thus deeming them as excellent carriers of chemotherapeutic agents. Biocompatible and biodegradable forms of polymers enhance the bioavailability of chemotherapeutic agents, and permit a sustained and time-dependent release of drugs which is a characteristic of their composition, thereby providing a controlled therapeutic approach. Studies conducted in vitro and animal models have also demonstrated a synergism in cytotoxicity given the mechanism of action of anticancer drugs when administered in combination providing promising results. Combination therapy has also shown implications in overcoming multiple-drug resistance, which can however be subdued by the adaptable nature of tumor microenvironment. Surface modifications with targeting moieties can therefore feasibly increase nanoparticle uptake by specific receptor-ligand interactions, increasing dose efficacy which can seemingly overcome drug-resistance. This article reviews recent trends and investigations in employing polymeric nanoparticles for effectively delivering combination chemotherapy, and modifications in delivery parameters enhancing dose efficacy, thus validating the potential in this

  1. Preoperative chemotherapy treatment of breast cancer--a review.

    Science.gov (United States)

    Buzdar, Aman U

    2007-12-01

    Despite proven benefits of neoadjuvant chemotherapy in patients with locally advanced, invasive breast cancer, no regimen is recommended as the treatment of choice. Neoadjuvant chemotherapy regimens encompass single-agent and combination therapy and sequential treatment. For this report, the author reviewed the literature to determine which regimen, if any, was most beneficial. The results indicated that studies have yielded a wide range of response rates, but no single regimen has emerged as a clear leader. The literature is compounded further by lack of standardized criteria to determine pathologic complete response (which is predictive of survival benefits) and between-study variation in the stringency by which this endpoint is defined. Given the lack of a preferred treatment regimen in the neoadjuvant setting, identifying patients who are likely to respond to specific agents could inform treatment decisions, improve treatment outcomes, and aid in avoiding unnecessary exposure to potential toxicities. The development of novel agents for use alone or in combination with existing agents may improve response rates further in the neoadjuvant setting, especially because a significant proportion of breast tumors can be resistant to many current antineoplastic agents. Particularly noteworthy are the epothilones and their analogs because of their low susceptibility to common tumor-resistance mechanisms. Initial data have indicated that ixabepilone, which is an epothilone analog, has activity in the neoadjuvant setting, and predictive factors for response have been identified. The future of neoadjuvant therapy lies in tailoring treatment to individual patients by identifying response predictors and developing novel agents. This ultimately may lead to improved outcomes for women with breast cancer. Copyright (c) 2007 American Cancer Society.

  2. Breast Cancer Patients’ Cognitive Functioning Before and After Chemotherapy

    DEFF Research Database (Denmark)

    Andersen, Christina Maar; Pedersen, Anette Fischer; Mehlsen, Mimi Yung

    chemotherapy which interfere with their abilities to fulfill social and work-related responsibilities. However, since the cause of the cognitive problems is unknown, it is difficult for GPs to offer appropriate counseling on this issue. Aim: To conduct a systematic review and meta-analysis of the available...... evidence concerning cognitive functioning of breast cancer patients before and after chemotherapy. Methods: The databases PubMed and SSCI were searched for articles on the cognitive functioning of breast cancer patients receiving chemotherapy. The search took place from August to December 2010 and extended...... as far back as the databases allowed. Seven studies were selected based on three inclusion criteria: prospective studies, use of neuropsychological tests and inclusion of two patient groups: one receiving chemotherapy and one not receiving chemotherapy (control group). Results: At baseline, breast cancer...

  3. Acute constipation in children receiving chemotherapy for cancer.

    Science.gov (United States)

    Pashankar, Farzana D; Season, J Hale; McNamara, Joseph; Pashankar, Dinesh S

    2011-10-01

    Constipation occurs in children receiving chemotherapy for cancer but there are no data about prevalence, risk factors, and severity of constipation in this group of children. We prospectively studied 61 children receiving chemotherapy for cancer. We administered questionnaires to children and parents and collected data on demographics, chemotherapy, and bowel movement pattern during chemotherapy. We used North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria for the diagnosis of constipation. Parental perception of constipation as a problem and impact on lifestyle during chemotherapy were assessed on a 0 to 3 scale with 0 being no problem, 1 minor, 2 significant, and 3 being a major problem. Thirty-five children (57%) had acute constipation lasting for 2 or more weeks during chemotherapy. Several risk factors were analyzed and only combined use of vincristine and opiates emerged as significant risk factor for the development of constipation. In children with constipation, 15 of 35 parents (43%) perceived constipation as a major/significant problem and 8 children and their parents (23%) perceived constipation having a major/significant impact on lifestyle during chemotherapy. Acute constipation was diagnosed in 57% of children receiving chemotherapy for cancer. Combined use of vincristine and opiates was associated with the development of constipation. Constipation can be a significant problem with a negative impact on lifestyle during chemotherapy and needs aggressive management.

  4. In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model

    Science.gov (United States)

    Sun, Zhongchan; Song, Xinxing; Li, Xiujuan; Su, Tao; Qi, Shun; Qiao, Ruirui; Wang, Fu; Huan, Yi; Yang, Weidong; Wang, Jing; Nie, Yongzhan; Wu, Kaichun; Gao, Mingyuan; Cao, Feng

    2014-11-01

    miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug

  5. Variations of blood glucose in cancer patients during chemotherapy

    African Journals Online (AJOL)

    2016-05-23

    May 23, 2016 ... such as infections and nonmalignancy‑related mortality. The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders.[4,5]. Variations of blood glucose in cancer patients during chemotherapy. J Yang, B Jia, Y Qiao, W Chen, ...

  6. Efflux Pump‑Mediated Resistance in Chemotherapy

    African Journals Online (AJOL)

    to elucidate their structure and mechanisms of action so as to integrate the efflux pump mechanisms in the design and development ... mechanism is very common in resistance to tetracyclines, erythromycin, and fluoroquinolones. ... Antibiotics can act as inducers and regulators of expression of efflux pumps.[7] Several efflux ...

  7. Preventing Fatigue in Patients With Breast Cancer Treated with Chemotherapy

    National Research Council Canada - National Science Library

    Marrow, Gary

    2001-01-01

    ... or alleviate the development of treatment-induced fatigue. We conducted a randomized, double-blind, placebo-controlled clinical trial with 124 breast cancer patients who were studied for up to four successive chemotherapy treatments...

  8. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

    2009-01-01

    Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

  9. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Science.gov (United States)

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  10. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Science.gov (United States)

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  11. Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway.

    Science.gov (United States)

    Zhong, Jia-Teng; Yu, Jian; Wang, Hai-Jun; Shi, Yu; Zhao, Tie-Suo; He, Bao-Xia; Qiao, Bin; Feng, Zhi-Wei

    2017-05-01

    Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway-related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V-fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin

  12. Overcoming Drug Resistance in Pancreatic Cancer

    Science.gov (United States)

    Long, Jiang; Zhang, Yuqing; Yu, Xianjun; Yang, Jingxuan; LeBrun, Drake; Chen, Changyi; Yao, Qizhi; Li, Min

    2011-01-01

    Introduction Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies. Areas covered Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer, and potential strategies to overcome this. Expert Opinion Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers. PMID:21391891

  13. Primary systemic chemotherapy of breast cancer: indication and predictive factors.

    Science.gov (United States)

    Jinno, Hiromitsu; Sakata, Michio; Hayashida, Tetsu; Takahashi, Maiko; Sato, Tomomi; Seki, Hirohito; Kitagawa, Yuko

    2011-04-01

    Primary systemic chemotherapy has become a standard of care for operable breast cancer patients who are candidates for adjuvant chemotherapy. Induction of pathological complete response (pCR) is one of the main goals of primary systemic chemotherapy because patients with pCR have shown a better prognosis. The definition of pCR has varied across clinical trials. It would be ideal for all researchers to use the same terminology in describing pathologic response. Identification of accurate predictive factors of pCR to primary systemic chemotherapy is urgent, because patients with a low chance of pCR and clinical response should be spared unnecessary toxicity. Early response to primary systemic chemotherapy might be correlated with a high probability of a pCR. Therefore, evaluation of early response is useful to avoid unnecessary toxicity without potential benefit from chemotherapy.

  14. Metallic taste in cancer patients treated with chemotherapy.

    Science.gov (United States)

    IJpma, I; Renken, R J; Ter Horst, G J; Reyners, A K L

    2015-02-01

    Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients. Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies. Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents. Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Coping strategies used by hospitalized children with cancer undergoing chemotherapy.

    Science.gov (United States)

    Sposito, Amanda Mota Pacciulio; Silva-Rodrigues, Fernanda Machado; Sparapani, Valéria de Cássia; Pfeifer, Luzia Iara; de Lima, Regina Aparecida Garcia; Nascimento, Lucila Castanheira

    2015-03-01

    To analyze coping strategies used by children with cancer undergoing chemotherapy during hospitalization. This was an exploratory study to analyze qualitative data using an inductive thematic analysis. Semistructured interviews using puppets were conducted with 10 children with cancer, between 7 and 12 years old, who were hospitalized and undergoing chemotherapy. The coping strategies to deal with chemotherapy were: understanding the need for chemotherapy; finding relief for the chemotherapy's side effects and pain; seeking pleasure in nourishment; engaging in entertaining activities and having fun; keeping the hope of cure alive; and finding support in religion. Children with cancer undergoing chemotherapy need to cope with hospitalizations, pain, medication side effects, idle time, and uncertainty regarding the success of treatment. These challenges motivated children to develop their own coping strategies, which were effective while undergoing chemotherapy. By gaining knowledge and further understanding about valid coping strategies during chemotherapy treatment, health professionals can mobilize personal and material resources from the children, health teams, and institutions aiming to potentiate the use of these strategies to make treatments the least traumatic. © 2015 Sigma Theta Tau International.

  16. Chemotherapy resistance of mouse WAP-SVT/t breast cancer cells is mediated by osteopontin, inhibiting apoptosis downstream of caspase-3.

    Science.gov (United States)

    Graessmann, M; Berg, B; Fuchs, B; Klein, A; Graessmann, A

    2007-05-03

    Impairment of the complex regulatory network of cell death and survival is frequently the reason for therapy resistance of breast cancer cells and a major cause of tumor progression. We established two independent cell lines from a fast growing mouse breast tumor (WAP-SVT/t transgenic animal). Cells from one line (ME-A cells) are sensitive to apoptotic stimuli such as growth factor depletion or treatment with antitumor agents (e.g. doxorubicin). Cells from the second line (ME-C cells), which carry a missense mutation at the p53 codon 242, are very insensitive to apoptotic stimuli. Co-cultivation experiments revealed that the ME-C cells mediate cell death resistance to the ME-A cells. Microarray and Western blot analysis showed that osteopontin (OPN) is selectively overexpressed by the ME-C cells. This glycoprotein is the most abundant protein secreted by the ME-C cells and we obtained strong indications that OPN is the main antiapoptotic factor. However, the OPN containing ME-C cell medium does not alter the expression level of pro- or antiapoptotic genes or known inhibitors of apoptosis (IAPs). Its signaling involves mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)1/2 as the kinase inhibitor PD98059 restores apoptosis but not the Akt inhibitor. In the ME-A cells, mitochondrial cytochrome c release occurs with and without external apoptotic stimuli. OPN containing ME-C cell medium does not prevent the mitochondrial cytochrome c release and caspase-9 processing. In serum starved ME-A cells, the OPN containing ME-C cell medium prevents caspase-3 activation. However, in doxorubicin-treated cells, although apoptosis is blocked, it does not inhibit caspase-3. This indicates that the ME-A cells distinguish between the initial apoptotic stimuli and that the cells possess a further uncharacterized control element acting downstream from caspase-3.

  17. Non-cross resistant sequential single agent chemotherapy in first-line advanced non-small cell lung cancer patients: Results of a phase II study

    NARCIS (Netherlands)

    V. Surmont; J.G.J.V. Aerts (Joachim); K.Y. Tan; F.M.N.H. Schramel (Franz); R. Vernhout (Rene); H.C. Hoogsteden (Henk); R.J. van Klaveren (Rob)

    2009-01-01

    textabstractBackground. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell

  18. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  19. Clinical implications of chemotherapy-induced tumor gene expression in human breast cancers.

    Science.gov (United States)

    Tan, Sing-Huang; Lee, Soo-Chin

    2010-03-01

    There has been much interest in generating gene signatures to predict treatment response in breast cancer. There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline studies, there have been at least 8 published studies evaluating chemotherapy-induced tumor genomic changes over time in human breast cancers. Studies on chemotherapy-induced gene expression changes were reviewed in detail. Drug-induced biological changes within the tumor shed light on mechanisms of drug resistance and provided valuable insights regarding genes and pathways that were regulated by different drugs, including therapeutic targets that could be exploited to overcome resistance. One study also suggested post-chemotherapy gene signatures to be more predictive of response and survival than the unchallenged baseline signatures. Studies on chemotherapy-induced changes, although informative, are logistically demanding to execute, often with significant attrition of collected samples resulting in small datasets. They are further limited by heterogeneity of study population, chemotherapy regimens used, timing of the post-therapy sample and definition of response endpoint, making cross-comparisons of studies and data interpretation difficult. Future studies should address these limitations, and should involve larger sample sets and prospective studies for validation.

  20. The Utilization of the Immune System in Lung Cancer Treatment: Beyond Chemotherapy

    Directory of Open Access Journals (Sweden)

    Carmen W. H. Chan

    2016-02-01

    Full Text Available Lung cancer is ranked first worldwide as one of the main cancers in terms of prevalence and mortality rate. The development of effective treatment strategies against lung cancer is therefore of paramount importance. Traditionally, chemotherapy was employed in the treatment of various cancers. However, the non-specific nature of the actions of chemotherapeutic drugs and the potential for tumors to develop resistance to these drugs may render chemotherapy a less favorable option for cancer treatment. Immunotherapy provides an alternative strategy for this purpose. It involves the utilization of the immune system and the immune effector cells to elicit an immune response to the tumors, thereby eliminating them. Strategies include the administration of pro-inflammatory cytokines for immune stimulation, the removal of immunological checkpoints using monoclonal antibodies, and the use of cancer vaccines to enhance immunity against tumors. This article summarizes the above strategies, highlights the reasons why immunotherapy is superior to chemotherapy for the purpose of tumor removal, and reviews the recent clinical studies comparing the clinical outcomes of patients undergoing immunotherapy and chemotherapy. The article also describes advances in immunotherapeutic strategies for the treatment of lung cancer.

  1. 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

    2015-10-01

    Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. 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. This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Patients were grouped by concomitant BTT use or no BTT use. 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. 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; pAA 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 AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and

  2. Aggressive chemotherapy and the selection of drug resistant pathogens.

    Directory of Open Access Journals (Sweden)

    Silvie Huijben

    2013-09-01

    Full Text Available Drug resistant pathogens are one of the key public health challenges of the 21st century. There is a widespread belief that resistance is best managed by using drugs to rapidly eliminate target pathogens from patients so as to minimize the probability that pathogens acquire resistance de novo. Yet strong drug pressure imposes intense selection in favor of resistance through alleviation of competition with wild-type populations. Aggressive chemotherapy thus generates opposing evolutionary forces which together determine the rate of drug resistance emergence. Identifying treatment regimens which best retard resistance evolution while maximizing health gains and minimizing disease transmission requires empirical analysis of resistance evolution in vivo in conjunction with measures of clinical outcomes and infectiousness. Using rodent malaria in laboratory mice, we found that less aggressive chemotherapeutic regimens substantially reduced the probability of onward transmission of resistance (by >150-fold, without compromising health outcomes. Our experiments suggest that there may be cases where resistance evolution can be managed more effectively with treatment regimens other than those which reduce pathogen burdens as fast as possible.

  3. Species differences in tumour responses to cancer chemotherapy

    Science.gov (United States)

    Lawrence, Jessica; Cameron, David; Argyle, David

    2015-01-01

    Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies. PMID:26056373

  4. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis

    DEFF Research Database (Denmark)

    De Roock, Wendy; Claes, Bart; Bernasconi, David

    2010-01-01

    Following the discovery that mutant KRAS is associated with resistance to anti-epidermal growth factor receptor (EGFR) antibodies, the tumours of patients with metastatic colorectal cancer are now profiled for seven KRAS mutations before receiving cetuximab or panitumumab. However, most patients...... with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre...

  5. Variations of blood glucose in cancer patients during chemotherapy ...

    African Journals Online (AJOL)

    Purpose: The aim of this study was to analyze the blood glucose (BG) variations in cancer patients during chemotherapy according to tumor types and chemotherapeutic regimens. Materials and Methods: Patients were examined from the Department of Medical Oncology of Cancer Hospital and Institute, Chinese Academy ...

  6. Chemotherapy and its evolving role in the management of advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Michael T Schweizer

    2014-06-01

    Full Text Available Advanced prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins first described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer (CRPC. Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing 'level-1 evidence' that docetaxel-based chemotherapy led to prolongation in overall survival (OS. This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efficacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents (e.g. abiraterone and enzalutamide have also been shown to lead to a survival benefit in men with CRPC. With so many new treatment options available, a number of questions remain. These include: how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may benefit most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era.

  7. Chemotherapy and its evolving role in the management of advanced prostate cancer

    Science.gov (United States)

    Schweizer, Michael T; Antonarakis, Emmanuel S

    2014-01-01

    Advanced prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins first described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer (CRPC). Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing ‘level-1 evidence’ that docetaxel-based chemotherapy led to prolongation in overall survival (OS). This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efficacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents (e.g. abiraterone and enzalutamide) have also been shown to lead to a survival benefit in men with CRPC. With so many new treatment options available, a number of questions remain. These include: how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may benefit most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era. PMID:24435058

  8. Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Seredina Tatyana A

    2012-06-01

    Full Text Available Abstract Background The enzymes of the cytochrome P450 family (CYPs play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91, as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12 when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91 in the population of interest.

  9. Factors affecting receipt of chemotherapy in women with breast cancer

    Directory of Open Access Journals (Sweden)

    Libby Morimoto

    2010-05-01

    Full Text Available Libby Morimoto1, Jenna Coalson1, Fionna Mowat1, Cynthia O’Malley21Exponent Health Sciences, Menlo Park, CA, USA; 2Amgen Global Epidemiology, Thousand Oaks, CA, USAAims: To review literature describing factors associated with receipt of chemotherapy for breast cancer, to better understand what factors are most relevant to women’s health and whether health disparities are apparent, and to assess how these factors might affect observational studies and outcomes research. Patterns of care for metastatic breast cancer, for which no standard-of-care exists, were of particular interest.Methods: Relevant studies written in English, Italian, French, or Spanish, published in 2000 or later, were identified through MEDLINE and reviewed. Review articles and clinical trials were excluded; all observational studies and surveys were considered. Articles were reviewed for any discussion of patient characteristics, hospital/physician/insurance characteristics, psychosocial characteristics, and clinical characteristics affecting receipt of chemotherapy by breast cancer patients.Results: In general, factors associated with increased likelihood of receiving chemotherapy included younger age, being Caucasian, having good general health and few co-morbidities, having more severe clinical disease, having responded well to previous treatment, and having breast cancer that is estrogen- or progesterone-receptor-negative. Many of the clinical factors found to increase the likelihood of receiving chemotherapy were consistent with current oncology guidelines. Of the relevant 19 studies identified, only six (32% reported data specific to metastatic cancer; most studies aggregated women with stage I–IV for purposes of analysis.Conclusion: Studies of patterns of care in breast cancer treatment can help identify challenges in health care provided to particular subgroups of women and can aid researchers in designing studies that account for such factors in clinical and

  10. Ginger Helps Reduce Nausea from Chemotherapy | Division of Cancer Prevention

    Science.gov (United States)

    Ginger helped prevent or reduce chemotherapy-induced nausea when taken with traditional anti-nausea drugs by patients with cancer, researchers have found. The results are from a randomized, double-blind, placebo-controlled clinical trial, the largest study to examine the potential effects of ginger on chemotherapy-related nausea. The study will be presented May 30 at the ASCO annual meeting in Orlando, FL. |

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  12. Effect of interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy on the malignant biological behavior of advanced bladder cancer

    Directory of Open Access Journals (Sweden)

    Hong-Mei Zhang

    2017-09-01

    Full Text Available Objective: To study the effect of interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy on the malignant biological behavior of advanced bladder cancer. Methods: Patients with advanced bladder cancer who were treated in Tongcheng People’s Hospital between April 2015 and July 2016 were selected as the research subjects and randomly divided into group A who received interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy and the group B who received pirarubicin infusion chemotherapy combined with systemic chemotherapy. The contents of tumor markers and cytokines and the expression of apoptosis molecules in the urine were detected before and after chemotherapy. Results: 8 weeks after chemotherapy, BLCA-1, BLCA-4, CYFRA21-1, TGF-β1, VEGF, EGF, HGF and IGF-2 contents in urine of both groups of patients were significantly lower than those before treatment, Fas, Bad, PTEN and Beclin-1 mRNA expression in urine were significantly higher than those before treatment and BLCA-1, BLCA-4, CYFRA21-1, TGF-β1, VEGF, EGF, HGF and IGF-2 contents in urine of group A were significantly lower than those of group B, Fas, Bad, PTEN and Beclin-1 mRNA expression in urine were significantly higher than those of group B. Conclusion: Interleukin-2 + pirarubicin infusion chemotherapy combined with systemic chemotherapy can be more effective than pirarubicin infusion chemotherapy combined with systemic chemotherapy in inhibiting the malignant biological behavior of advanced bladder cancer.

  13. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

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

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

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

  15. Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2016-01-01

    Full Text Available In spite of the declining incidence of gastric cancer (GC in recent years, the mortality rate is still high. The asymptomatic nature and nonspecific clinical manifestations combined with the lack of efficient screening programs delay the diagnosis of GC. Therefore, the prevalence of advanced gastric cancer (AGC has prompted the need for aggressive and intensive treatment options. Among the various treatment options for AGC, surgery is still the mainstay. However, the efficacy of surgery alone is not established. Results from multiple randomized controlled trials suggest that preoperative chemotherapy is promising intervention for the treatment and management of AGC. The main objective of neoadjuvant chemotherapy is to downstage or control micrometastasis in resectable tumor before surgery. On the other hand, conversion chemotherapy refers to surgical treatment aiming at R0 resection after chemotherapy for originally nonresectable or marginally resectable tumors. Nevertheless, preoperative chemoradiotherapy is considered beneficial for AGC patients. Over the last few decades, the combination of chemotherapy and targeted therapy prior to surgery demonstrated great results for the treatment of AGC. The rapid developments in genomics and proteomics have heralded the era of precision medicine. The combination of preoperative chemotherapy and precision medicine may enhance survival in AGC patients.

  16. Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine

    Science.gov (United States)

    Xu, Wei; Beeharry, Maneesh K.; Yan, Min; Zhu, Zhenggang

    2016-01-01

    In spite of the declining incidence of gastric cancer (GC) in recent years, the mortality rate is still high. The asymptomatic nature and nonspecific clinical manifestations combined with the lack of efficient screening programs delay the diagnosis of GC. Therefore, the prevalence of advanced gastric cancer (AGC) has prompted the need for aggressive and intensive treatment options. Among the various treatment options for AGC, surgery is still the mainstay. However, the efficacy of surgery alone is not established. Results from multiple randomized controlled trials suggest that preoperative chemotherapy is promising intervention for the treatment and management of AGC. The main objective of neoadjuvant chemotherapy is to downstage or control micrometastasis in resectable tumor before surgery. On the other hand, conversion chemotherapy refers to surgical treatment aiming at R0 resection after chemotherapy for originally nonresectable or marginally resectable tumors. Nevertheless, preoperative chemoradiotherapy is considered beneficial for AGC patients. Over the last few decades, the combination of chemotherapy and targeted therapy prior to surgery demonstrated great results for the treatment of AGC. The rapid developments in genomics and proteomics have heralded the era of precision medicine. The combination of preoperative chemotherapy and precision medicine may enhance survival in AGC patients. PMID:28105420

  17. GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

    Science.gov (United States)

    Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

    2017-01-01

    CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other

  18. 76 FR 21368 - Evaluation of the Potential Developmental Effects of Cancer Chemotherapy During Pregnancy: Call...

    Science.gov (United States)

    2011-04-15

    ... Pregnancy: Call for Information and Nomination of Scientific Experts AGENCY: National Institute of... scientific evidence regarding the potential developmental effects of cancer chemotherapy during pregnancy... pregnancy outcomes and long- term health of offspring exposed to cancer chemotherapy agents during pregnancy...

  19. Metronomic chemotherapy: an attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance.

    Science.gov (United States)

    Kareva, Irina; Waxman, David J; Lakka Klement, Giannoula

    2015-03-28

    The administration of chemotherapy at reduced doses given at regular, frequent time intervals, termed 'metronomic' chemotherapy, presents an alternative to standard maximal tolerated dose (MTD) chemotherapy. The primary target of metronomic chemotherapy was originally identified as endothelial cells supporting the tumor vasculature, and not the tumor cells themselves, consistent with the emerging concept of cancer as a systemic disease involving both tumor cells and their microenvironment. While anti-angiogenesis is an important mechanism of action of metronomic chemotherapy, other mechanisms, including activation of anti-tumor immunity and a decrease in acquired therapeutic resistance, have also been identified. Here we present evidence supporting a mechanistic explanation for the improved activity of cancer chemotherapy when administered on a metronomic, rather than an MTD schedule and discuss the implications of these findings for further translation into the clinic. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Differences in dietary intake during chemotherapy in breast cancer patients compared to women without cancer

    NARCIS (Netherlands)

    Vries, de Y.C.; Berg, van den M.M.G.A.; Vries, de J.H.M.; Boesveldt, S.; Kruif, de J.Th.C.M.; Buist, N.; Haringhuizen, A.; Los, M.; Sommeijer, D.W.; Timmer-Bonte, J.H.N.; Laarhoven, van H.W.M.; Visser, M.; Kampman, E.; Winkels, R.M.

    2017-01-01

    Purpose: Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect dietary habits. This study assessed the intake of energy, macronutrients and food groups before and during chemotherapy in breast cancer patients

  1. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN

    Directory of Open Access Journals (Sweden)

    Yaqin eHan

    2013-12-01

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a ‘stocking and glove’ distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves.

  2. Understanding the role of type 1 interferon in resistance to cancer ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Chemotherapy is the main form of treatment for cancer, but it cannot cure most types of cancer. Another form of treatment is immunotherapy, which aims to stimulate cells of the body's immune system (T cells) to kill cancer cells. Unfortunately, cancers may become resistant to T cells in the same way they learned to resist ...

  3. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

    Science.gov (United States)

    Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

    2015-07-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

  4. Characterization and functional analysis of a slow-cycling subpopulation in colorectal cancer enriched by cell cycle inducer combined chemotherapy.

    Science.gov (United States)

    Wu, Feng-Hua; Mu, Lei; Li, Xiao-Lan; Hu, Yi-Bing; Liu, Hui; Han, Lin-Tao; Gong, Jian-Ping

    2017-10-03

    The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo . Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo . Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro . Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.

  5. The association between germline BRCA2 variants and sensitivity to platinum-based chemotherapy among men with metastatic prostate cancer.

    Science.gov (United States)

    Pomerantz, Mark M; Spisák, Sandor; Jia, Li; Cronin, Angel M; Csabai, Istvan; Ledet, Elisa; Sartor, A Oliver; Rainville, Irene; O'Connor, Edward P; Herbert, Zachary T; Szállási, Zoltan; Oh, William K; Kantoff, Philip W; Garber, Judy E; Schrag, Deborah; Kibel, Adam S; Freedman, Matthew L

    2017-09-15

    Breast cancer 2 (BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment. A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and/or underwent treatment at Dana-Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration-resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in BRCA2 based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin/docetaxel chemotherapy, defined according to a decline in prostate-specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between BRCA2 mutation status and response to carboplatin-based chemotherapy were tested using the Fisher exact test, with a 2-sided P value 50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%-88%; P cancer cell lines functionally corroborated these clinical findings. BRCA2-associated, castration-resistant prostate cancer is associated with a higher likelihood of response to carboplatin-based chemotherapy than non-BRCA2-associated prostate cancer. Cancer 2017;123:3532-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

  6. Resistance to chemotherapy: patient variability and cellular heterogeneity.

    Science.gov (United States)

    Kessler, David A; Austin, Robert H; Levine, Herbert

    2014-09-01

    The issue of resistance to targeted drug therapy is of pressing concern, as it constitutes a major barrier to progress in managing cancer. One important aspect is the role of stochasticity in determining the nature of the patient response. We examine two particular experiments. The first measured the maximal response of melanoma to targeted therapy before the resistance causes the tumor to progress. We analyze the data in the context of a Delbruck-Luria type scheme, wherein the continued growth of preexistent resistant cells are responsible for progression. We show that, aside from a finite fraction of resistant cell-free patients, the maximal response in such a scenario would be quite uniform. To achieve the measured variability, one is necessarily led to assume a wide variation from patient to patient of the sensitive cells' response to the therapy. The second experiment is an in vitro system of multiple myeloma cells. When subject to a spatial gradient of a chemotherapeutic agent, the cells in the middle of the system acquire resistance on a rapid (two-week) timescale. This finding points to the potential important role of cell-to-cell differences, due to differing local environments, in addition to the patient-to-patient differences encountered in the first part. See all articles in this Cancer Research section, "Physics in Cancer Research." ©2014 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Fidia Mumtahana

    2014-12-01

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

  8. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  9. Bevacizumab in combination with chemotherapy in platinum-sensitive ovarian cancer

    Directory of Open Access Journals (Sweden)

    Della Pepa C

    2014-06-01

    Full Text Available Chiara Della Pepa, Susana Banerjee Gynecology Unit, The Royal Marsden NHS Foundation Trust, London, UK Abstract: Targeting angiogenesis is proving to be a successful approach in the management of ovarian cancer. The vascular endothelial growth factor inhibitor, bevacizumab, is the first angiogenesis inhibitor to have shown a significant progression-free survival advantage in the Phase III setting. There is now evidence supporting the use of bevacizumab in combination with chemotherapy for first-line and relapsed (platinum-sensitive and resistant ovarian cancer. In this review, we summarize the positive Phase III trial (OCEANS [Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease] that led to European Medicines Agency approval of bevacizumab in platinum-sensitive first relapse and discuss the best use of the drug in this disease. Keywords: antiangiogenic, recurrent, ovarian

  10. Evaluation of patients\\' adherence to chemotherapy for breast cancer

    African Journals Online (AJOL)

    The study aimed to establish the common reasons for non-adherence to drug treatment among breast cancer patients at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria over a ten-year period (Jan 1993 - Dec 2002). Patients\\' adherence and reasons for non-adherence to chemotherapy were ...

  11. Evaluation of patients' adherence to chemotherapy for breast cancer ...

    African Journals Online (AJOL)

    kemrilib

    African Journal of Health Sciences, Volume 15, Number 1, January- March 2008. 22. Evaluation of patients' adherence to chemotherapy for breast cancer. Adewale O Adisa, Olukayode O Lawal, Abdul RK Adesunkanmi. Department of Surgery, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife,. Nigeria.

  12. Rational Choice of Antiemetic Agents during Cancer Chemotherapy

    Science.gov (United States)

    Brigden, Malcolm L.; Wilson, Kenneth S.; Barnett, Jeffrey B.

    1983-01-01

    Nausea and vomiting are major limitations in cancer chemotherapy. Individual susceptibility to nausea varies enormously. There is no ideal antiemetic, but some work with some chemotherapeutic agents, and some are more effective in younger patients. This article describes a flexible, stepped approach using the phenothiazines, metoclopramide, cannabinoids, anticholinergics, antihistamines and others. PMID:21283402

  13. Influenza vaccination in children being treated with chemotherapy for cancer.

    Science.gov (United States)

    Goossen, Ginette M; Kremer, Leontien C M; van de Wetering, Marianne D

    2013-08-01

    Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. 1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP). We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules. Two independent review authors assessed the methodological quality of included studies and extracted the data. We included 1 RCT and 9 CCTs

  14. Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Sarah eCrawford

    2013-06-01

    Full Text Available U.S. SEER data for age-adjusted mortality rates for all cancers combined for all races show only a modest overall 13% decline over the past 35 years. Moreover, the greatest contributor to cancer mortality is treatment resistant metastatic disease. The accepted therapeutic paradigm for the past half century for the treatment of advanced cancers has involved the use of systemic chemotherapy drugs cytotoxic for cycling cells (both normal and malignant during DNA synthesis and/or mitosis. The failure of this therapeutic modality to achieve high level, consistent rates of disease free survival for some of the most common cancers, including tumors of the lung, colon breast, brain, melanoma and others is the focus of this paper. A retrospective assessment of critical milestones in cancer chemotherapy indicates that most successful therapeutic regimens use cytotoxic cell cycle inhibitors in combined, maximum tolerated, dose dense acute treatment regimens originally developed to treat acute lymphoblastic leukemia and some lymphomas. Early clinical successes in this area led to their wholesale application to the treatment of solid tumor malignancies that, unfortunately, has not produced consistent, long-term high cure rates for many common cancers. Important differences in therapeutic sensitivity of leukemias/lymphomas versus solid tumors can be explained by key biological differences that define the treatment resistant solid tumor phenotype. A review of these clinical outcome data in the context of recent developments in our understanding of drug resistance mechanisms characteristic of solid tumors suggests the need for a new paradigm for the treatment of chemotherapy-resistant cancers. In contrast to reductionist approaches, the systemic approach targets both micro-environmental and systemic factors that drive and sustain tumor progression. These systemic factors include dysregulated inflammatory and oxidation pathways shown to be directly implicated in

  15. Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

    Science.gov (United States)

    Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

    2016-04-01

    Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary

  16. Understanding Chemotherapy

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2014-07-01

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

  18. Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Antonarakis, Emmanuel S; Tagawa, Scott T; Galletti, Giuseppe; Worroll, Daniel; Ballman, Karla; Vanhuyse, Marie; Sonpavde, Guru; North, Scott; Albany, Costantine; Tsao, Che-Kai; Stewart, John; Zaher, Atef; Szatrowski, Ted; Zhou, Wei; Gjyrezi, Ada; Tasaki, Shinsuke; Portella, Luigi; Bai, Yang; Lannin, Timothy B; Suri, Shalu; Gruber, Conor N; Pratt, Erica D; Kirby, Brian J; Eisenberger, Mario A; Nanus, David M; Saad, Fred; Giannakakou, Paraskevi

    2017-10-01

    Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates

  19. Predictors of adherence to different types and doses of supervised exercise during breast cancer chemotherapy

    Science.gov (United States)

    2014-01-01

    Background Exercise is beneficial for breast cancer patients during chemotherapy but adherence to different types and doses of exercise is a challenge. The purpose of this study was to examine predictors of adherence to different types and doses of exercise during breast cancer chemotherapy in a multicenter randomized controlled trial. Methods Breast cancer patients in Edmonton, Vancouver, and Ottawa, Canada receiving chemotherapy (N = 301) were randomized to a standard dose of 25–30 minutes of aerobic exercise (STAN), a higher dose of 50–60 minutes of aerobic exercise (HIGH), or a higher dose of 50–60 minutes of combined aerobic and resistance exercise (COMB). Predictors included demographic, medical, fitness, and quality of life variables. Exercise adherence was measured as the percentage of supervised exercise sessions completed. Results Overall adherence to the supervised exercise sessions was 73% (SD = 24%). In a multivariate regression model, six independent predictors explained 26.4% (p exercise adherence. Higher exercise adherence was achieved by breast cancer patients in Vancouver (p exercise limitations (p = 0.009), receiving shorter chemotherapy protocols (p = 0.015), and with higher VO2peak (p = 0.017). Disease stage (p for interaction = 0.015) and body mass index (p for interaction = 0.030) interacted with group assignment to predict adherence. For disease stage, patients with stage I/IIa disease adhered equally well to all three exercise interventions whereas patients with stage IIb/III disease adhered better to the STAN intervention than the two higher dose exercise interventions. For body mass index, healthy weight patients adhered equally well to all three exercise interventions whereas overweight patients adhered best to STAN and worst to COMB; and obese patients adhered best to STAN and worst to HIGH. Conclusions Determinants of exercise adherence in breast cancer patients receiving chemotherapy are

  20. Alternative Methods to Treat Nausea and Vomiting from Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sheikhi

    2015-01-01

    Full Text Available Chemotherapy Induced Nausea and Vomiting (CINV is among the most intensive side effects and critical concerns for patients with cancer. Most of these patients experience nausea and vomiting after chemotherapy. Sometimes, this is so annoying that it may prevent them from continuing the therapy. With the recent advances, a variety of therapeutic methods are innovated and applied to control CINV. Among them, the main methods include medicinal therapy, relaxation, and herbal therapy. Yet, using dexamethasone together with massage therapy and ginger is identified as the most effective method.

  1. Chemotherapy-induced Peripheral Neuropathy | Division of Cancer Prevention

    Science.gov (United States)

    It usually starts in the hands and/or feet and creeps up the arms and legs. Sometimes it feels like a tingling or numbness. Other times, it’s more of a shooting and/or burning pain or sensitivity to temperature. It can include sharp, stabbing pain, and it can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking. An estimated 30 to 40 percent of cancer patients treated with chemotherapy experience these symptoms, a condition called chemotherapy-induced peripheral neuropathy (CIPN). |

  2. Overcome Cancer Cell Drug Resistance Using Natural Products

    Directory of Open Access Journals (Sweden)

    Pu Wang

    2015-01-01

    Full Text Available Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1 in vitro studies using cell line models; (2 serum pharmacology; (3 in vivo studies using animal models; and (4 clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance.

  3. Chemotherapy-induced irreversible alopecia in early breast cancer patients.

    Science.gov (United States)

    Kim, Gun Min; Kim, Sanghwa; Park, Hyung Seok; Kim, Jee Ye; Nam, Sanggen; Park, Seho; Kim, Seung Il; Kim, DoYoung; Sohn, Joohyuk

    2017-06-01

    The purpose of this work is to determine the prevalence of chemotherapy-induced irreversible alopecia (CIIA), which is defined as an alopecia that exists at least 6 months after completion of chemotherapy and factors affecting CIIA in early breast cancer patients. We performed a cross-sectional study. We retrospectively identified breast cancer patients who had received AC (Adriamycin, Cyclophosphamide) or AC-T (AC followed by Taxane) as neoadjuvant or adjuvant chemotherapy. We conducted questionnaire survey regarding alopecia and measured hair density using phototrichogram. From February 2015 to May 2015, among 265 patients who responded properly to the questionnaire, the women who answered they had severe alopecia (alopecia > 50% of scalp) were 19 patients (7.2%). AC-only and AC-T treated patients reported severe alopecia in 2.7% and 10.5%, respectively, which were significantly different (p < 0.001). Mean hair density was 75 hair/cm 2 (range 42-112) and 75.2/cm 2 (range 48.3-102) on occipital area and vertex area, respectively. Hair loss was the most frequent in parietal area (42.6%). Half of total patients (46%) and 73% of CIIA patients regarded that their hair became thinner after chemotherapy CONCLUSIONS: We found that significant proportion of early breast cancer patients were suffering from severe CIIA, especially when they had been treated with AC followed by taxane regimen.

  4. Randomized controlled trial of the effects of high intensity and low-to-moderate intensity exercise on physical fitness and fatigue in cancer survivors: results of the Resistance and Endurance exercise After ChemoTherapy (REACT) study.

    Science.gov (United States)

    Kampshoff, Caroline S; Chinapaw, Mai J M; Brug, Johannes; Twisk, Jos W R; Schep, Goof; Nijziel, Marten R; van Mechelen, Willem; Buffart, Laurien M

    2015-10-29

    International evidence-based guidelines recommend physical exercise to form part of standard care for all cancer survivors. However, at present, the optimum exercise intensity is unclear. Therefore, we aimed to evaluate the effectiveness of a high intensity (HI) and low-to-moderate intensity (LMI) resistance and endurance exercise program compared with a wait list control (WLC) group on physical fitness and fatigue in a mixed group of cancer survivors who completed primary cancer treatment, including chemotherapy. Overall, 277 cancer survivors were randomized to 12 weeks of HI exercise (n = 91), LMI exercise (n = 95), or WLC (n = 91). Both interventions were identical with respect to exercise type, duration and frequency, and only differed in intensity. Measurements were performed at baseline (4-6 weeks after primary treatment) and post-intervention. The primary outcomes were cardiorespiratory fitness (peakVO2), muscle strength (grip strength and 30-second chair-stand test), and self-reported fatigue (Multidimensional Fatigue Inventory; MFI). Secondary outcomes included health-related quality of life, physical activity, daily functioning, body composition, mood, and sleep disturbances. Multilevel linear regression analyses were performed to estimate intervention effects using an intention-to-treat principle. In the HI and LMI groups, 74 % and 70 % of the participants attended more than 80 % of the prescribed exercise sessions, respectively (P = 0.53). HI (β = 2.2; 95 % CI, 1.2-3.1) and LMI (β = 1.3; 95 % CI, 0.3-2.3) exercise showed significantly larger improvements in peakVO2 compared to WLC. Improvements in peakVO2 were larger for HI than LMI exercise (β = 0.9; 95 % CI, -0.1 to 1.9), but the difference was not statistically significant (P = 0.08). No intervention effects were found for grip strength and the 30-second chair-stand test. HI and LMI exercise significantly reduced general and physical fatigue and reduced activity

  5. Treatment Outcome and Relevance of Palliative Chemotherapy in Urachal Cancer.

    Science.gov (United States)

    Jung, Hyun Ae; Sun, Jong-Mu; Park, Se Hoon; Kwon, Ghee Young; Lim, Ho Yeong

    2014-01-01

    Urachal cancer is a rare malignancy that accounts for cancers. There is currently no consensus on the diagnosis and management of urachal cancer and there are very few reports on palliative chemotherapy for unresectable disease. We delineate the clinical features and treatment outcome of urachal cancer, in particular the relevance of palliative chemotherapy in recurrent, metastatic disease. The clinicopathologic variables and treatment outcome of patients who were treated for urachal cancer were retrospectively reviewed. Among 28 eligible patients, 25 had localized disease and 3 had metastatic disease at initial diagnosis. All patients with localized disease underwent curative resection and there was disease recurrence in 10. Out of 13 patients with metastatic disease either at initial diagnosis or during follow-up, the lung was the most common metastatic site (n = 5), followed by the liver, bone and peritoneum. Ten patients received palliative chemotherapy. A total of 24 chemotherapeutic regimens were administered; regimens with a base of fluoropyrimidine (5-FU), taxane and gemcitabine were the most common. The overall response rate of all chemotherapeutic regimens was 16.7%. The 5-FU-based regimens showed a good response, with 2 of 4 patients who received these showing a partial response. One tumor with a partial small-cell component showed a partial response to both an etoposide-based regimen and a taxane-based regimen. In urachal cancer, curative surgery is still the recommended treatment with respect to overall survival. A 5-FU-based chemotherapy regimen could be considered for metastatic recurrent disease. © 2014 S. Karger AG, Basel.

  6. Quality of Life in Elderly Cancer Patients Undergoing Chemotherapy.

    Science.gov (United States)

    Lavdaniti, Maria; Zyga, Sofia; Vlachou, Eugenia; Sapountzi-Krepia, Despina

    2017-01-01

    As life expectancy increases, it is expected that 60% of all cases of cancer will be detected in elderly patients in the next two decades. Cancer treatment for older persons is complicated by a number of factors, thus negatively affecting patients' quality of life. The purpose of this study is to investigate quality of life in elderly cancer patients undergoing chemotherapy. This study was descriptive and non-experimental. It was conducted in one large hospital in a major city of Northern Greece. The sample was convenience comprising 53 elderly cancer patients undergoing cycle 3 chemotherapy. The data was collected using the Functional Assessment of Cancer Therapy scale and included questions related to demographic and clinical characteristics. The majority of participants were men (n = 27, 50.9%) who were married (n = 32, 79.5%). Their mean age was 70.07 ± 3.60. Almost half of the sample (n = 30, 56.6%) had colon cancer. There was a statistical significant difference between men and women pertaining to physical wellbeing (p = 0.004) and overall quality of life (p quality of life (p quality of life (p quality of life and its related factors in elderly cancer patients. It is highly recommended to envisage measures for improving quality of life in this group of cancer patients.

  7. Cancer chemotherapy and biotherapy: principles and practice

    National Research Council Canada - National Science Library

    Chabner, Bruce; Longo, Dan L

    2011-01-01

    .... Organized by drug class, the book provides the latest information on all drugs and biological agents--their mechanisms of action, interactions with other agents, toxicities, side effects, and mechanisms of resistance...

  8. Chemotherapy in the treatment of metastatic prostate cancer: the present state of the problem

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2015-01-01

    Full Text Available The paper reviews the current possibilities of cytostatic chemotherapy in patients with metastatic prostate cancer. It gives the data of studies dealing with the early use of docetaxel in patents with hormone-susceptible tumors and analyzes approaches to sequential therapy with docetaxel, cabazitaxel, and antiandrogens (abiraterone, enzalutamide in patients with castration-refractory prostate cancer. Assessment of the prognostic role of different clinical and biological factors could provide an algorithm for the choice of first- and second-line therapy in patients with castration resistance.

  9. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  10. 76 FR 51034 - Availability of Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy...

    Science.gov (United States)

    2011-08-17

    ... Chemotherapy During Pregnancy; Request for Comments; Announcement of a Panel Meeting To Peer Review Draft... of the Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy During Pregnancy... of Cancer Chemotherapy During Pregnancy, which has been prepared by the NTP Office of Health...

  11. Taxane chemotherapy for hormone-naïve prostate cancer with its expanding role as breakthrough strategy

    Directory of Open Access Journals (Sweden)

    Masaki eShiota

    2016-01-01

    Full Text Available Historically, androgen-deprivation therapy was the only primary treatment for metastatic prostate cancer. After prostate cancer develops into castration-resistant prostate cancer, there are a few life-prolonging drugs, including taxanes such as docetaxel and cabazitaxel, as well as novel androgen receptor-targeting agents such as abiraterone acetate and enzalutamide, which have been proved in clinical trials. However, the prognosis of men with castration-resistant prostate cancer is still poor. The duration from initiation of androgen-deprivation therapy to castration-resistant prostate cancer has not improved in recent decades because no novel therapeutic options have emerged. However, recently, up-front docetaxel chemotherapy has been shown to prolong progression-free as well as overall survival in men with metastatic hormone-naïve prostate cancer. This offers a new way to expand the role of chemotherapy for hormone-naïve prostate cancer. In this review, we summarize the proof-of-concept as well as the current status of taxane chemotherapy for hormone-naïve prostate cancer, focusing on phase 3 clinical trials investigating oncological outcome, and discuss the future direction in this field.

  12. Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy

    Science.gov (United States)

    Orlando, Paul A.; Gatenby, Robert A.; Brown, Joel S.

    2012-01-01

    Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors “choose” an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor “chooses” its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients. PMID:23197192

  13. Erlotinib resistance in Lung Cancer: Current Progress and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Joy eTang

    2013-02-01

    Full Text Available Lung cancer is the most common cancer in the world. Despite modern advancements in surgeries, chemotherapies and radiotherapies over the past few years, lung cancer still remains a very difficult disease to treat. This has left the death rate from lung cancer victims largely unchanged throughout the past few decades. A key cause for the high mortality rate is the drug resistance that builds up for patients being currently treated with the chemotherapeutic agents. Although certain chemotherapeutic agents may initially effectively treat lung cancer patients, there is a high probability that there will be a reoccurrence of the cancer after the patient develops resistance to the drug. Erlotinib, the epidermal growth factor receptor (EGFR-targeting tyrosine kinase inhibitor, has been approved for localized as well as metastatic non-small cell lung cancer where it seems to be more effective in patients with EGFR mutations. Resistance to erlotinib is a common observation in clinics and this review details our current knowledge on the subject. We discuss the causes of such resistance as well as innovative research to overcome it. Evidently, new chemotherapy strategies are desperately needed in order to better treat lung cancer patients. Current research is investigating alternative treatment plans to enhance the chemotherapy that is already offered. Better insight into the molecular mechanisms behind combination therapy pathways and even single molecular pathways may help improve the efficacy of the current treatment options.

  14. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    Science.gov (United States)

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I; Fizazi, Karim; Bossi, Alberto; van den Eertwegh, Alfons J M; Krainer, Michael; Houede, Nadine; Santos, Ricardo; Mahammedi, Hakim; Ng, Siobhan; Maio, Michele; Franke, Fabio A; Sundar, Santhanam; Agarwal, Neeraj; Bergman, Andries M; Ciuleanu, Tudor E; Korbenfeld, Ernesto; Sengeløv, Lisa; Hansen, Steinbjorn; Logothetis, Christopher; Beer, Tomasz M; McHenry, M Brent; Gagnier, Paul; Liu, David; Gerritsen, Winald R

    2015-01-01

    Summary Background Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel chemotherapy. Methods We did a multicentre, randomised, double-blind, phase 3 trial in which men with at least one bone metastasis from castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned in a 1:1 ratio to receive bone-directed radiotherapy (8 Gy in one fraction) followed by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Non-progressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by Eastern Cooperative Oncology Group performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. The primary endpoint was overall survival, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00861614. Findings From May 26, 2009, to Feb 15, 2012, 799 patients were randomly assigned (399 to ipilimumab and 400 to placebo), all of whom were included in the intention-to-treat analysis. Median overall survival was 11·2 months (95% CI 9·5–12·7) with ipilimumab and 10·0 months (8·3–11·0) with placebo (hazard ratio [HR] 0·85, 0·72–1·00; p=0·053). However, the assessment of the proportional hazards assumption showed that it was violated (p=0·0031). A piecewise hazard model showed that the HR changed over time: the HR for 0–5 months was 1·46 (95% CI 1·10–1·95), for 5–12 months was 0·65 (0·50–0·85), and

  15. The impact of cisplat based chemotherapy on advanced ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Prasad G

    1995-10-01

    Full Text Available Cisplatinum based chemotherapy has become the standard treatment for ovarian cancers due to its proved superiority over non-cisplat based regimes. However, the therapeutic impact of cisplat based regimes compared to cheaper non-cisplatinum based regimes is questionable when multiple variables such as residual disease, histologic type, grade are introduced. This report is a study of 110 Stage III ovarian cancer patients from 1985-89, with cisplat (n = 69 and non cisplat (n = 41 based chemotherapy. The results of both regimes with reference to the multiple variable factors are presented. We conclude that cisplat based regimes appear to be superior to non-cisplat based regimes except probably in poorly differentiated ovarian tumors where the results were similar with either regimen.

  16. Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

    Science.gov (United States)

    Gerber, David E.; Schiller, Joan H.

    2013-01-01

    Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

  17. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  18. Motor Performance following Chemotherapy for Childhood Cancer

    NARCIS (Netherlands)

    J.E.M. Hartman (Annelies)

    2009-01-01

    textabstractMalignancies are the second most frequent cause of death in children in the Netherlands. Every year approximately 500-600 children aged 0-18 years are diagnosed with cancer 1. Survival rates of children with malignancies have increased tremendously, particularly in the last decennium.

  19. Response to influenza virus vaccination during chemotherapy in patients with breast cancer

    NARCIS (Netherlands)

    Meerveld-Eggink, A.; de Weerdt, O.; van der Velden, A. M. T.; Los, M.; van der Velden, A. W. G.; Stouthard, J. M. L.; Nijziel, M. R.; Westerman, M.; Beeker, A.; van Beek, R.; Rimmelzwaan, G. F.; Rijkers, G. T.; Biesma, D. H.

    Background: Patients receiving chemotherapy are at increased risk for influenza virus infection. Little is known about the preferred moment of vaccination during chemotherapy. Patients and methods: Breast cancer patients received influenza vaccination during FEC (5-fluorouracil, epirubicin and

  20. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval debulking...

  1. Re-evaluating the cost of outpatient cancer chemotherapy.

    OpenAIRE

    Wodinsky, H. B.; DeAngelis, C.; Rusthoven, J J; Kerr, I G; Sutherland, D.; Iscoe, N; Buckman, R.; Kornijenko, M

    1987-01-01

    Chemotherapy for common malignant tumours has historically been considered relatively expensive. An examination of costs at the Toronto-Bayview Regional Cancer Centre and Sunnybrook Medical Centre, Toronto, suggests that this perception is not accurate. The cost of chemotherapeutic agents administered on an outpatient basis over 4 to 6 months in established drug protocols ranged from $260 to $5374 (mean $2224). The total cost of outpatient administration was estimated to be $152.53 per dose, ...

  2. Mechanisms of resistance in castration-resistant prostate cancer (CRPC).

    Science.gov (United States)

    Chandrasekar, Thenappan; Yang, Joy C; Gao, Allen C; Evans, Christopher P

    2015-06-01

    Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies.

  3. Motor Performance following Chemotherapy for Childhood Cancer

    OpenAIRE

    Hartman, Annelies

    2009-01-01

    textabstractMalignancies are the second most frequent cause of death in children in the Netherlands. Every year approximately 500-600 children aged 0-18 years are diagnosed with cancer 1. Survival rates of children with malignancies have increased tremendously, particularly in the last decennium. The survival rate of children with acute lymphatic leukemia (ALL) for example, has risen to almost 85% 2. One of the reasons for the increase in survival has been stepwise improvement in combination ...

  4. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    With long-term follow-up, the DBCG 77B trial demonstrates that oral single-agent cyclophosphamide significantly reduces the risk of recurrence and mortality as compared with no systemic therapy in pre-menopausal patients with high-risk early breast cancer. DBCG 77B is the only randomised trial...... not was superior to classic CMF. A further reduction in breast cancer mortality appeared in the EBCTCG meta-analysis from the addition of a taxane to a standard AC, while the substitution of cycles or drugs with a taxane was not associated with a reduction in mortality. No apparent benefit was observed in an early...... analysis of the DBCG 82C evaluating the addition of CMF to tamoxifen in post-menopausal high-risk breast cancer patients. Apart from menopausal status, the two trials had identical selection criteria, and the differences in outcome warranted a long-term follow-up of the 82C trial. After ten years of follow...

  5. Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy

    Science.gov (United States)

    Dasgupta, Anindya; Shields, Jordan E.

    2012-01-01

    Abstract Multimodal therapy approaches, such as combining chemotherapy agents with cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector cells. Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches. PMID:22397715

  6. Efficacy of Scalp Cooling in Preventing Chemotherapy-Induced Alopecia in Breast Cancer Patients Receiving Adjuvant Docetaxel and Cyclophosphamide Chemotherapy.

    Science.gov (United States)

    Cigler, Tessa; Isseroff, Devora; Fiederlein, Barbara; Schneider, Sarah; Chuang, Ellen; Vahdat, Linda; Moore, Anne

    2015-10-01

    Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of many chemotherapy agents. The TC (docetaxel [Taxotere] and cyclophosphamide) chemotherapy regimen is typically associated with complete alopecia. Scalp cooling with cold caps has been reported to minimize or prevent CIA. We conducted a prospective study to assess efficacy of scalp cooling in preventing CIA among women receiving adjuvant TC chemotherapy for breast cancer. Women at the Weill Cornell Breast Center who independently elected to use scalp cooling with cold caps during adjuvant TC chemotherapy were asked to participate. Degree of hair loss was assessed by a single practitioner using Dean's alopecia scale (grade 1/excellent [ 75% hair loss]), by digital photographs, and by patient self-report of hair thinning or the need to wear a wig/head covering, or both. Assessments were made before each chemotherapy treatment and at follow-up visits between 3 weeks and 3 months after completion of chemotherapy. Of 20 evaluable patients, 10% reported a need to wear a wig/head covering at the follow-up visit. Dean's alopecia score was excellent for 65% of patients, good for 25% of patients, and moderate or poor for 10% of patients. The majority of patients reported hair thinning after every chemotherapy cycle. No patient discontinued therapy because of an intolerance to cold caps. Scalp cooling with cold caps appears to be effective in preventing CIA among the majority of women undergoing treatment with TC chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Association between the ERCC1 polymorphism and platinum-based chemotherapy effectiveness in ovarian cancer: a meta-analysis.

    Science.gov (United States)

    Tang, Ning; Lyu, Dan; Zhang, Yan; Liu, Haiping

    2017-06-17

    Ovarian cancer is a prominent public health problem which affects people all around the world. Platinum-based chemotherapy is a common treatment for ovarian cancer, however, the effectiveness of chemotherapy varies from patient to patient. The excision repair cross complementation group 1 (ERCC1) protein may mediate chemotherapy resistance. A meta-analysis was conducted to explore whether platinum-based chemotherapy effectiveness could be attributed to the ERCC1 C19007T polymorphisms. Seven major databases (EMBASE, Web of Science, Pubmed, Springer Link, Chinese National Knowledge Infrastructure (CNKI), EBSCO and Science Direct databases) were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the results. In this meta-analysis, 1169 subjects (425 non-responders and 744 responders) from 8 studies were included. The overall OR (C vs. T alleles) using random model was 1.07 (95% CI 0.75-1.52, P = 0.7), which was not statistically significant. Moreover, there was no significant difference in the analysis by race. There is no association between the ERCC1 C19007T polymorphism and platinum-based chemotherapy effectiveness in ovarian cancer. The polymorphism did not have a significant impact on platinum-based chemotherapy in non-responders and responders.

  8. Chemotherapy for gastric cancer patients - time for personalization in medicine?

    Science.gov (United States)

    Nowara, Elżbieta; Boratyn-Nowicka, Agnieszka; Polakiewicz-Gilowska, Anna; Drosik, Anna; Kustra, Magdalena; Huszno, Joanna

    2012-01-01

    Gastric cancer is one of the most frequent neoplasms. Although the incidence of gastric cancer worldwide has declined, there is still high mortality. Treatment of inoperable disease is under evaluation in clinical trials. In palliative treatment chemotherapy containing cisplatin and 5-fluorouracil is the most widely used. In the past years progress in tumour biology has advanced greatly and has led to development of new molecules aimed at targets important for cancer expansion. There are several randomized trials under targeted therapies for gastric cancer patients. One of them led to approval of trastuzumab. In the current paper the authors illustrate new possibilities in systemic treatment with particular attention to targeted therapy and personalization in medicine.

  9. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  10. Research Progress on Natural Triterpenoid Saponins in the Chemoprevention and Chemotherapy of Cancer.

    Science.gov (United States)

    Du, Jun-Rong; Long, Fang-Yi; Chen, Chu

    2014-01-01

    Triterpenoid saponins are glycosides with remarkable structural and bioactive diversity. They are becoming increasingly significant in the treatment of cancer due to their efficacy and safety. This chapter provides an update on the sources, pharmacological effects, structure-activity relationships, and clinical studies of anticancer triterpenoid saponins with a particular focus on the molecular mechanisms underlying their therapeutic properties. The correlative references and study reports described were collected through PubMed. The anticancer triterpenoid saponins enable the inhibition of cancer formation and progression by modulating multiple signaling targets related to cellular proliferation, apoptosis, autophagy, metastasis, angiogenesis, inflammation, oxidative stress, multidrug resistance, cancer stem cells, and microRNAs. This review provides new insights into the molecular basis of triterpenoid saponins in the chemoprevention and chemotherapy of cancer. © 2014 Elsevier Inc. All rights reserved.

  11. Genotyping panel for assessing response to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Hampel Heather

    2008-06-01

    Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

  12. Predictors of hope among women with breast cancer during chemotherapy

    Directory of Open Access Journals (Sweden)

    Alessandra Cristina Sartore Balsanelli

    Full Text Available Abstract OBJECTIVE Identifying the predictors of hope in patients with breast cancer during chemotherapy treatment. METHOD A prospective longitudinal study. The sample was composed of 122 women who responded to the instruments of hope, anxiety and depression, coping, fatigue, religiosity and self-esteem in the first and last cycle of chemotherapy. These variables were used in adjusting the logistic regression model that characterized multivariate statistics, allowing identification of predictor variables. RESULT The increase of hope at the end of chemotherapy treatment was statistically significant (p = 0.012. The delay in undergoing treatment from the onset of breast cancer symptoms, Karnofsky Performance Status, depression, self-esteem and pain were characterized as factors being associated to hope by univariate analysis. Among the variables analyzed, pain was the only predicting factor of hope. CONCLUSION Pain was the predicting factor in this sample. Hope increased during treatment and revealed the following associated factors: Karnofsky Performance Status, delay in starting the treatment, depression, self-esteem and pain. This study brought forth a multidisciplinary contribution, allowing for understanding the factors that can influence hope and presenting support to nursing care. The data evidenced conditions of improvement or worsening of hope, which requires interdisciplinary attention in Oncology.

  13. Synthetic lethality to overcome cancer drug resistance.

    Science.gov (United States)

    Porcelli, L; Quatrale, A E; Mantuano, P; Silvestris, N; Brunetti, A E; Calvert, H; Paradiso, A; Azzariti, A

    2012-01-01

    A large body of evidence point out that the onset of synthetic lethality may provide a useful tool for amplifying the efficacy of drugs in anticancer regimens, to uncover interdependence between genes and to identify predictive factors that would be extremely useful to guide in the selection of more effective targeted drugs and drug combinations for each patient. Here, we provide an overview on the exploitation of synthetic lethality to overcome drug resistance to conventional chemotherapy in several types of solid tumors. We report recent findings on cellular markers and gene mutations which are specifically essential for the viability of cancer cells and for resistance to chemotherapeutics. In addition, new molecularly targeted strategies to overcome drug resistance are suggested.

  14. Nutritional problems among patients affected by cancer during chemotherapy

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2016-01-01

    Full Text Available Chemotherapy is one of the primary methods of treating cancer. Symptoms occurring during this form of therapy affect patients’ general health status, cause malnutrition, and deteriorate the quality of life of oncology patients, which results in cachexia. Malnutrition during treatment and the resulting bad general health status of patients may lead to disqualification from chemotherapy treatment. Cachexia is a complex and multi-factorial process, characterised by the nearly unknown mechanism of its development. What is extremely crucial is the evaluation of the state of malnutrition among patients qualified for cytostatic therapy and regular control of this state during therapy and immediately after its termination. Clinical practice indicates the importance of applying pharmacotherapy, nutritional treatment, and targeted education for the patient and their closest family regarding diet and correct behaviour, which significantly reduces anxiety and stress.

  15. Re-evaluating the cost of outpatient cancer chemotherapy.

    Science.gov (United States)

    Wodinsky, H B; DeAngelis, C; Rusthoven, J J; Kerr, I G; Sutherland, D; Iscoe, N; Buckman, R; Kornijenko, M

    1987-11-15

    Chemotherapy for common malignant tumours has historically been considered relatively expensive. An examination of costs at the Toronto-Bayview Regional Cancer Centre and Sunnybrook Medical Centre, Toronto, suggests that this perception is not accurate. The cost of chemotherapeutic agents administered on an outpatient basis over 4 to 6 months in established drug protocols ranged from $260 to $5374 (mean $2224). The total cost of outpatient administration was estimated to be $152.53 per dose, compared with $185.39 for inpatient administration of the same protocol, a difference of 22%. The difference was predominantly due to a higher allocated per-diem charge at the medical centre. The results indicate that outpatient administration reduces the overall cost of chemotherapy.

  16. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  17. A rehabilitation program for lung cancer patients during postthoracotomy chemotherapy.

    Science.gov (United States)

    Hoffman, Amy J; Brintnall, Ruth Ann; von Eye, Alexander; Jones, Lee W; Alderink, Gordon; Patzelt, Lawrence H; Brown, Jean K

    2014-01-01

    The objective of this pilot study was to describe the effects of a 16-week home-based rehabilitative exercise program on cancer-related fatigue (CRF), other symptoms, functional status, and quality of life (QOL) for patients with non-small cell lung cancer (NSCLC) after thoracotomy starting within days after hospital discharge and continuing through the initiation and completion of chemotherapy. Five patients with NSCLC completed the Brief Fatigue Inventory (measuring CRF severity) and the MD Anderson Symptom Inventory (measuring symptom severity) before and after thoractomy, and at the end of each week of the 16-week exercise program. Additionally, the Medical Outcomes Study Short Form-36 (measuring physical and mental functional status) and the Quality of Life Index (measuring QOL) were completed before and after thoracotomy, after weeks 3, 6, 12, and 16 (the end of the exercise program). Further, the 6-minute walk test (measuring functional capacity) was administered before thoracotomy, prior to the initiation of chemotherapy and/or radiation therapy, and at the end of the 16-week exercise program, after completion of chemotherapy. Participants had a mean age of 63 years and a mean of five comorbid conditions; the exercise program was initiated within 4 days after hospital discharge. Participants' CRF severity scores were reduced to mild levels, while the mean number of symptoms decreased from 9 postthoracotomy to 6 after the exercise program, with mean levels of severity and interference decreasing to below prethoracotomy levels. Likewise, participants' functional status and QOL after completing the exercise program improved to near or above prethoracotomy levels. The home-based, light-intensity exercise program for NSCLC patients receiving and completing adjuvant chemotherapy postthoracotomy showed promising trends in improving CRF severity, other symptom severity, functional status, and QOL. Further testing via a two-arm randomized controlled trial is being

  18. Oral cancer: Current role of radiotherapy and chemotherapy.

    Science.gov (United States)

    Huang, Shao-Hui; O'Sullivan, Brian

    2013-03-01

    The term oral cavity cancer (OSCC) constitutes cancers of the mucosal surfaces of the lips, floor of mouth, oral tongue, buccal mucosa, lower and upper gingiva, hard palate and retromolar trigone. Treatment approaches for OSCC include single management with surgery, radiotherapy [external beam radiotherapy (EBRT) and/or brachytherapy], as well as adjuvant systemic therapy (chemotherapy and/or target agents); various combinations of these modalities may also be used depending on the disease presentation and pathological findings. The selection of sole or combined modality is based on various considerations that include disease control probability, the anticipated functional and cosmetic outcomes, tumor resectability, patient general condition, and availability of resources and expertise. For resectable OSCC, the mainstay of treatment is surgery, though same practitioners may advocate for the use of radiotherapy alone in selected "early" disease presentations or combined with chemotherapy in more locally advanced stage disease. In general, the latter is more commonly reserved for cases where surgery may be problematic. Thus, primary radiotherapy ± chemotherapy is usually reserved for patients unable to tolerate or who are otherwise unsuited for surgery. On the other hand, brachytherapy may be considered as a sole modality for early small primary tumor. It also has a role as an adjuvant to surgery in the setting of inadequate pathologically assessed resection margins, as does postoperative external beam radiotherapy ± chemotherapy, which is usually reserved for those with unfavorable pathological features. Brachytherapy can also be especially useful in the re-irradiation setting for persistent or recurrent disease or for a second primary arising within a previous radiation field. Biological agents targeting the epithelial growth factor receptor (EGFR) have emerged as a potential modality in combination with radiotherapy or chemoradiotherapy and are currently under

  19. [Cancer related fatigue in patients with breast cancer after chemotherapy and coping style].

    Science.gov (United States)

    Jiang, Pinglan; Wang, Shuhong; Jiang, Dongmei; Yu, Lingli

    2011-04-01

    To study the relevance between cancer related fatigue and coping styles in breast cancer patients after chemotherapy. A survey was conducted in 396 patients with breast cancer after chemotherapy on cancer related fatigue scale and Jalowiec coping scale, and the relation was analyzed. The rate of overall fatigue in breast cancer patients was 96.97%, mostly moderate fatigue. The rate of fatigue dimensions from high to low was physical fatigue, feeling fatigue and cognitive fatigue, respectively. The score of coping styles in patients with breast cancer after chemotherapy from high to low was optimistic coping, facing bravely, support seeking, self-reliance, emotional catharsis, avoidance, fatalism, and conservation. The most widely used coping style was optimistic coping style, and the least was emotional catharisis. There was a positive correlation between coping style of emotional catharsis and cancer related fatigue of all dimensions (Pcancer related fatigue in patients with breast cancer after chemotherapy. We should guide the patients to more active coping styles, to enhance the ability of psychological adaption in patients, reduce cancer related fatigue, and improve the quality of life.

  20. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I

    2014-01-01

    BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel c...

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

    NARCIS (Netherlands)

    Saad, F.; Shore, N.; Poppel, H. Van; Rathkopf, D.E.; Smith, M.R.; Bono, J.S. de; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mulders, P.F.A.; Mainwaring, P.; Hainsworth, J.D.; Beer, T.M.; North, S.; Fradet, Y.; Griffin, T.A.; Porre, P. De; Londhe, A.; Kheoh, T.; Small, E.J.; Scher, H.I.; Molina, A.; Ryan, C.J.

    2015-01-01

    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

  2. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    NARCIS (Netherlands)

    Kwon, E.D.; Drake, C.G.; Scher, H.I.; Fizazi, K.; Bossi, A.; Eertwegh, A.J. van den; Krainer, M.; Houede, N.; Santos, R.; Mahammedi, H.; Ng, S.; Maio, M.; Franke, F.A.; Sundar, S.; Agarwal, N.; Bergman, A.M.; Ciuleanu, T.E.; Korbenfeld, E.; Sengelov, L.; Hansen, S.; Logothetis, C.; Beer, T.M.; McHenry, M.B.; Gagnier, P.; Liu, D.; Gerritsen, W.R.

    2014-01-01

    BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel

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

    Science.gov (United States)

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

    2015-02-01

    There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications. Copyright © 2014 The Royal College of Radiologists. Published by

  4. Genetic Effect of Chemotherapy Exposure in Children of Testicular Cancer Survivors

    National Research Council Canada - National Science Library

    Kryukov, Gregory V; Bielski, Craig M; Samocha, Kaitlin; Fromer, Menachem; Seepo, Sara; Gentry, Carleen; Neale, Benjamin; Garraway, Levi A; Sweeney, Christopher J; Taplin, Mary-Ellen; Van Allen, Eliezer M

    2016-01-01

    .... Epidemiologic studies have not demonstrated a significant increase in congenital abnormalities in posttreatment children of cancer survivors, but the inherited genome-wide effect of chemotherapy...

  5. A rehabilitation program for lung cancer patients during postthoracotomy chemotherapy

    Directory of Open Access Journals (Sweden)

    Hoffman AJ

    2014-03-01

    Full Text Available Amy J Hoffman,1 Ruth Ann Brintnall,2 Alexander von Eye,3 Lee W Jones,4 Gordon Alderink,5 Lawrence H Patzelt,6 Jean K Brown7 1College of Nursing, Michigan State University, East Lansing, MI, USA; 2Kirkhof College of Nursing, Grand Valley State University, Grand Rapids, MI, USA; 3Psychology Department, Michigan State University, East Lansing, MI, USA; 4Duke Center for Cancer Survivorship Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA; 5Frederik Meijer Honors College, Grand Valley State University, Grand Rapids, MI, USA; 6Spectrum Health, Grand Rapids, MI, USA and College of Human Medicine, Michigan State University, East Lansing, MI, USA; 7School of Nursing, University at Buffalo, the State University of New York, Buffalo, NY, USA Objective: The objective of this pilot study was to describe the effects of a 16-week home-based rehabilitative exercise program on cancer-related fatigue (CRF, other symptoms, functional status, and quality of life (QOL for patients with non-small cell lung cancer (NSCLC after thoracotomy starting within days after hospital discharge and continuing through the initiation and completion of chemotherapy. Materials and methods: Five patients with NSCLC completed the Brief Fatigue Inventory (measuring CRF severity and the MD Anderson Symptom Inventory (measuring symptom severity before and after thoractomy, and at the end of each week of the 16-week exercise program. Additionally, the Medical Outcomes Study Short Form-36 (measuring physical and mental functional status and the Quality of Life Index (measuring QOL were completed before and after thoracotomy, after weeks 3, 6, 12, and 16 (the end of the exercise program. Further, the 6-minute walk test (measuring functional capacity was administered before thoracotomy, prior to the initiation of chemotherapy and/or radiation therapy, and at the end of the 16-week exercise program, after completion of chemotherapy. Results: Participants had a

  6. A systematic review of genes involved in the inverse resistance relationship between cisplatin and paclitaxel chemotherapy: role of BRCA1.

    Science.gov (United States)

    Stordal, Britta; Davey, Ross

    2009-05-01

    A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel. Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as act as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.

  7. Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

    NARCIS (Netherlands)

    Lawrie, Theresa A.; Winter-Roach, Brett A.; Heus, Pauline; Kitchener, Henry C.

    2015-01-01

    OBJECTIVES: To undertake a systematic review of the evidence for adjuvant chemotherapy in early-stage epithelial ovarian cancer to determine whether chemotherapy following surgery offers a survival advantage over the policy of observation following surgery (with chemotherapy reserved for treatment

  8. Diffuse optical methods for assessing breast cancer chemotherapy

    Science.gov (United States)

    Tromberg, Bruce J.

    2014-03-01

    In his talk, "Diffuse Optical Methods for Assessing Breast Cancer Chemotherapy," SPIE Fellow Bruce Tromberg (Beckman Laser Institute and Medical Clinic) describes a method combining frequency domain photon migration, essentially a method of tracking photon motion in tissue, with a NIR spectroscopy technique using 850nm LEDs. The result is a scatter corrected absorption spectra. The technique takes advantage of elevated blood and water levels and decreased lipid levels in the presence of tumors to provide a more accurate mapping of the breast, allowing more effective treatment. Tromberg's team recently completed their first full mapping of the breast and have taken the instrument from a standalone unit to a portable one suitable for travel. In addition to providing feedback to enhance breast cancer treatment, Tromberg expects that this technique will be applicable in treating other forms of cancer as well.

  9. [Cognitive function in breast cancer patients on chemotherapy: a longitudinal study].

    Science.gov (United States)

    Chen, Xingui; Li, Jingjing; Zhu, Chunyan; Li, Dandan; Zhang, Jingjie; Wang, Kai

    2014-01-07

    To explore whether cognitive impairment in breast cancer patients after the completion of chemotherapy treatment in comparisons with breast cancer patients without chemotherapy treatment and matched healthy controls. A neuropsychology battery was applied in all breast cancer patients at our hospital from January 2012 to February 2013. Forty-two breast cancer patients with chemotherapy treatment (CT) underwent neuropsychologic testing before the start of chemotherapy (T1) and after treatment (T2). And 37 patients without chemotherapy treatment (non-CT) and matched healthy controls (HC) underwent the same assessment at matched intervals. The CT group performed significantly worse on attention, memory and executive function tests at T2 versus T1 (P Stroop test B and Stroop test C were longer in the CT group (P cancer patients on Chemotherapy.

  10. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Science.gov (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  11. Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Kari T. Syvänen

    2014-05-01

    Full Text Available Neoadjuvant chemotherapy (NAC in muscle-invasive bladder cancer was introduced several years ago. Despite the evidence supporting its use in clinical practice, only a minority of patients who undergo radical cystectomy receive preoperative chemotherapy. In addition, recommendations and methods to detect patients who would benefit the most from NAC are still unclear. The European Association of Urology (EAU guidelines panel on muscle-invasive and metastatic bladder cancer recommends the use of cisplatin-based NAC for T2-T4a, cN0 M0 bladder cancer if the patient has a performance status ≥2 and if the renal function is not impaired, but the American Urological Association, for example, does not have any guideline recommendations on this topic at all. In this review we describe the current literature supporting NAC in association with radical cystectomy in muscle-invasive urothelial carcinoma of the bladder. Evidence acquisition was made searching the Medline database for original articles published before 1st February 2014, with search terms: “neoadjuvant chemotherapy”, “radical cystectomy”, and “invasive bladder cancer”.

  12. Dual Role of Mitophagy in Cancer Drug Resistance.

    Science.gov (United States)

    Yan, Chen; Li, Tao-Sheng

    2018-02-01

    The effectiveness of chemotherapy is largely limited by drug resistance. In the past few decades, modulation of anticancer drug resistance plays little role in benefit of clinical outcomes due to complex drug resistance mechanisms. Mitophagy, an important mitochondrial quality control system, selectively degrades excessive or damaged mitochondria by autophagy. Accumulating reports are suggesting that dysregulation of mitophagy contributes to neoplastic progression and drug resistance in various types of tumors. Mitophagy was originally thought to be an onco-suppressor that maintains cellular homeostasis and prevents oncogenic transformation. On the other hand, mitophagy promotes cancer cell survival under cytotoxic stress by degrading damaged mitochondria and reducing mitochondrial reactive oxygen species. Therefore, induction and inhibition of mitophagy in cancer drug resistance are controversial. In this review, we summarize current knowledge on the dual role of mitophagy in cancer drug resistance. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  13. Small cell carcinoma of vulva. Curative multimodal treatment in face of resistance to initial standard chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Eckert, Franziska; Bamberg, Michael; Mueller, Arndt-Christian [Dept. of Radiooncology, Eberhard Karls Univ. of Tuebingen (Germany); Fehm, Tanja [Gynecologic Clinic, Eberhard Karls Univ. of Tuebingen (Germany)

    2010-09-15

    Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC. (orig.)

  14. Chemotherapy in Non-Small Cell Lung Cancer Patients Receiving Oxygen Therapy.

    Science.gov (United States)

    Watanabe, Keisuke; Shinkai, Masaharu; Tei, Yoshitaka; Kaneko, Takeshi

    2016-01-01

    Information regarding chemotherapy in non-small cell lung cancer (NSCLC) patients with chronic respiratory failure is limited. We retrospectively analyzed patients who received oxygen therapy and underwent chemotherapy for NSCLC at our hospital. 6 patients with NSCLC receiving oxygen therapy (4 with unresectable lung cancer and 2 with postoperative recurrent lung cancer) underwent chemotherapy. 1 patient achieved a partial response and 1 achieved stable disease after first-line chemotherapy. The median overall survival (OS) was 247 days in all patients. Patients with unresectable NSCLC and recurrent NSCLC had median OS times of 282 and 239 days, respectively. Grade 3 lung infection occurred in 4 patients during chemotherapy treatment; however, there were no chemotherapy-related deaths. There is a possibility that chemotherapy could improve the survival of NSCLC patients who receive oxygen therapy. © 2016 S. Karger GmbH, Freiburg.

  15. Chemotherapy

    Science.gov (United States)

    ... the cancer. If you know someone who has cancer, the person will appreciate your phone calls, email messages, cards, letters, and visits. Let the person know you care and still want to spend time together. It is important to remember that cancer is not contagious — you cannot catch it from ...

  16. Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival.

    Science.gov (United States)

    Kim, Roger H; Kavanaugh, Mindie M; Caldito, Gloria C

    2017-06-01

    Laparoscopic surgery for colon cancer has been demonstrated in clinical trials to have short-term benefits when compared to the open surgical approach. Guidelines of the National Comprehensive Cancer Network recommend that patients with stage III or high-risk stage II colon cancer undergo adjuvant chemotherapy. We hypothesized that laparoscopic colectomy is associated with increased compliance to recommendations for chemotherapy, a lesser time to start of chemotherapy, and increased overall survival. The National Cancer Data Base was queried to identify patients with stage III or high-risk stage II colon cancer (T4, positive margins, chemotherapy, time from diagnosis and date of operation to start of chemotherapy, and overall survival were compared. A total of 48,257 patients were included for analysis; 18,801 patients underwent laparoscopic colectomy and 29,456 underwent open colectomy. Laparoscopic colectomy patients received adjuvant chemotherapy at a somewhat greater rate than open colectomy (66.2% vs 59.4%, P chemotherapy, mean time to start of chemotherapy after definitive resection was somewhat less for laparoscopic colectomy than open colectomy (48.7 vs 52.7 days, P chemotherapy for stage III and high-risk stage II colon cancer, as well as a slightly lesser time to start of chemotherapy and improved overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?

    NARCIS (Netherlands)

    Borst, Piet

    2012-01-01

    Although chemotherapy of tumours has scored successes, drug resistance remains the major cause of death of cancer patients. Initial treatment often leaves residual disease, from which the tumour regrows. Eventually, most tumours become resistant to all available chemotherapy. I call this

  18. Symptom incidence, distress, cancer-related distress, and adherence to chemotherapy among African American women with breast cancer.

    Science.gov (United States)

    Yee, Melissa K; Sereika, Susan M; Bender, Catherine M; Brufsky, Adam M; Connolly, Mary C; Rosenzweig, Margaret Q

    2017-06-01

    There is a persistent racial survival disparity between African American (AA) and white women with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The purpose of the current study was to: 1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and 2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe. Descriptive, comparative, and correlational analyses of symptom incidence, symptom distress, cancer-related distress, and prescribed chemotherapy dose received among a cohort of AA women receiving chemotherapy for breast cancer were performed. AA women (121 women) experienced worsening symptoms from baseline to midpoint in chemotherapy and then stabilized for the duration of therapy. The inability to receive 85% of the prescribed chemotherapy within a prescribed time point was found to be significantly correlated with midpoint symptom distress. The main findings of the current study were that AA women experience a deterioration in symptom distress over the course of chemotherapy from baseline (before chemotherapy) to the midpoint, which was found to be associated with less adherence to chemotherapy overall. Thus, the incidence and management of physical and emotional symptoms, as measured through a multidimensional symptom measurement tool, may be contributing to breast cancer dose disparity and should be explored further. Cancer 2017;123:2061-2069. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?

    Science.gov (United States)

    Bertocchi, Paola; Aroldi, Francesca; Prochilo, Tiziana; Meriggi, Fausto; Beretta, Giordano Domenico; Zaniboni, Alberto

    2017-04-01

    The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib. We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival. Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%. Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib

  20. Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage III colon cancer

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Christensen, Ib Jarle; Sölétormos, György

    2010-01-01

    Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antige...... (CEA) levels in patients with stage III colon cancer.......Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen...

  1. Maximum physical capacity testing in cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Knutsen, L.; Quist, M; Midtgaard, J

    2006-01-01

    BACKGROUND: Over the past few years there has been a growing interest in the field of physical exercise in rehabilitation of cancer patients, leading to requirements for objective maximum physical capacity measurement (maximum oxygen uptake (VO(2max)) and one-repetition maximum (1RM)) to determine...... dose-response levels in different cancer diagnoses. AIM: To explore the patients' experiences of maximum physical capacity testing while concurrently undergoing chemotherapy and participating in a 6-week, 9 h weekly multidimensional exercise program. DESIGN AND METHOD: Prospective, exploratory study...... in performing maximum physical capacity tests as these motivated them through self-perceived competitiveness and set a standard that served to encourage peak performance. CONCLUSION: The positive attitudes in this sample towards maximum physical capacity open the possibility of introducing physical testing...

  2. Chemotherapy (For Parents)

    Science.gov (United States)

    ... February 2014 More on this topic for: Parents Kids Teens Cancer Center Side Effects of Chemotherapy and Radiation ... Center Chemotherapy Radiation Therapy Some Kinds of Cancer Kids Get Types of Cancer Teens Get Radiation Therapy Chemotherapy Cancer Center Dealing With ...

  3. ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy.

    Science.gov (United States)

    Hida, Kyoko; Kikuchi, Hiroshi; Maishi, Nako; Hida, Yasuhiro

    2017-08-01

    Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called "metronomic chemotherapy". Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters. Copyright © 2017. Published by Elsevier B.V.

  4. Platinum resistance in breast and ovarian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Eckstein Niels

    2011-10-01

    Full Text Available Abstract Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade.

  5. Platinum resistance in breast and ovarian cancer cell lines.

    Science.gov (United States)

    Eckstein, Niels

    2011-10-04

    Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade.

  6. Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.

    Science.gov (United States)

    Shi, Ying; Huang, Xiao-Xiao; Chen, Guo-Bin; Wang, Ying; Zhi, Qiang; Liu, Yuan-Sheng; Wu, Xiao-Ling; Wang, Li-Fen; Yang, Bing; Xiao, Chuan-Xing; Xing, Hui-Qin; Ren, Jian-Lin; Xia, Yin; Guleng, Bayasi

    2016-07-26

    Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.

  7. Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy

    Science.gov (United States)

    Leguisamo, Natalia M.; Gloria, Helena C.; Kalil, Antonio N.; Martins, Talita V.; Azambuja, Daniel B.

    2017-01-01

    Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients’ clinical and pathological features. In addition, we exploited the possible mechanisms underlying the association between altered DNA repair, metabolism and response to chemotherapy. Seventy pairs of sporadic colorectal tumour samples and adjacent non-tumour mucosal specimens were assessed for BER and MMR gene and protein expression and their association with pathological and clinical features. MMR-deficient colon cancer cells (HCT116) transiently overexpressing MPG or XRCC1 were treated with 5-FU or TMZ and evaluated for viability and metabolic intermediate levels. Increase in BER gene and protein expression is associated with more aggressive tumour features and poor pathological outcomes in CRC. However, tumours with reduced MMR gene expression also displayed low MPG, OGG1 and PARP1 expression. Imbalancing BER by overexpression of MPG, but not XRCC1, sensitises MMR-deficient colon cancer cells to 5-FU and TMZ and leads to ATP depletion and lactate accumulation. MPG overexpression alters DNA repair and metabolism and is a potential strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC. PMID:28903334

  8. Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response.

    Science.gov (United States)

    Litviakov, Nicolay V; Cherdyntseva, Nadezhda V; Tsyganov, Matvey M; Denisov, Evgeny V; Garbukov, Evgeny Y; Merzliakova, Marina K; Volkomorov, Victor V; Vtorushin, Sergey V; Zavyalova, Marina V; Slonimskaya, Elena M; Perelmuter, Vladimir M

    2013-01-01

    We aimed to examine the association between alterations in multidrug resistance (MDR) gene expression, measured before and after neoadjuvant chemotherapy (NAC), and short-term response in a cohort of stage IIA-IIIC breast cancer patients (n = 84). All patients were treated with two to four preoperative cycles of FAC (5-fluorouracil-adriamycin-cyclophosphamide), CAX (cyclophosphamide-adriamycin-xeloda) or taxane regimes. The expression levels of key MDR genes (ABCB1, ABCC1, ABCC2, ABCC3, ABCC5, ABCG1, ABCG2, GSTP1, and MVP) were evaluated in both tumor tissues obtained pre-therapy and in specimens removed by final surgery, using TaqMan-based quantitative reverse transcriptase PCR. No significant difference in the average level of MDR gene expression in paired breast tumors before and after NAC was found when analyzed in both responsive and non-responsive patients. There was no correlation between the expression levels of MDR genes in pre-NAC tumors and immediate NAC response. In the group with tumor responses, we found a statistically significant downregulation of expression of ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2, GSTP1, and MVP genes following NAC in FAC and CAX-treated patients (67-93% of cases). In contrast, we found that expression of these genes was upregulated after NAC, mostly in non-responsive patients (55-96% of cases). Responsiveness to taxotere was related to reduced levels of ABCB1, ABCC2, ABCG1, ABCG2, and MVP mRNA in tumor samples collected after chemotherapy. Our results suggest that reductions in MDR gene expression in post-NAC samples in comparison with pre-NAC are associated with tumor response to FAC and CAX as well as taxotere-based NAC, while patients displaying MDR gene upregulation had resistance to therapy.

  9. Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival.

    Science.gov (United States)

    Day, A R; Middleton, G; Smith, R V P; Jourdan, I C; Rockall, T A

    2014-05-01

    Multicentre randomized trials have demonstrated equivalent long-term outcomes for open and laparoscopic resection of colon cancer. Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection. Patients who receive adjuvant chemotherapy in improved survival. Data were collated for patients having an elective laparoscopic or open resection for non-metastatic colorectal cancer between October 2003 and December 2010 and subsequently having adjuvant chemotherapy. Survival analysis was conducted. In all, 209 patients received adjuvant chemotherapy following open (n = 76) or laparoscopic (n = 133) surgery. Median length of stay was 3 days with laparoscopic resection and 6 days with open resection (P chemotherapy was 52 with laparoscopic resection and 58 with open resection (P = 0.008). The 5-year overall survival was 89.6% in patients receiving chemotherapy in chemotherapy chemotherapy. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  10. MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Mohsen Taheri

    2013-01-01

    Full Text Available A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1 and multidrug resistance associated protein 1 (MRP1 in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor.

  11. Experiences of Syrian women with breast cancer regarding chemotherapy: a qualitative study.

    Science.gov (United States)

    Nizamli, Frial; Anoosheh, Monireh; Mohammadi, Essa

    2011-12-01

    The purpose of this study was to explore the experiences of Syrian women with breast cancer regarding their chemotherapy. A qualitative design, based on the content analysis approach, was used for the data collection and analysis of the perspectives of women with breast cancer in Syria. Semistructured interviews were carried out with 17 women who underwent chemotherapy after mastectomy in a chemotherapy center in Latakia between June and October 2010. Four main themes emerged from the study: psychological discomfort (negative emotion, body image, and depressive symtoms), physical problems (acute consequences of chemotherapy and general aspects of chemotherapy), social dysfunction (social isolation and lack of marriage opportunites), and failure in the family role (mother role and sexual relationship). Understanding the experiences of women with breast cancer regarding chemotherapy enables nurses to devise appropriate strategies to provide better support and care to patients in order to improve their quality of life. © 2011 Blackwell Publishing Asia Pty Ltd.

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

    DEFF Research Database (Denmark)

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

    Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross......-complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum......-based chemotherapy, and conversely, polymorphisms within encoding DNA repair enzymes or low repair capacity may confer sensitivity. A common single nucleotide polymorphism (SNP) of ERCC1 at codon 118 have been proposed to impair ERCC1 translation and reduce ERCC1 protein expression and consequently influence...

  13. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Science.gov (United States)

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Molecular chess? Hallmarks of anti-cancer drug resistance.

    Science.gov (United States)

    Cree, Ian A; Charlton, Peter

    2017-01-05

    The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients. The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to 'molecular chess'. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

  15. Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Høgdall, Claus; Karlsen, Mona Aarenstrup

    2017-01-01

    OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if micro...... and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel...

  16. An Exercise Intervention During Chemotherapy for Women With Recurrent Ovarian Cancer: A Feasibility Study.

    Science.gov (United States)

    Mizrahi, David; Broderick, Carolyn; Friedlander, Michael; Ryan, Mary; Harrison, Michelle; Pumpa, Kate; Naumann, Fiona

    2015-07-01

    The aim of this study was to determine the feasibility of a combined supervised and home-based exercise intervention during chemotherapy for women with recurrent ovarian cancer. Secondary aims were to determine the impact of physical activity on physical and psychological outcomes and on chemotherapy completion rates. Women with recurrent ovarian cancer were recruited from 3 oncology outpatient clinics in Sydney and Canberra, Australia. All participants received an individualized exercise program that consisted of 90 minutes or more of low to moderate aerobic, resistance, core stability, and balance exercise per week, for 12 weeks. Feasibility was determined by recruitment rate, retention rate, intervention adherence, and adverse events. Aerobic capacity, muscular strength, fatigue, sleep quality, quality of life, depression, and chemotherapy completion rates were assessed at weeks 0, 12, and 24. Thirty participants were recruited (recruitment rate, 63%), with a retention rate of 70%. Participants averaged 196 ± 138 min · wk of low to moderate physical activity throughout the intervention, with adherence to the program at 81%. There were no adverse events resulting from the exercise intervention. Participants who completed the study displayed significant improvements in quality of life (P = 0.017), fatigue (P = 0.004), mental health (P = 0.007), muscular strength (P = 0.001), and balance (P = 0.003) after the intervention. Participants completing the intervention had a higher relative dose intensity than noncompleters (P = 0.03). A program consisting of low to moderate exercise of 90 min · wk was achieved by two-thirds of women with recurrent ovarian cancer in this study, with no adverse events reported. Randomized control studies are required to confirm the benefits of exercise reported in this study.

  17. FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer

    Science.gov (United States)

    Zawlik, Izabela; Kaznowska, Ewa; Cebulski, Jozef; Kolodziej, Magdalena; Depciuch, Joanna; Vongsvivut, Jitraporn; Cholewa, Marian

    2016-11-01

    Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

  18. Effectiveness of Nursing Interventions on Physical and Psychological Outcome among Cancer Patients Undergoing Chemotherapy

    Directory of Open Access Journals (Sweden)

    T. Sivabalan

    2016-04-01

    Full Text Available Background: Cancer patient's undergoing chemotherapy experiences a variety of side effects which has influence on prognosis of illness, activity of daily living and the quality of life. There is a need of nursing care interventions for management and prevention of problem among cancer patients. Aim & Objectives: The present study aimed to assess the effectiveness of nursing interventions on physical and psychological outcome among cancer patients undergoing chemotherapy. Material and Methods: A true experimental study, post test only design with control group approach was conducted among 130 cancer patients undergoing chemotherapy at oncology ward of Pravara Rural Hospital, Loni (Bk, Ahmednagar, Maharashtra. Cancer patients who are 18 years old or older were selected with systematic random sampling method. Pre tested semi structured interview schedule was used to gather data. The assessment of health status before start of chemotherapy was carried out, followed by the nursing interventions was implemented based on patient needs and problems, and the post test was conducted after the period of interventions. The collected data was tabulated and analyzed using appropriate statistical methods wherever required. Results: The results revealed that the cancer patients experienced a wide range of physical and psychological problems prior to chemotherapy treatment. Cancer patients who received nursing interventions had improved post test mean scores on chemotherapy symptoms, pain and fatigue; emotional well being, anxiety and depression than the patients who received routine care, notably it was statistically significant at p<0.05 level. A significant association was observed between physical, psychological outcome variables and the socio demographic characteristics like sex, site of cancer, stage of cancer, duration of cancer, metastasis of cancer and the regimen of chemotherapy at p<0.05 level. Conclusion: This study demonstrated that the nursing

  19. Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

    Science.gov (United States)

    Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

    2016-01-01

    Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

  20. Electroejaculation before chemotherapy in adolescents and young men with cancer.

    Science.gov (United States)

    Hovav, Y; Dan-Goor, M; Yaffe, H; Almagor, M

    2001-04-01

    To evaluate the outcome of repeated electroejaculation for obtaining semen from adolescents and young men before initiation of anticancer therapies. Retrospective clinical study. Bikur Cholim Hospital, Jerusalem, Israel. Six young male patients (average age, 18+/-3 years) with diagnosed cancer who underwent 12 procedures of electroejaculation before chemotherapy. Transrectal electroejaculation. Semen was cryopreserved in small aliquots. Semen analysis. In all patients, semen was obtained by electroejaculation. Sperm count and motility were relatively low; mean values were 16 x 10(6) (range, 0--45 x 10(6)) and 14% (range, 0--53%) respectively. If necessary, electroejaculation can be performed in adolescents, and sperm may be obtained by repeated treatments over a short period.

  1. A Gene Expression Signature of Acquired Chemoresistance to Cisplatin and Fluorouracil Combination Chemotherapy in Gastric Cancer Patients

    Science.gov (United States)

    Kim, Hark Kyun; Choi, Il Ju; Kim, Chan Gyoo; Kim, Hee Sung; Oshima, Akira; Michalowski, Aleksandra; Green, Jeffrey E.

    2011-01-01

    Background We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives. Methodology/Principal Findings A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01) separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months). This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway), DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets) was an independent predictor for time to progression (adjusted P = 0.011) and survival (adjusted P = 0.034) of these 101 patients. Conclusion/Significance This signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF. PMID:21364753

  2. A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Hark Kyun Kim

    Full Text Available BACKGROUND: We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01 separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months. This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway, DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets was an independent predictor for time to progression (adjusted P = 0.011 and survival (adjusted P = 0.034 of these 101 patients. CONCLUSION/SIGNIFICANCE: This signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF.

  3. Smoothened antagonists reverse taxane resistance in ovarian cancer.

    Science.gov (United States)

    Steg, Adam D; Katre, Ashwini A; Bevis, Kerri S; Ziebarth, Angela; Dobbin, Zachary C; Shah, Monjri M; Alvarez, Ronald D; Landen, Charles N

    2012-07-01

    The hedgehog pathway has been implicated in the formation and maintenance of a variety of malignancies, including ovarian cancer; however, it is unknown whether hedgehog signaling is involved in ovarian cancer chemoresistance. The goal of this study was to determine the effects of antagonizing the hedgehog receptor, Smoothened (Smo), on chemotherapy response in ovarian cancer. Expression of hedgehog pathway members was assessed in three pairs of parental and chemotherapy-resistant ovarian cancer cell lines (A2780ip2/A2780cp20, SKOV3ip1/SKOV3TRip2, HeyA8/HeyA8MDR) using quantitative PCR and Western blot analysis. Cell lines were exposed to increasing concentrations of two different Smo antagonists (cyclopamine, LDE225) alone and in combination with carboplatin or paclitaxel. Selective knockdown of Smo, Gli1, or Gli2 was achieved using siRNA constructs. Cell viability was assessed by MTT assay. A2780cp20 and SKOV3TRip2 orthotopic xenografts were treated with vehicle, LDE225, paclitaxel, or combination therapy. Chemoresistant cell lines showed higher expression (>2-fold, P < 0.05) of hedgehog signaling components compared with their respective parental lines. Smo antagonists sensitized chemotherapy-resistant cell lines to paclitaxel, but not to carboplatin. LDE225 treatment also increased sensitivity of ALDH-positive cells to paclitaxel. A2780cp20 and SKOV3TRip2 xenografts treated with combined LDE225 and paclitaxel had significantly less tumor burden than those treated with vehicle or either agent alone. Increased taxane sensitivity seems to be mediated by a decrease in P-glycoprotein (MDR1) expression. Selective knockdown of Smo, Gli1, or Gli2 all increased taxane sensitivity. Smo antagonists reverse taxane resistance in chemoresistant ovarian cancer models, suggesting combined anti-hedgehog and chemotherapies could provide a useful therapeutic strategy for ovarian cancer. ©2012 AACR.

  4. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Anup Sharma

    Full Text Available Colorectal cancer (CRC is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment. For irinotecan (IRI, growth diminished by 16-62 fold as assessed, by both proliferation (IC50 and anchorage independent cell growth soft agar assays. Treatment of resistant HCT116 cell line along with in-vivo, for CRC line xenografts, AZA plus IRI again exhibits this synergistic response with significant improvement in survival and tumor regression in the mice. Genome-wide expression correlates changes in pathways for cell adhesion and DNA repair with the above responses. A Phase 1/2 clinical trial testing this concept is already underway testing the clinical efficacy of this concept in IRI resistant, metastatic CRC (NCT01896856.

  5. Use and duration of chemotherapy and its impact on survival in early-stage ovarian cancer.

    Science.gov (United States)

    Dinkelspiel, Helen E; Tergas, Ana I; Zimmerman, Lilli A; Burke, William M; Hou, June Y; Chen, Ling; Hillyer, Grace; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2015-05-01

    Although 5-year survival for early-stage ovarian cancer is favorable, prognosis at recurrence is poor, necessitating appropriate initial management. We examined the patterns of care and the impact of the duration of chemotherapy on survival for women with early-stage ovarian cancer. We used the SEER-Medicare database to identify women ≥ 65 years of age with stage I ovarian cancer diagnosed from 1992 to 2009. Patients were categorized as low-risk (non-clear cell histology, stage IA or IB, grade 1 or 2) or high-risk (clear cell histology, grade 3, or stage IC). We used multivariable logistic regression models to determine predictors of chemotherapy use and duration and Cox proportional hazards models to evaluate the effect of chemotherapy use and duration on survival. We identified 1394 patients. Among low-risk patients, 32.9% received adjuvant chemotherapy and the use of chemotherapy increased with time. Among high-risk patients, 71.9% received adjuvant chemotherapy; 44.2% had ≤ 3 months of treatment, and 55.8% had > 3 months of treatment. Older patients were less likely to receive chemotherapy, while those with higher stage and grade were more likely to receive chemotherapy (Pearly-stage ovarian cancer patients, practice patterns are widely divergent. Extended duration chemotherapy does not appear to impact survival for women with high-risk disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Starvation, detoxification, and multidrug resistance in cancer therapy

    Science.gov (United States)

    Lee, Changhan; Raffaghello, Lizzia; Longo, Valter D.

    2013-01-01

    The selection of chemotherapy drugs is based on the cytotoxicity to specific tumor cell types and the relatively low toxicity to normal cells and tissues. However, the toxicity to normal cells poses a major clinical challenge, particularly when malignant cells have acquired resistance to chemotherapy. This drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. Much progress in the understanding of tumor cell resistance has been made in the past 35 years, owing to milestone discoveries such as the identification and characterization of ABC transporters. Nonetheless, the complexity of the genetic and epigenetic rewiring of cancer cells makes drug resistance an equally complex phenomenon that is difficult to overcome. In this review, we discuss how the remarkable changes in the levels of glucose, IGF-I, IGFBP-1 and in other proteins caused by fasting have the potential to improve the efficacy of chemotherapy against tumors by protecting normal cells and tissues and possibly by diminishing multidrug resistance in malignant cells. PMID:22391012

  7. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    OpenAIRE

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemoth...

  8. Influence of taste disorders on dietary behaviors in cancer patients under chemotherapy

    OpenAIRE

    Laviano Alessandro; Rodríguez Cindy; Green-Renner Dan; Sosa-Sánchez Ricardo; Sánchez-Lara Karla; Motola-Kuba Daniel; Arrieta Oscar

    2010-01-01

    Abstract Objectives To determine the relationship between energy and nutrient consumption with chemosensory changes in cancer patients under chemotherapy. Methods We carried out a cross-sectional study, enrolling 60 subjects. Cases were defined as patients with cancer diagnosis after their second chemotherapy cycle (n = 30), and controls were subjects without cancer (n = 30). Subjective changes of taste during treatment were assessed. Food consumption habits were obtained with a food frequenc...

  9. Survival of metastatic colorectal cancer patients treated with chemotherapy in Alberta (1995?2004)

    OpenAIRE

    Chen, Yiqun; Qiu, Zhenguo; Kamruzzaman, Anmmd; Snodgrass, Tom; Scarfe, Andrew; Bryant, Heather E.

    2009-01-01

    Goals of work Clinical trials have suggested that advances in chemotherapy significantly improve the survival of patients with metastatic colorectal cancer. Comparable evidence from clinical practice is scarce. This study aims to investigate the survival of patients with metastatic colorectal cancer treated with chemotherapy in Alberta, Canada. Patients and methods Trends of relative survival of patients diagnosed in 1994?2003 were assessed using Alberta Cancer Registry (ACR) data. The median...

  10. The Effect of Painting on Depression in Children with Cancer Undergoing Chemotherapy

    OpenAIRE

    Tahmasebi, Zahra; Maghsoudi, Jahangir; Talakoub, Sedigeh

    2017-01-01

    Background: Psychological and social health of children with cancer may be severely affected by the disease and its treatment. Successive drawing by children can help them over time in terms of psychological and social adaptation. This study aimed to investigate the effects of drawing on depression in children with cancer undergoing chemotherapy. Materials and Methods: This quasi-experimental study was conducted on 7?12-year-old children with cancer undergoing chemotherapy. After completing M...

  11. Efficacy of Olanzapine Combined Therapy for Patients Receiving Highly Emetogenic Chemotherapy Resistant to Standard Antiemetic Therapy.

    Science.gov (United States)

    Abe, Masakazu; Kasamatsu, Yuka; Kado, Nobuhiro; Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Takekuma, Munetaka; Hirashima, Yasuyuki

    2015-01-01

    Olanzapine is proved to be effective for chemotherapy induced nausea and vomiting (CINV). But its efficacy in combination with standard antiemetic therapy is unknown. The purpose of this study is to prove the preventive effect of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy when used with standard antiemetic therapy. Gynecologic cancer patients receiving cisplatin-based chemotherapy who had grade 2 or 3 nausea in overall phase (0-120 h after chemotherapy) despite standard therapy were assigned to this study. From the next cycles to cycles in which patients developed grade 2 or 3 nausea, they received olanzapine with standard therapy. 5 mg oral olanzapine was administered for 7 days from the day before chemotherapy. The effectiveness of preventive administration of olanzapine was evaluated retrospectively. The primary endpoint was nausea control rate (grade 0 or 1) with olanzapine. Fifty patients were evaluable. The nausea control rate with olanzapine was improved from 58% to 98% in acute phase (0-24 h after chemotherapy) and 2% to 94% in delayed phase (24-120 h after chemotherapy). In overall phase, the nausea control rate improved from 0% to 92%, and it was statistically significant (P improvement in control of refractory nausea.

  12. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jorge L. Soriano

    2011-01-01

    Full Text Available The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily, in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum, followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD was 18,43 months (12,20–24,10 months, being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  13. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    Science.gov (United States)

    Soriano, Jorge L.; Batista, Noyde; Santiesteban, Eduardo; Lima, Mayté; González, Joaquín; García, Robin; Zarza, Yohanka; López, María V.; Rodríguez, Myriam; Loys, Jorge L.; Montejo, Narciso; Aguirre, Frank; Macías, Amparo; Vázquez, Ana M.

    2011-01-01

    The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20–24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration. PMID:22295231

  14. Six-month follow-up of patient-rated outcomes in a randomized controlled trial of exercise training during breast cancer chemotherapy.

    Science.gov (United States)

    Courneya, Kerry S; Segal, Roanne J; Gelmon, Karen; Reid, Robert D; Mackey, John R; Friedenreich, Christine M; Proulx, Caroline; Lane, Kirstin; Ladha, Aliya B; Vallance, Jeffrey K; Liu, Qi; Yasui, Yutaka; McKenzie, Donald C

    2007-12-01

    Few exercise trials in cancer patients have reported longer-term follow-up. Here, we report a 6-month follow-up of exercise behavior and patient-rated outcomes from an exercise trial in breast cancer patients. Breast cancer patients initiating adjuvant chemotherapy (n = 242) were randomly assigned to usual care (n = 82), resistance exercise training (RET; n = 82), or aerobic exercise training (AET; n = 78) for the duration of their chemotherapy. At 6-month follow-up, participants were mailed a questionnaire that assessed quality of life, self-esteem, fatigue, anxiety, depression, and exercise behavior. Two hundred one (83.1%) participants provided 6-month follow-up data. Adjusted linear mixed-model analyses showed that, at 6-month follow-up, the RET group reported higher self-esteem [adjusted mean difference, 1.6; 95% confidence interval (95% CI), 0.1-3.2; P = 0.032] and the AET group reported lower anxiety (adjusted mean difference, -4.7; 95% CI, -0.0 to -9.3; P = 0.049) compared with the usual care group. Moreover, compared with participants reporting no regular exercise during the follow-up period, those reporting regular aerobic and resistance exercise also reported better patient-rated outcomes, including quality of life (adjusted mean difference, 9.5; 95% CI, 1.2-17.8; P = 0.025). Improvements in self-esteem observed with RET during breast cancer chemotherapy were maintained at 6-month follow-up whereas reductions in anxiety not observed with AET during breast cancer chemotherapy emerged at 6-month follow-up. Moreover, adopting a combined aerobic and resistance exercise program after breast cancer chemotherapy was associated with further improvements in patient-rated outcomes. Exercise training during breast cancer chemotherapy may result in some longer-term and late effects for selected patient-rated outcomes.

  15. Long-term cognitive function following chemotherapy in patients with testicular cancer

    DEFF Research Database (Denmark)

    Pedersen, Anders Degn; Rossen, Philip; Mehlsen, Mimi Yung

    2009-01-01

    Cancer patients frequently report cognitive complaints following chemotherapy, but the results from the available studies, mainly of women with breast cancer, are inconsistent. Our aim was to compare cognitive function of men with testicular cancer (TC) who had orchiectomy and chemotherapy...... (bleomycin, etoposide, cisplatin) with men who had orchiectomy only or orchiectomy and radiotherapy. Thirty-six chemotherapy patients and 36 nonchemotherapy patients were tested 2-7 years after treatment for TC with standardized neuropsychological tests. Chemotherapy and nonchemotherapy patients displayed...... similar performances on cognitive tests (p values adjusted for multiple comparisons: .63-1.00). Moreover, there was no difference in the proportion of cognitively impaired patients in the chemotherapy group (5.6%) compared to the nonchemotherapy group (8.3%) (chi2 = 0.22, p = .64). Our results...

  16. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2016-10-01

    recruitment and consent Funding support DOD-PCRP, American Cancer Society DOD-PCRP American Cancer Society DOD-PCRP, American Cancer...study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene...enriched by depleting hematopoietic cells. For this purpose CD45, which is expressed on the surface of all leukocytes and their progenitors,9 is commonly

  17. Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study.

    Science.gov (United States)

    Greenlee, Heather; Neugut, Alfred I; Falci, Laura; Hillyer, Grace Clarke; Buono, Donna; Mandelblatt, Jeanne S; Roh, Janise M; Ergas, Isaac J; Kwan, Marilyn L; Lee, Marion; Tsai, Wei Yann; Shi, Zaixing; Lamerato, Lois; Kushi, Lawrence H; Hershman, Dawn L

    2016-09-01

    Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among

  18. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

    Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  19. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    Science.gov (United States)

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  20. Efflux Pump.Mediated Resistance in Chemotherapy | Ughachukwu ...

    African Journals Online (AJOL)

    more important to the clinician and pharmacologist, as they constitute an important cause of antimicrobial drug resistance, which contributes to treatment failure, high medical bills, and increased mortality / morbidity. This review was aimed at highlighting the role of efflux pump mechanisms in microbial resistance to ...

  1. Chemotherapy for testicular cancer induces acute alterations in diastolic heart function

    NARCIS (Netherlands)

    Schinkel, L.D. van; Willemse, P.M.; Meer, R.W. van der; Burggraaf, J.; Elderen, S.G. van; Smit, J.W.A.; Roos, A. de; Osanto, S.; Lamb, H.J.

    2013-01-01

    Background:After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore

  2. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xu Chao

    Full Text Available BACKGROUND: Magnetic nanoparticles (NPs loaded with antitumor drugs in combination with an external magnetic field (EMF-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1 to investigate application of PEG modified GMNPs (PGMNPs as a drug carrier of the chemotherapy compound doxorubicin (DOX in vitro; 2 to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs using an EMF-guided delivery in vivo. METHODS: First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M. RESULTS: The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each p<0.05, following treatment for 33 days. The life span of tumor-bearing mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX were 74.8±9.95, 66.1±13.5, and 31.3±3.31 days, respectively (each p<0.05. CONCLUSION: This simple and adaptive nanoparticle design may accommodate chemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.

  3. Castration-resistant prostate cancer: systemic therapy in 2012

    Directory of Open Access Journals (Sweden)

    Fernando C. Maluf

    2012-01-01

    Full Text Available Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

  4. Castration-resistant prostate cancer: systemic therapy in 2012

    Science.gov (United States)

    Maluf, Fernando C.; Smaletz, Oren; Herchenhorn, Daniel

    2012-01-01

    Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer. PMID:22522765

  5. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

    Science.gov (United States)

    Aebi, Stefan; Gelber, Shari; Anderson, Stewart J; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P; Geyer, Charles E; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L

    2014-02-01

    Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who

  6. Chemotherapy versus support cancer treatment in advanced gastric cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    L. Casaretto

    2006-04-01

    Full Text Available The aim of the present study was to compare the efficacy of chemotherapy and support treatment in patients with advanced non-resectable gastric cancer in a systematic review and meta-analysis of randomized clinical trials that included a comparison of chemotherapy and support care treatment in patients diagnosed with gastric adenocarcinoma, regardless of their age, gender or place of treatment. The search strategy was based on the criteria of the Cochrane Base, using the following key words: 1 randomized clinical trials and antineoplastic combined therapy or gastrointestinal neoplasm, 2 stomach neoplasm and drug therapy, 3 clinical trial and multi-modality therapy, 4 stomach neoplasm and drug therapy or quality of life, 5 double-blind method or clinical trial. The search was carried out using the Cochrane, Medline and Lilacs databases. Five studies fulfilled the inclusion criteria, for a total of 390 participants, 208 (53% receiving chemotherapy, 182 (47% receiving support care treatment and 6 losses (1.6%. The 1-year survival rate was 8% for support care and 20% for chemotherapy (RR = 2.14, 95% CI = 1.00-4.57, P = 0.05; 30% of the patients in the chemotherapy group and 12% in the support care group attained a 6-month symptom-free period (RR = 2.33, 95% CI = 1.41-3.87, P < 0.01. Quality of life evaluated after 4 months was significantly better for the chemotherapy patients (34%; RR = 2.07, 95% CI = 1.31-3.28, P < 0.01 with tumor mass reduction (RR = 3.32, 95% CI = 0.77-14.24, P = 0.1. Chemotherapy increased the 1-year survival rate of the patients and provided a longer symptom-free period of 6 months and an improvement in quality of life.

  7. Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial.

    Science.gov (United States)

    Courneya, Kerry S; Segal, Roanne J; Mackey, John R; Gelmon, Karen; Friedenreich, Christine M; Yasui, Yutaka; Reid, Robert D; Jespersen, Diana; Cook, Diane; Proulx, Carolyn; Trinh, Linda; Dolan, Lianne B; Wooding, Evyanne; Forbes, Cynthia C; McKenzie, Donald C

    2014-04-01

    To examine the effects of different doses and types of exercise on sleep quality in breast cancer patients receiving chemotherapy. A multicenter trial in Canada randomized 301 breast cancer patients between 2008 and 2011 to thrice weekly, supervised exercise during chemotherapy consisting of either a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101), or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104). The secondary sleep outcomes in the trial were assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline, twice during chemotherapy, and postchemotherapy. We analyzed the global PSQI and the component scores. Repeated measures analyses of variance indicated that the HIGH group was statistically superior to the STAN group for global sleep quality (mean group difference = -0.90; 95 % CI -0.05 to -1.76; p = 0.039) as well as subjective sleep quality (p = 0.028) and sleep latency (p = 0.049). The COMB group was borderline statistically superior to the STAN group for global sleep quality (mean group difference = -0.76; 95 % CI +0.11 to -1.62; p = 0.085) as well as sleep duration (p = 0.051); and statistically superior for sleep efficiency (p = 0.040), and percentage of poor sleepers (p = 0.045). Compared to a standard volume of aerobic exercise, higher volumes of both aerobic and combined exercise improved some aspects of sleep quality during breast cancer chemotherapy. Exercise may be an attractive option to manage sleep dysfunction in cancer patients during chemotherapy.

  8. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    Science.gov (United States)

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  9. SU-E-J-31: Biodynamic Imaging of Cancer Tissue and Response to Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nolte, D; Turek, J; Childress, M; An, R; Merrill, D [Purdue University, West Lafayette, IN (United States); Matei, D [Indiana University School of Medicine, Indianapolis, IN (United States)

    2014-06-01

    Purpose: To measure intracellular motions inside three-dimensional living cancer tissue samples to establish a novel set of biodynamic biomarkers that assess tissue proliferative activity and sensitivity or resistance to chemotherapy. Methods: Biodynamic imaging (BDI) uses digital holography with low-coherence low-intensity light illumination to construct 3D holograms from depths up to a millimeter deep inside cancer tissue models that include multicellular tumor spheroids and ex vivo cancer biopsies from canine non-Hodgkins lymphoma and epithelial ovarian cancer (EOC) mouse explants. Intracellular motions modulate the holographic intensity with frequencies related to the Doppler effect caused by the motions of a wide variety of intracellular components. These motions are affected by applied therapeutic agents, and BDI produces unique fingerprints of the action of specific drugs on the motions in specific cell types. In this study, chemotherapeutic agents (doxorubicin for canine lymphoma and oxoplatin for ovarian) are applied to the living tissue models and monitored over 10 hours by BDI. Results: Multicellular spheroids and patient biopsies are categorized as either sensitive or insensitive to applied therapeutics depending on the intracellular Doppler signatures of chemotherapy response. For both lymphoma and EOC there is strong specificity to the two types of sensitivities, with sensitive cell lines and biopsies exhibiting a global cessation of proliferation and strong suppression of metabolic activity, while insensitive cell lines and biopsies show moderate activation of Doppler frequencies associated with membrane processes and possible membrane trafficking. Conclusion: This work supports the hypothesis that biodynamic biomarkers from three-dimensional living tumor tissue, that includes tissue heterogeneity and measured within 24 hours of surgery, is predictive of near-term patient response to therapy. Future work will correlate biodynamic biomarkers with

  10. Long non-coding RNAs in anti-cancer drug resistance.

    Science.gov (United States)

    Chen, Qin-Nan; Wei, Chen-Chen; Wang, Zhao-Xia; Sun, Ming

    2017-01-03

    Chemotherapy is one of the basic treatments for cancers; however, drug resistance is mainly responsible for the failure of clinical treatment. The mechanism of drug resistance is complicated because of interaction among various factors including drug efflux, DNA damage repair, apoptosis and targets mutation. Long non-coding RNAs (lncRNAs) have been a focus of research in the field of bioscience, and the latest studies have revealed that lncRNAs play essential roles in drug resistance in breast cancer, gastric cancer and lung cancer, et al. Dysregulation of multiple targets and pathways by lncRNAs results in the occurrence of chemoresistance. In this review, we will discuss the mechanisms underlying lncRNA-mediated resistance to chemotherapy and the therapeutic potential of lncRNAs in future cancer treatment.

  11. Is chemotherapy always required for cancer in pregnancy? An observational study.

    Science.gov (United States)

    Walsh, E M; O'Kane, G M; Cadoo, K A; Graham, D M; Korpanty, G J; Power, D G; Carney, D N

    2017-11-01

    Cancer in pregnancy is relatively rare, but the incidence is increasing. Several studies show that cytotoxic agents are safe to use in pregnancy from the second trimester onwards. This study assesses the maternal and foetal outcomes of cancers diagnosed during pregnancy. In particular, it focuses on a subset of women who elected to defer systemic chemotherapy until after delivery. This study examines if all cancers need to be treated during pregnancy or if, in certain cases, treatment can be safely deferred until after full-term delivery. This is a retrospective observational study of women diagnosed with cancer during pregnancy in an Irish cancer centre over a 27-year period. All women diagnosed with cancer during pregnancy who were referred to the medical oncology department for consideration of chemotherapy were included in this study. Medical and pharmacy records were extensively reviewed. Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology for consideration of systemic chemotherapy. Sixteen women (64%) commenced chemotherapy during pregnancy, seven women (28%) did not receive chemotherapy while pregnant, but commenced treatment immediately after delivery, and two (8%) did not receive any systemic chemotherapy at all. Of the seven women who commenced chemotherapy after delivery, six (85.7%) were diagnosed before 30/40 gestation. There were three cases of Hodgkin's lymphoma, two breast cancers and one ovarian cancer. After a median follow-up of 12 years, all six mothers remain disease-free. This study identified a select cohort of patients that did not receive chemotherapy during pregnancy. There were no adverse outcomes to mothers due to delayed treatment.

  12. Correlation of NSE and ProGRP levels in patients with small cell lung cancer before and after chemotherapy with cancer cell apoptosis caused by chemotherapy

    Directory of Open Access Journals (Sweden)

    Wen-Yu Lu1

    2017-04-01

    Full Text Available Objective: To study the correlation of NSE and ProGRP levels in patients with small cell lung cancer (SCLC before and after chemotherapy with cancer cell apoptosis caused by chemotherapy. Methods: Patients with SCLC accepting EP chemotherapy in our hospital between August 2014 and October 2016 were selected, serum was collected before chemotherapy and after 3 cycles of chemotherapy respectively to determine NSE and ProGRP levels, the quartile of serum NSE and ProGRP levels after chemotherapy were referred to divide the patients into NSE and ProGRP-1 group, -2 group, -3 and -4 group from low to high; tumor lesions were collected to determine apoptosis molecule mRNA expression. Results: After chemotherapy, serum NSE and ProGRP levels of patients with SCLC were significantly lower than those before chemotherapy, and Fas, FasL, Caspase-8, Caspase-3, pULK and PI3KC3 mRNA expression in tumor lesion were significantly higher than those before chemotherapy; Fas, FasL, Caspase-8, Caspase-3, pULK and PI3KC3 mRNA expression in lesions of NSE and ProGRP-1 group, -2 group and -3 group were significantly higher than those of NSE and ProGRP-4 group, Fas, FasL, Caspase-8, Caspase-3, pULK and PI3KC3 mRNA expression in lesions of NSE and ProGRP-1 group and -2 group were significantly higher than those of NSE and ProGRP-3 group, and Fas, FasL, Caspase-8, Caspase-3, pULK and PI3KC3 mRNA expression in lesions of NSE and ProGRP-1 group were significantly higher than those of NSE and ProGRP-2 group. Conclusion: Serum NSE and ProGRP levels decrease significantly in patients with small cell lung cancer after chemotherapy, and they are closely related to the cancer cell apoptosis caused by chemotherapy.

  13. Effect of Chemotherapy on the Quality of Life of Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xu LIU

    2013-12-01

    Full Text Available Background and objective With development of modern medicine, eliminating patients’ pain and mental disorder and improving the quality of life has become an important problem in patients with cancer. The aim of this study is to observe the impact of chemotherapy on quality of life and influencing factor of quality of life among lung cancer patients. Methods Sixty-one lung cancer patients were assessed with clinical outcomes and the EORTC QLQ-C30 questionnaires before chemotherapy, one week after 2 cycles of chemotherapy, one week after 4 cycles of chemotherapy. Results After 2 cycles of chemotherapy, effective rate was 40.0%. Social function decreased. Nause and vomiting, insomnia and appetite loss deteriorated (P0.05. Grouped according to the plasma albumin level, the difference wasn’t statistically significant (P>0.05. In hypoproteinemia group, symptoms and economic difficulties score was higher; High protein group, function and general health scores was higher. Conclusion After the chemotherapy, patients’ the lesion of cancer became smaller and clinical symptoms relieved, but some patients, fatigue, appetite loss, nausea and vomiting symptom deteriorated, emotion became bad. Quality of life of lung cancer patients decrease. We should pay more attention to the adverse reactions of chemotherapy and cope with them, give positive psychological intervention and improve patients, nutrition to improve the quality of life.

  14. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets

    Science.gov (United States)

    Balko, Justin M.; Giltnane, Jennifer M.; Wang, Kai; Schwarz, Luis J.; Young, Christian D.; Cook, Rebecca S.; Owens, Phillip; Sanders, Melinda E.; Kuba, Maria G.; Sánchez, Violeta; Kurupi, Richard; Moore, Preston D.; Pinto, Joseph A.; Doimi, Franco D.; Gómez, Henry; Horiuchi, Dai; Goga, Andrei; Lehmann, Brian D.; Bauer, Joshua A.; Pietenpol, Jennifer A.; Ross, Jeffrey S.; Palmer, Gary A.; Yelensky, Roman; Cronin, Maureen; Miller, Vincent A.; Stephens, Phillip J.; Arteaga, Carlos L.

    2014-01-01

    Neoadjuvant chemotherapy (NAC) induces a pathologic complete response (pCR) in approximately 30% of patients with triple-negative breast cancers (TNBC). In patients lacking a pCR, NAC selects a subpopulation of chemotherapy-resistant tumor cells. To understand the molecular underpinnings driving treatment-resistant TNBCs, we performed comprehensive molecular analyses on the residual disease (RD) of 74 clinically-defined TNBCs after NAC including next-generation sequencing (NGS) on 20 matched pre-treatment biopsies. Combined NGS and digital RNA expression analysis identified diverse molecular lesions and pathway activation in drug-resistant tumor cells. Ninety percent of the tumors contained a genetic alteration potentially treatable with a currently available targeted therapy. Thus, profiling residual TNBCs after NAC identifies targetable molecular lesions in the chemotherapy-resistant component of the tumor which may mirror micro-metastases destined to recur clinically. These data can guide biomarker-driven adjuvant studies targeting these micro-metastases to improve the outcome of patients with TNBC who do not respond completely to NAC. PMID:24356096

  15. Safety and feasibility of a combined exercise intervention for inoperable lung cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Quist, Morten; Rørth, Mikael; Langer, Seppo

    2012-01-01

    To investigate the safety and feasibility of a six-week supervised structured exercise and relaxation training programme on estimated peak oxygen consumption, muscle strength and health related quality of life (HRHRQOL) in patients with inoperable lung cancer, undergoing chemotherapy....

  16. Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review

    NARCIS (Netherlands)

    Sloothaak, D. A. M.; Mirck, B.; Punt, C. J. A.; Bemelman, W. A.; van der Bilt, J. D. W.; D'Hoore, A.; Tanis, P. J.

    2014-01-01

    Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC. A systematic search of literature was

  17. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2017-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

  18. Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer

    NARCIS (Netherlands)

    Jansman, FGA; Sleijfer, DT; de Graaf, JC; Coenen, JLLM; Brouwers, JRBJ

    2001-01-01

    The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in

  19. 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

  20. Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy.

    Science.gov (United States)

    Bansal, Tripta; Jaggi, Manu; Khar, Roop K; Talegaonkar, Sushama

    2009-01-01

    Chemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport. Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the

  1. Quality of Sleep and Related Factors During Chemotherapy in Patients with Stage I/II Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hsiao-Hsuan Kuo

    2006-01-01

    Conclusion: The study showed poor sleep quality and daytime sleepiness in patients with breast cancer during the active phase of chemotherapy. Chemotherapy may bring symptom distress to patients and adversely influence sleep quality.

  2. Major Clinical Impact of Platinum-Based Chemotherapy in a Patient with a Borderline Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2009-09-01

    Full Text Available A patient with extensive and painful chest wall involvement from a metastatic borderline cancer of the ovary was treated with a carboplatin plus paclitaxel chemotherapy regimen. She achieved a rather dramatic improvement of pain control, a significant biochemical response with 75% reduction of the CA-125 antigen level, but only limited radiographic tumor regression. This experience emphasizes the potential clinical utility of platinum-based cytotoxic chemotherapy in the setting of symptomatic advanced borderline ovarian cancer.

  3. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

    OpenAIRE

    Allen, Valerie A.; Manahan, Kelly J; Geisler, John P.

    2016-01-01

    Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite...

  4. Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine.

    Science.gov (United States)

    Wang, Zhijun; Liu, Xuefeng; Ho, Rebecca Lucinda Ka Yan; Lam, Christopher Wai Kei; Chow, Moses Sing Sum

    2016-07-07

    Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy.

  5. A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients.

    Science.gov (United States)

    Jansen, Catherine E; Cooper, Bruce A; Dodd, Marylin J; Miaskowski, Christine A

    2011-10-01

    Evidence for chemotherapy-induced cognitive impairment remains inconclusive. This study was designed to determine the trajectory of cognitive function over time in women with breast cancer, who received doxorubicin and cyclophosphamide (AC) alone or followed by a taxane. Associations between changes in cognitive function and potential covariates including anxiety, depression, fatigue, hemoglobin level, menopausal status, and perception of cognitive function were evaluated. The Repeatable Battery for the Assessment of Neuropsychological Status, Stroop Test, and Grooved Pegboard were used to assess cognitive function in a group of 71 women prior to chemotherapy, a week after completing the last cycle of AC, as well as 1 week and 6 months after the completion of all chemotherapy. Cognitive impairment was found in 23% of women prior to chemotherapy. Hierarchical linear modeling showed significant decreases after receiving chemotherapy followed by improvements 6 months after the completion of chemotherapy in the cognitive domains of visuospatial skill (p cancer diagnosis may be associated with cognitive impairment. While chemotherapy may have a negative impact on cognitive function, chemotherapy-related impairments appear to be more acute than chronic side effects of therapy. Further studies are needed to provide insight into the clinical significance and potential mechanisms of cancer and treatment-related cognitive impairments.

  6. ROLES OF RADIATION DOSE AND CHEMOTHERAPY IN THE ETIOLOGY OF STOMACH CANCER AS A SECOND MALIGNANCY

    NARCIS (Netherlands)

    van den Belt-Dusebout, Alexandra W.; Aleman, Berthe M. P.; Besseling, Gijs; de Bruin, Marie L.; Hauptmann, Michael; van 't Veer, Mars B.; de Wit, Ronald; Ribot, Jacques G.; Noordijk, Evert M.; Kerst, J. Martijn; Gietema, Jourik A.; van Leeuwen, Flora E.

    2009-01-01

    Purpose: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma. Methods and Materials: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated

  7. Cancer chemotherapy of the upper aero digestive tract; Chimiotherapie des cancers des voies aerodigestives superieures

    Energy Technology Data Exchange (ETDEWEB)

    Vedrine, L.; Chargari, C.; Le Moulec, S.; Fayolle, M.; Ceccaldi, B.; Bauduceau, O. [Hopital d' Instruction des Armees du Val-de-Grace, Service d' Oncologie et Radiotherapie, 75 - Paris (France)

    2008-03-15

    Tumours of the upper aero digestive tract represent the sixth most frequent kind of cancer in France and throughout the world. If the localised forms may be controlled in the long run in two thirds of cases by surgery or radiotherapy, only one third of locally advanced forms are accessible to a cure after association from radiotherapy and chemotherapy. Besides, with a median of survival less than six months, metastatic tumours present a catastrophic spontaneous prognosis among patients with a medical ground that is often heavily deteriorated by prolonged exposure to alcohol and tobacco. Thus, there is a necessity to implement adapted therapeutic strategies to each patient and based on satisfactory proof levels of effectiveness. Optimisation of existing chemotherapy protocols and development of new therapies, in particular of targeted therapies, remain an important objective in the hope to improve results of treatments in locally advanced and metastatic cancers of the oral cavity. (authors)

  8. Multidrug-resistant hepatocellular carcinoma cells are enriched for ...

    African Journals Online (AJOL)

    Chemotherapy is a main treatment for cancer, while multidrug-resistance is the main reason for chemotherapy failure, and tumor relapse and metastasis. Cancer stem cells or cancer stem-like cells (CSCs) are a small subset of cancer cells, which may be inherently resistant to the cytotoxic effect of chemotherapy.

  9. Predictors of hope among women with breast cancer during chemotherapy.

    Science.gov (United States)

    Balsanelli, Alessandra Cristina Sartore; Grossi, Sonia Aurora Alves

    2016-01-01

    Identifying the predictors of hope in patients with breast cancer during chemotherapy treatment. A prospective longitudinal study. The sample was composed of 122 women who responded to the instruments of hope, anxiety and depression, coping, fatigue, religiosity and self-esteem in the first and last cycle of chemotherapy. These variables were used in adjusting the logistic regression model that characterized multivariate statistics, allowing identification of predictor variables. The increase of hope at the end of chemotherapy treatment was statistically significant (p = 0.012). The delay in undergoing treatment from the onset of breast cancer symptoms, Karnofsky Performance Status, depression, self-esteem and pain were characterized as factors being associated to hope by univariate analysis. Among the variables analyzed, pain was the only predicting factor of hope. Pain was the predicting factor in this sample. Hope increased during treatment and revealed the following associated factors: Karnofsky Performance Status, delay in starting the treatment, depression, self-esteem and pain. This study brought forth a multidisciplinary contribution, allowing for understanding the factors that can influence hope and presenting support to nursing care. The data evidenced conditions of improvement or worsening of hope, which requires interdisciplinary attention in Oncology. Identificar os fatores preditores da esperança nas pacientes com câncer de mama em tratamento quimioterápico. Estudo prospectivo longitudinal. A amostra foi de 122 mulheres que responderam aos instrumentos de esperança, ansiedade e depressão, coping, fadiga, religiosidade e autoestima no primeiro e no último ciclo de quimioterapia. Essas variáveis foram utilizadas no ajuste do modelo de regressão logística que caracterizou a estatística multivariada permitindo a identificação das variáveis preditoras. O aumento da esperança ao final do tratamento quimioterápico foi estatisticamente

  10. Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients.

    Science.gov (United States)

    Black, David S; Peng, Cheng; Sleight, Alix G; Nguyen, Nathalie; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-08-15

    The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients. A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness. An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (β = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P mindfulness practice during chemotherapy can reduce the blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

  11. Fatigue, sleep, and circadian rhythms prior to chemotherapy for breast cancer

    Science.gov (United States)

    Ancoli-Israel, Sonia; Liu, Lianqi; Marler, Matthew R.; Parker, Barbara A.; Jones, Vicky; Sadler, Georgia Robins; Dimsdale, Joel; Cohen-Zion, Mairav; Fiorentino, Lavinia

    2006-01-01

    Goals Previous investigations have shown that women undergoing chemotherapy for breast cancer experience both disturbed sleep and fatigue. However, most of the previous research examined women either during or after chemotherapy. This study examined sleep, fatigue, and circadian rhythms in women with breast cancer before the start of chemotherapy. Patients and methods Eighty five women with Stages I–IIIA breast cancer who were scheduled to begin adjuvant or neo-adjuvant anthracycline-based chemotherapy participated. Each had sleep/wake activity recorded with actigraphy for 72 consecutive hours and filled out questionnaires on sleep, fatigue, depression, and functional outcome. Main results On average, the women slept for about 6 h a night and napped for over an hour during the day. Sleep was reported to be disturbed and fatigue levels were high. Circadian rhythms were robust, but women who were more phase-delayed reported more daily dysfunction (p<0.01). Conclusions The data from the current study suggest that the women with breast cancer likely experience both disturbed sleep and fatigue before the beginning of chemotherapy. Although their circadian rhythms are robust, breast cancer patients with more delayed rhythms experience more daily dysfunction secondary to fatigue. These data suggest that strategies to improve disturbed sleep and to phase-advance circadian rhythms prior to initiation of chemotherapy may be beneficial in improving daily function in breast cancer patients. PMID:16010529

  12. Neoadjuvant chemotherapy is associated with improved survival compared with adjuvant chemotherapy in patients with triple-negative breast cancer only after complete pathologic response.

    Science.gov (United States)

    Fisher, Carla S; Ma, Cynthia X; Gillanders, William E; Aft, Rebecca L; Eberlein, Timothy J; Gao, Feng; Margenthaler, Julie A

    2012-01-01

    Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy. We performed a retrospective chart review and identified 385 patients with stage I-III TNBC who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. Patients were divided according to receipt of neoadjuvant chemotherapy with pCR, neoadjuvant chemotherapy without pCR, and adjuvant chemotherapy. Data were compared using Fisher's exact test and analysis of variance (ANOVA). Kaplan-Meier curves were generated. Of 385 patients, 151 (39%) received neoadjuvant chemotherapy and 234 (61%) received adjuvant chemotherapy. Twenty-six (17%) of those patients receiving neoadjuvant chemotherapy had pCR. After controlling for covariates associated with survival in unadjusted tests, patients undergoing neoadjuvant chemotherapy with residual tumor had significantly worse survival compared with patients receiving adjuvant therapy [hazard ratio (HR) = 0.51, P = 0.007] and a trend towards worse survival compared with patients receiving neoadjuvant therapy with pCR (HR = 0.19, P = 0.10). Although previous clinical trials have not demonstrated a survival difference between patients receiving neoadjuvant versus adjuvant chemotherapy for breast cancer, our study suggests an overall survival benefit in patients with pCR following neoadjuvant chemotherapy compared with patients receiving adjuvant therapy. It is clear that a prospective study needs to be carried out to better elucidate the timing of chemotherapy in patients with TNBC.

  13. Changes in the gastric potential difference during chemotherapy in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Fabrin, B; Højgaard, L; Mouridsen, H T

    1991-01-01

    Nausea and vomiting are frequent side-effects of intravenous cancer chemotherapy. How these complications were related to the gastric mucosal function was investigated by measuring the gastric mucosal potential difference (PD). Eight patients with metastatic breast cancer receiving chemotherapy...... were investigated. The liquid junction-corrected gastric PD and pH were measured with a newly developed microelectrode. The measurements started half an hour before chemotherapy and continued for 4-5 hours. Nausea, vomiting, psychological stress and sleeping episodes were registered. The initial PD...

  14. Intravesical chemotherapy in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Sima P Porten

    2015-01-01

    Full Text Available Non-muscle-invasive bladder cancer (NMIBC is characterized by a tendency for recurrence and capacity for progression. Intravesical instillation therapy has been employed in various clinical settings, which are summarized within this review. Several chemotherapeutic agents have shown clinical efficacy in reducing recurrence rates in the post-transurethral resection of bladder tumor (TURBT setting, including mitomycin C (MMC, doxorubicin, and epirubicin. Mounting evidence also supports the use of intravesical MMC following nephroureterectomy to reduce later urothelial bladder recurrence. In the adjuvant setting, bacillus Calmette-Guérin (BCG immunotherapy is an established first-line agent in the management of carcinoma in situ (CIS and high-grade non muscle invasive urothelial carcinoma (UC. Among high and intermediate-risk patients (based on tumor grade, size, and focality improvements in disease-free intervals have been seen with adjunctive administration of MMC prior to scheduled BCG dosing. Following failure of first-line intravesical therapy, gemcitabine and valrubicin have demonstrated modest activity, though valrubicin remains the only agent currently Food and Drug Administration (FDA-approved for the treatment of BCG-refractory CIS. Techniques to optimize intravesical chemotherapy delivery have also been explored including pharmacokinetic methods such as urinary alkalization and voluntary dehydration. Chemohyperthermia and electromotive instillation have been associated with improved freedom from recurrence intervals but may be associated with increased urinary toxicity. Improvements in therapeutic selection may be heralded by novel opportunities for genomic profiling and refinements in clinical risk stratification.

  15. Infrared Spectroscopy in Cancer Diagnosis and Chemotherapy Monitoring

    Science.gov (United States)

    Tolstorozhev, G. B.; Bel'kov, M. V.; Skornyakov, I. V.; Butra, V. A.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, N. I.; Kutsenko, I. P.; Sharykina, N. I.

    2014-07-01

    We demonstrate that IR spectroscopic analysis can be used in diagnosis and chemotherapy monitoring for cancers of various organs at the molecular level. We used Fourier transform IR spectroscopy to study human breast and thyroid tumor tissues which were removed during surgery. The characteristic frequencies of C = O stretching vibrations in the IR spectra of tissues of pathological foci were compared with data from histological examination. In the IR spectra of healthy tissues or for benign tumors, the most intense absorption bands ν(C = O) are located in the interval 1675-1650 cm-1. When malignant neoplasms are present in the organs, the intensity of the bands in this range of the spectrum is reduced, while the intensities of the absorption bands in the 1710-1680 cm-1 interval increase. We also studied lung tissue for mice of the C57B1/6 line for healthy tissue and after implantation of B-16 melanoma tumor. The IR spectra of healthy mouse lung tissue and mouse lung tissue with B-16 melanoma metastases in the region of the C = O stretching vibrations display the same differences. We found that when lung malignancy was treated with the optimal dose of a synthesized drug based on palladium complexes of methylenediphosphonic acid, the spectroscopic signs of the presence of metastases in the lungs disappear, and the IR spectrum of the lung tissue after treatment practically coincides with the spectrum of healthy lung tissue.

  16. Cell kinetic modelling and the chemotherapy of cancer

    CERN Document Server

    Knolle, Helmut

    1988-01-01

    During the last 30 years, many chemical compounds that are active against tumors have been discovered or developed. At the same time, new methods of testing drugs for cancer therapy have evolved. nefore 1964, drug testing on animal tumors was directed to observation of the incfease in life span of the host after a single dose. A new approach, in which the effects of multiple doses on the proliferation kinetics of the tumor in vivo as well as of cell lines in vitro are investigated, has been outlined by Skipper and his co-workers in a series of papers beginning in 1964 (Skipper, Schabel and Wilcox, 1964 and 1965). They also investigated the influence of the time schedule in the treatment of experimental tumors. Since the publication of those studies, cell population kinetics cannot be left out of any discussion of the rational basis of chemotherapy. When clinical oncologists began to apply cell kinetic concepts in practice about 15 years ago, the theoretical basis was still very poor, in spite of Skipper's pro...

  17. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.

    Science.gov (United States)

    Chao, Xu; Zhang, Zhuoli; Guo, Lili; Zhu, Jingjing; Peng, Mingli; Vermorken, Alphonsus J M; Van de Ven, Wim J M; Chen, Chao; Cui, Yali

    2012-01-01

    Magnetic nanoparticles (NPs) loaded with antitumor drugs in combination with an external magnetic field (EMF)-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1) to investigate application of PEG modified GMNPs (PGMNPs) as a drug carrier of the chemotherapy compound doxorubicin (DOX) in vitro; 2) to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs) using an EMF-guided delivery in vivo. First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues) was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M). The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each pchemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.

  18. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Steven H., E-mail: shlin@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Myles, Bevan [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guo Xiaomao [Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Palmer, Matthew [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G.; Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-07-01

    Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test. Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical

  19. Troglitazone reverses the multiple drug resistance phenotype in cancer cells

    Directory of Open Access Journals (Sweden)

    Gerald F Davies

    2009-03-01

    Full Text Available Gerald F Davies1, Bernhard HJ Juurlink2, Troy AA Harkness11Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada; 2College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi ArabiaAbstract: A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1 and histone H3 expression. The thiazolidinedione troglitazone (TRG downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX. The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp drug efflux pump multiple drug resistance protein 1 (MDR-1, and the breast cancer resistance protein (BCRP. TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers. Keywords: chemotherapy, doxorubicin, breast cancer resistance protein-1, multiple drug resistance, multiple drug resistance protein 1

  20. Endocrine Resistance in Breast Cancer

    Directory of Open Access Journals (Sweden)

    J. M. Dixon

    2014-01-01

    Full Text Available Around 70% of all breast cancers are estrogen receptor alpha positive and hence their development is highly dependent on estradiol. While the invention of endocrine therapies has revolusioned the treatment of the disease, resistance to therapy eventually occurs in a large number of patients. This paper seeks to illustrate and discuss the complexity and heterogeneity of the mechanisms which underlie resistance and the approaches proposed to combat them. It will also focus on the use and development of methods for predicting which patients are likely to develop resistance.

  1. Neoadjuvant chemotherapy in patients with locally advanced breast cancer: A pilot-observational study

    Directory of Open Access Journals (Sweden)

    Hardik G Dodiya

    2015-01-01

    Full Text Available Background: Locally advanced breast cancer (LABC remains major clinical issue with regard to selection and duration of therapy since many years. Neoadjuvant chemotherapy (NACT is multimodality program, established to treat LABC. Many research tasks are ongoing to develop specific neoadjuvant chemotherapy regimen with specific duration to improve long-term control of LABC. Patients and Methods: Forty-seven patients diagnosed with LABC were Included and analyzed to compare the outcomes [pathological complete response (pCR, clinical response, overall response rate (ORR, disease control rate, overall survival and progression-free survival]. These patients treated with either combination of anthracycline and taxane-based chemotherapy or anthracycline-based chemotherapy. Results: There was no any statistical significance with respect to demographic data treated of patients between two arms (P > 0.05. Patients underwent TAC chemotherapy had pCR 20.8% whereas FAC/FEC chemotherapy patients had pCR 13% (P = 0.48. Higher ORR was noted in TAC chemotherapy arm (75% when compared with FAC/FEC chemotherapy arm (60.9% (P = 0.29. The study also shows better disease control rate in TAC chemotherapy arm (95.8% as compared to FAC/FEC chemotherapy arm (82.6%. There was no statistical significance in overall survival (P = 0.31 and progression-free survival (P = 0.51 between two arms. Conclusion: Despite of the superiority of combination of anthracycline and taxane-based chemotherapy over the anthracycline-based chemotherapy in the present study, further pivotal studies should be conducted to confirm the combination of anthracycline and taxane-based chemotherapy as a better neoadjuvant regimen for treatment of LABC tumors.

  2. Chemotherapy in Children with Head and Neck Cancers: Perspectives and Review of Current Therapies.

    Science.gov (United States)

    Choi, Daniel K; Schmidt, Mary Lou

    2016-02-01

    Cancers of the head and neck in children represent a heterogeneous group of malignancies requiring a variety of treatment modalities. In many instances of childhood head and neck cancers, chemotherapy will be required for treatment, often in conjunction with surgery and/or radiation therapy. Chemotherapy in children with head and neck cancers poses unique challenges in terms of immediate as well as long-term toxicities. This article focuses on the common chemotherapeutic agents, with a particular focus on early and late effects, used in the treatment of children with head and neck cancers. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy.

    Science.gov (United States)

    Chen, Helen H W; Chen, Wen-Chung; Liang, Zhang-Dong; Tsai, Wen-Bin; Long, Yan; Aiba, Isamu; Fu, Siqing; Broaddus, Russell; Liu, Jinsong; Feun, Lynn G; Savaraj, Niramol; Kuo, Macus Tien

    2015-01-01

    Platinum (Pt)-based antitumor agents remain important chemotherapeutic agents for treating many human malignancies. Elevated expression of the human high-affinity copper transporter 1 (hCtr1), resulting in enhanced Pt drug transport into cells, has been shown to be associated with improved treatment efficacy. Thus, targeting hCtr1 upregulation is an attractive strategy for improving the treatment efficacy of Pt-based cancer chemotherapy. Regulation of hCtr1 expression by cellular copper homeostasis is discussed. Association of elevated hCtr1 expression with intrinsic sensitivity of ovarian cancer to Pt drugs is presented. Mechanism of copper-lowering agents in enhancing hCtr1-mediated cis-diamminedichloroplatinum (II) (cisplatin, cDDP) transport is reviewed. Applications of copper chelation strategy in overcoming cDDP resistance through enhanced hCtr1 expression are evaluated. While both transcriptional and post-translational mechanisms of hCtr1 regulation by cellular copper bioavailability have been proposed, detailed molecular insights into hCtr1 regulation by copper homeostasis remain needed. Recent clinical study using a copper-lowering agent in enhancing hCtr1-mediated drug transport has achieved incremental improvement in overcoming Pt drug resistance. Further improvements in identifying predictive measures in the subpopulation of patients that can benefit from the treatment are needed.

  4. Diabetes alone should not be a reason for withholding adjuvant chemotherapy for stage III colon cancer.

    Science.gov (United States)

    van Waalwijk, Maren A; van de Schans, Saskia A M; Haak, Harm R; Extermann, Martine; Dercksen, Wouter M W; Janssen-Heijnen, Maryska L G

    2011-01-01

    With increasing prevalence of diabetes mellitus and colon cancer, the number of patients suffering from both diseases is growing, and physicians are being faced with complicated treatment decisions. To investigate the association between diabetes and treatment/course of stage III colon cancer and the association between colon cancer and course of diabetes. Additional information was collected from the medical records of all patients with both stage III colon cancer and diabetes ( n =201) and a random sample of stage III colon cancer patients without diabetes ( n =206) in the area of the population-based Eindhoven Cancer Registry (1998-2007). Colon cancer patients without diabetes were more likely to receive adjuvant chemotherapy compared with diabetic colon cancer patients (OR 1.8; 95% CI 1.2-2.7). After adjustment for age, this difference was borderline significant (OR 1.6; 95% CI 1.0-2.6). Diabetic patients did not have: significantly more side-effects from surgery or adjuvant chemotherapy; more recurrence from colon cancer; significantly shorter time interval until recurrence; or a poorer disease-free survival or overall survival. Age and withholding of adjuvant chemotherapy were most predictive of all-cause mortality. After colon cancer diagnosis, the dose of antiglycaemic medications was increased in 22% of diabetic patients, resulting in significantly lower glycaemic indexes than before colon cancer diagnosis. Since diabetic patients did not have more side-effects of adjuvant chemotherapy, and adjuvant chemotherapy had a positive effect on survival for both patients with and without diabetes, diabetes alone should not be a reason for withholding adjuvant chemotherapy. Journal of Comorbidity 2011;1:19-27.

  5. Reirradiation of recurrent breast cancer with and without concurrent chemotherapy

    Directory of Open Access Journals (Sweden)

    Kretschmer Matthias

    2008-09-01

    Full Text Available Abstract Background Treatment options for loco-regional recurrent breast cancer after previous irradiation are limited. The efficacy of chemotherapy might be hampered because of impaired tissue perfusion in preirradiated tissue. Thus, mastectomy or local excision and reconstructive surgery are the preferred treatments. However, in recent years evidence accumulates that a second breast conserving approach with reirradiation as part of the treatment might be feasible and safe and, furthermore, reirradiation might be an option for palliation. Here we report on the experience of a single community centre in reirradiation of recurrent breast cancer. Methods The report is based on 29 patients treated with reirradiation. All data were prospectively collected. The median age was 63 years (range 35 to 82 yrs. The interval between initial diagnosis and diagnosis before start of reirradiation was 11.6 months to 295.5 months. The mean total dose (initial dose and reirradiation dose was 106.2 Gy (range 80.4 to 126 Gy and the mean BED3 Gy 168,5 Gy (range 130,6 to 201,6. The mean interval between initial radiotherapy and reirradiation was 92.9 months (range 8.7 to 290.1. Inoperable or incompletely resected patients were offered concurrent chemotherapy with either 5-FU or capecitabine. All patients received 3D-conformal radiotherapy with 1.6 to 2.5 Gy/fraction five times weekly. The treatment volume comprised all visible lesions or lesions detectable on CT/MRI/FDG-PET/CT or the tumour bed or recurrent tumour. Results The local progression-free survival of all patients at one and two years was 81% and 63%. Patients who had no surgery of the recurrence (16/29 had local progression-free survival at one and two years of 72% and 25% with a median progression-free survival time of 17 months. Partial remission and good symptom relief was achieved in 56% (9/16 or complete response of symptoms and/or tumour in 44% (7/16. Patients who had no distant metastases and had at

  6. Focal adhesion signaling and therapy resistance in cancer.

    Science.gov (United States)

    Eke, Iris; Cordes, Nils

    2015-04-01

    Interlocking gene mutations, epigenetic alterations and microenvironmental features perpetuate tumor development, growth, infiltration and spread. Consequently, intrinsic and acquired therapy resistance arises and presents one of the major goals to solve in oncologic research today. Among the myriad of microenvironmental factors impacting on cancer cell resistance, cell adhesion to the extracellular matrix (ECM) has recently been identified as key determinant. Despite the differentiation between cell adhesion-mediated drug resistance (CAMDR) and cell adhesion-mediated radioresistance (CAMRR), the underlying mechanisms share great overlap in integrin and focal adhesion hub signaling and differ further downstream in the complexity of signaling networks between tumor entities. Intriguingly, cell adhesion to ECM is per se also essential for cancer cells similar to their normal counterparts. However, based on the overexpression of focal adhesion hub signaling receptors and proteins and a distinct addiction to particular integrin receptors, targeting of focal adhesion proteins has been shown to potently sensitize cancer cells to different treatment regimes including radiotherapy, chemotherapy and novel molecular therapeutics. In this review, we will give insight into the role of integrins in carcinogenesis, tumor progression and metastasis. Additionally, literature and data about the function of focal adhesion molecules including integrins, integrin-associated proteins and growth factor receptors in tumor cell resistance to radio- and chemotherapy will be elucidated and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

    Science.gov (United States)

    Kimura, Go; Ueda, Takeshi

    2017-03-01

    A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

  8. Understanding breast cancer patients' preference for two types of exercise training during chemotherapy in an unblinded randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Vallance Jeffrey K

    2008-10-01

    Full Text Available Abstract Background Patient preference for group assignment may affect outcomes in unblinded trials but few studies have attempted to understand such preferences. The purpose of the present study was to examine factors associated with breast cancer patients' preference for two types of exercise training during chemotherapy. Methods Breast cancer patients (N = 242 completed a battery of tests including a questionnaire that assessed patient preference and the theory of planned behavior (TPB prior to being randomized to usual care, resistance exercise training (RET, or aerobic exercise training (AET. Results 99 (40.9% participants preferred RET, 88 (36.4% preferred AET, and 55 (22.7% reported no preference. Past exercisers (p = 0.023, smokers (p = 0.004, and aerobically fitter participants (p = 0.005 were more likely to prefer RET. As hypothesized, participants that preferred AET had more favorable TPB beliefs about AET whereas participants that preferred RET had more favorable TPB beliefs about RET. In multivariate modeling, patient preference for RET versus AET was explained (R2 = .46; p 2 = .48; p Conclusion Breast cancer patients' preference for RET versus AET during chemotherapy was predicted largely by a difference in motivation for each type of exercise which, in turn, was based on differences in their beliefs about the anticipated benefits, enjoyment, and difficulty of performing each type of exercise during chemotherapy. These findings may help explain patient preference effects in unblinded behavioral trials. Trial Registration ClinicalTrials.gov Identifier NCT00115713.

  9. Body weight and composition changes in ovarian cancer patients during adjuvant chemotherapy.

    Science.gov (United States)

    Gil, Karen M; Frasure, Heidi E; Hopkins, Michael P; Jenison, Eric L; von Gruenigen, Vivian E

    2006-10-01

    To prospectively examine body weight changes in women with newly diagnosed ovarian cancer receiving surgery and adjuvant chemotherapy. Body composition was examined in a subset of these women. Body weight (BW) and body composition, using bioelectrical impedance (RJL Systems Inc.), were prospectively measured pre- and post-operatively, and at 3, 6, and 12 months. Mean age of 42 women was 59 years and did not differ by stage of disease. Nine women with early stage disease did not receive adjuvant chemotherapy. Mean BW of 33 patients receiving chemotherapy decreased from the pre- to post-operative visit and then returned to baseline levels by 12 months (F = 8.70, P = 0.003). Nine patients who did not receive chemotherapy demonstrated a similar pattern (F = 7.0, P = 0.002). Women receiving chemotherapy with stage I/II cancer had a 2.8 +/- 2.0 kg weight gain over the year, and women with stage III/IV cancer had a 1.5 +/- 1.5 kg weight loss (t = 1.72, P = 0.096). A subset of women with stage I/II (n = 6) and stage III/IV (n = 6) ovarian cancer receiving chemotherapy had body composition measured at three time points. Absolute body fat changes paralleled changes in BW (F = 9.95, P = 0.002). Our study is the first prospective evaluation of body weight and composition in women undergoing surgery and chemotherapy for ovarian cancer. These results demonstrate that women undergoing surgery for ovarian cancer lost weight following surgery and regained it slowly over the following year. Further investigations of weight changes during adjuvant chemotherapy are indicated to assess potential changes in different stages of disease.

  10. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    Science.gov (United States)

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age Improved and clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; Pchemotherapy regimens. In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

  11. Laparoscopy mitigates adverse oncological effects of delayed adjuvant chemotherapy for colon cancer.

    Science.gov (United States)

    Gantt, Gerald A; Ashburn, Jean; Kiran, Ravi P; Khorana, Alok A; Kalady, Matthew F

    2015-02-01

    Delaying initiation of adjuvant chemotherapy more than 8 weeks after surgical resection for colorectal cancer adversely affects overall patient survival. The effect of a laparoscopic surgical approach on initiation of chemotherapy has not been studied. The goal of this study was to determine if a laparoscopic approach to colon cancer resection affects the timing of adjuvant chemotherapy and outcomes. Patients who underwent curative surgery for stage II or III colon cancer and received adjuvant chemotherapy between 2003 and 2010 were identified from a prospectively maintained database. Patients were categorized according to surgical approach: open or laparoscopic. Patient demographics, clinicopathologic variables, postoperative complications, time from surgery to initiation of chemotherapy, and long-term oncologic outcomes were compared. Age, gender, ASA class, BMI, tumor stage, and postoperative complications were similar for laparoscopic and open cases, while length of stay was 2 days shorter for laparoscopic cases (5.4 vs 7.6 days, p < 0.01). The proportion of patients who received adjuvant chemotherapy more than 8 weeks after surgery did not differ between the groups (35.6 % open vs 38.7 % laparoscopic, p = 0.77). In the open group, delay in chemotherapy after surgery was associated with decreased disease-free and overall survival (p = 0.01, 0.01, respectively). However, delay in chemotherapy more than 8 weeks did not affect disease-free or overall survival in the laparoscopy group (p = 0.93, 0.51, respectively). The benefits of quicker recovery after laparoscopic surgery did not translate into earlier initiation of adjuvant chemotherapy in this retrospective study. However, a laparoscopic approach negated the inferior oncologic outcomes of patients who received delayed initiation of chemotherapy.

  12. Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and anthracycline exposed breast cancer

    NARCIS (Netherlands)

    Faneyte, Ian F.; Kristel, Petra M. P.; van de Vijver, Marc J.

    2004-01-01

    BACKGROUND: Multidrug resistance associated proteins MRP1, MRP2 and MRP3 confer in vitro multidrug resistance. We investigated their role in breast cancer resistance to anthracycline-based chemotherapy. MATERIALS AND METHODS: Using real-time reverse transcriptase polymerase chain reaction (RT-PCR)

  13. Correlation between chemotherapy resistance in osteosarcoma patients and PAK5 and Ezrin gene expression.

    Science.gov (United States)

    Liu, Qian; Xu, Bo; Zhou, Wanshan

    2018-01-01

    The correlation between PAK5 (P21-activated kinase 5) and Ezrin gene expression and chemotherapy resistance of osteosarcoma patients was investigated. The cisplatin (CDDP)-resistance model of osteosarcoma cells SOSP-9607/CDDP was established to detect the cell growth curve. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the drug resistance of cells to chemotherapy drugs. Transwell assay was used to detect the invasive capacity of cells. Semi-quantitative PCR (qPCR) was used to detect the mRNA expression levels in the drug resistance-related genes PAK5 and Ezrin. Western blot analysis was used to detect the protein expression levels in PAK5 and Ezrin. Tumor tissues were taken from the osteosarcoma patients with chemotherapy resistance to detect the expression levels of PAK5 and Ezrin via immunohistochemical detection, and the correlation between PAK5 and Ezrin expressions was studied. The results of MTT assay showed that the growth rate of SOSP-9607 was similar to that of SOSP-9607/CDDP, and the difference was not statistically significant (P>0.05). The sensitivity of SOSP-9607 to CDDP was significantly higher than that of SOSP-9607/CDDP, and the difference was statistically significant (Presistance cell lines of osteosarcoma were constructed successfully. Semi-qPCR and western blot analysis showed that the protein expression levels in PAK5 and Ezrin in SOSP-9607/CDDP were significantly higher than those in SOSP-9607 (Presistance is closely related to the expression levels of PAK5 and Ezrin genes. Thus, PAK5 and Ezrin genes may affect the tolerance of osteosarcoma patients to chemotherapy drugs during treatment via the synergistic effect.

  14. Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

    Directory of Open Access Journals (Sweden)

    Murugesan Manoharan

    2006-10-01

    Full Text Available OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC with orthotopic neobladder (NB to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

  15. Hematologic safety of breast cancer chemotherapies in patients with hepatitis B or C virus infection.

    Science.gov (United States)

    Shoji, Hirokazu; Hashimoto, Kenji; Kodaira, Makoto; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Tamura, Kenji; Ando, Masashi; Fujiwara, Yasuhiro

    2012-01-01

    Information regarding hematological toxicities in breast cancer chemotherapy patients with hepatitis B (HBV) or C virus (HCV) infection is limited. We retrospectively reviewed the presence of hepatotoxicities (i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin elevation) and hematotoxicities (i.e. leukopenia and thrombocytopenia) among breast cancer patients with HBV or HCV infection who received chemotherapy from 1999 to 2010. All of the patients included in this analysis were classified as Child-Pugh A. Among 32 patients with HBV infection who underwent chemotherapy (total cycles, 378), 3 experienced grade 3/4 hepatotoxicities, requiring 2 treatment delays and 1 treatment revision. Further, 9 patients experienced grade 3/4 hematotoxicities; of these, 2 required treatment delays and 3 required treatment revisions. Fifty-two HCV patients underwent a total of 570 cycles of chemotherapy. Five patients experienced grade 3/4 hepatotoxicities and required treatment delays, whereas 10 patients experienced grade 3 hematotoxicities; 3 of these patients required treatment delays. Hematotoxicities requiring chemotherapy dose or treatment revision were not highly prevalent among breast cancer chemotherapy patients with HBV or HCV infection and a normal range of liver function. Under careful monitoring, chemotherapy dosage or schedule adjustments may not be necessary in similar patients positive for HBV or HCV. Copyright © 2012 S. Karger AG, Basel.

  16. Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study

    Science.gov (United States)

    Neugut, Alfred I.; Hillyer, Grace Clarke; Kushi, Lawrence H.; Lamerato, Lois; Leoce, Nicole; Nathanson, S. David; Ambrosone, Christine B.; Bovbjerg, Dana H.; Mandelblatt, Jeanne S.; Magai, Carol; Tsai, Wei Yann; Jacobson, Judith S.; Hershman, Dawn L.

    2012-01-01

    Purpose For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. Patients and Methods We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. Results Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor– and progesterone receptor–negative status) were associated with increased chemotherapy initiation. Conclusion Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few

  17. TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

    Science.gov (United States)

    Li, Changfeng; Gao, Yongjian; Li, Yongchao; Ding, Dayong

    2017-09-16

    Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis. Copyright © 2017. Published by Elsevier Inc.

  18. Weight change trajectory in women with breast cancer receiving chemotherapy and the effect of different regimens.

    Science.gov (United States)

    Liu, Li-Ni; Wen, Fur-Hsing; Miaskowski, Christine; Lin, Yung-Chang; Wang, Jong-Shyan; Jeng, Chii; Chen, Mei-Ling

    2014-10-01

    To investigate the trajectory of weight change in Taiwanese women with breast cancer after starting chemotherapy and the impact of chemotherapy regimens on weight change while controlling for age, menopausal status, body mass index, lymph node involvement and changes in habits of dietary fat intake and exercise. Weight gain after adjuvant chemotherapy in women with breast cancer has negative impact on health outcomes. Longitudinal, clinical observational study. Weights were repeatedly measured in 147 women with breast cancer stages I-III. Hierarchical linear modelling was used to analyse these longitudinal data. The overall pattern of weight change was a cubic form beginning with a mean of 56·9 kg before chemotherapy. It gradually increased to 59·4 kg at 8·5 months after the first chemotherapy followed by a decrease to 58·5 kg at 21·5 months. During the last 2·5 months, weight increased slightly and never returned to the initial level. After controlling for confounders, steeper weight change was observed among women receiving cyclophosphamide, methotrexate and fluorouracil. The highest weight gain in the cyclophosphamide, methotrexate and fluorouracil group was 2·9 kg (5%) vs. 0·9 kg (1%) in the anthracycline-based group. The trajectory of body weight change within two years after chemotherapy shows a trend of gradual ascent, followed by a small decline and a slight increase in the last 2·5 months. The chemotherapy regimen can predict the trend after controlling for other confounders; women on cyclophosphamide, methotrexate and fluorouracil have a steeper weight change. Nurses can inform women with breast cancer about the expected changes in body weight after chemotherapy to reduce their uncertainty. Future studies on effective interventions to minimise chemotherapy-induced weight gain are needed. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells.

    Science.gov (United States)

    Berkovich, Liron; Earon, Gideon; Ron, Ilan; Rimmon, Adam; Vexler, Akiva; Lev-Ari, Shahar

    2013-08-19

    Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.

  1. MicroRNAs Change the Landscape of Cancer Resistance.

    Science.gov (United States)

    Zhu, Jun; Zhu, Wei; Wu, Wei

    2018-01-01

    One of the major challenges in the cancer treatment is the development of drug resistance. It represents a major obstacle to curing cancer with constrained efficacy of both conventional chemotherapy and targeted therapies, even recent immune checkpoint blockade therapy. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in the resistance to various cancer treatments. MicroRNAs are a family of small noncoding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified in human genome. While one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance, thereby modulating the sensitivity of cancer cells to treatment. Therefore, manipulation of miRNAs may be an attractive strategy for more effective individualized therapies through reprograming resistant network in cancer cells.

  2. Anxiety and coping in women with breast cancer in chemotherapy.

    Science.gov (United States)

    Silva, Araceli Vicente da; Zandonade, Eliana; Amorim, Maria Helena Costa

    2017-06-05

    to identify the coping strategies used by women with breast cancer in chemotherapy and to verify the association with the anxiety profile presented by them. cross-sectional study of the analytical type. We used a random sample of 307 women with cancer in previous chemotherapy, adjuvant or palliative treatment. The data was collected using an interview technique with form registration, active search in medical records, Scale of Mode of Confronting Problems and Inventory of Anxiety and State. The Statistical Package for Social Sciences 19.0, Pearson correlation coefficient and the test Mann-Whitney were used. there was a significant association of the anxiety trait and problem-focused coping strategies with a focus on emotion (pansiedade por elas apresentado. estudo de corte transversal do tipo analítico. Utilizou-se amostra aleatória de 307 mulheres com câncer em tratamento quimioterápico prévio, adjuvante ou paliativo. Coletou-se os dados com técnica de entrevista com registro em formulário, busca ativa nos prontuários, Escala de Modo de Enfrentamento de Problemas e Inventário de Ansiedade e Estado. Utilizou-se para análise o Pacote Estatístico para Ciências Sociais 19.0, coeficiente de correlação de Pearson e o teste Mann-Whitney. existiu associação significante do traço de ansiedade e as estratégias de enfrentamento com foco no problema e com foco na emoção (pansiedade com o enfrentamento com foco no problema (p=0,001) e com o foco na emoção (p=0,004). Os resultados demonstram fracas associações entre as diferentes estratégias de enfrentamento. a estratégia de enfrentamento eleita pelas mulheres com câncer de mama tem relação direta com a ansiedade. As pacientes que possuem ansiedade com nível baixo tendem a utilizar como estratégia a resolução dos problemas e quando o nível é médio a alto o enfrentamento com foco na emoção. identificar las estrategias de enfrentamiento utilizadas por las mujeres con cáncer de mama sometidas

  3. Shenyi Capsule () plus chemotherapy versus chemotherapy for non-small cell lung cancer: A systematic review of overlapping meta-analyses.

    Science.gov (United States)

    Guo, Xiu-Wei; Hu, Nai-Dong; Sun, Gui-Zhi; Li, Meng; Zhang, Pei-Tong

    2017-10-18

    To assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence by performing a systematic review of overlapping meta-analyses regarding Shenyi Capsule (, SC) plus chemotherapy versus chemotherapy of non-small cell lung cancer (NSCLC). A literature search was conducted to select systematic reviews comparing SC plus chemotherapy with chemotherapy for NSCLC. Meta-analyses only composed of randomized controlled trials (RCTs) met the inclusion criteria. Two authors individually estimated the quality of meta-analysis and extracted data. The Jadad decision algorithm was applied to guarantee which meta-analysis provided the best original evidence. A total of 5 meta-analyses were included. All the studies composed of RCTs or quasi-RCTs and were regarded as level-II evidence. The scores of the Assessment of Multiple Systematic Reviews ranged from 3 to 6 (median 4). A high-quality meta-analysis with more RCTs was chosen, which suggested that SC plus chemotherapy could increase incidence of short-term efficacy, improve the quality of life and survival rate in comparison to chemotherapy. However, there was no statistically significant difference between SC plus chemotherapy and chemotherapy regarding chemotherapy-induced side effect, such as liver and kidney function obstacle, leukopenia, hemoglobin decrement and gastrointestinal adverse reaction. Based on the best available evidence, treatment effect of SC plus chemotherapy was better than chemotherapy and did not increase side effects. Therefore, SC plus chemotherapy may be superior to chemotherapy for treating NSCLC. However, due to some limitations, SC plus chemotherapy should be cautiously considered, and further high-quality meta-analyses are needed.

  4. Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun [Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081 (China); Tan, Wenhua, E-mail: tanwenhua1962@163.com [Department of Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086 (China)

    2015-10-23

    Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

  5. Targeting Intracellular Calcium Signaling ([Ca2+]i to Overcome Acquired Multidrug Resistance of Cancer Cells: A Mini-Overview

    Directory of Open Access Journals (Sweden)

    Dietrich Büsselberg

    2017-05-01

    Full Text Available Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca2+]i signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs. We propose that [Ca2+]i signaling modulates gene expression of multidrug resistant (MDR genes which in turn can be modulated by epigenetic factors which in turn leads to modified protein expression in drug resistant tumor cells. A precise knowledge of these mechanisms will help to develop new therapeutic strategies for drug resistant tumors and will improve current chemotherapy.

  6. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer

    OpenAIRE

    Palmela, Carolina; Velho, S?nia; Agostinho, Lisa; Branco, Francisco; Santos, Marta; Santos, Maria Pia Costa; Oliveira, Maria Helena de; Strecht, Jo?o; Maio, Rui; Cravo, Mar?lia; Baracos, Vickie E.

    2017-01-01

    Purpose Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity...

  7. The effects of a six-week supervised multimodal exercise intervention during chemotherapy on cancer-related fatigue

    DEFF Research Database (Denmark)

    Andersen, Christina; Rørth, Mikael; Ejlertsen, Bent

    2013-01-01

    Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objective...... of this study is to evaluate whether a six-week supervised multimodal exercise intervention, adjunct to chemotherapy and standard care, can reduce the patient's CRF level....

  8. Using Oncology Nursing Society Cancer Chemotherapy Guidelines as a basis for continuing education in rural hospitals.

    Science.gov (United States)

    Williams, S A

    1995-05-01

    To describe a workshop developed to teach nurses caring for patients with cancer in a southern, rural area how to administer chemotherapy in an inpatient or homecare setting. The Oncology Nursing Society (ONS) Cancer Chemotherapy Guidelines and published articles and books. An oncology clinical nurse specialist teaching at a local university developed and presented 10 hours of didactic content and a 6-hour clinical practicum. The workshop was conducted in association with a community hospital, which offered oncology care to patients with cancer in the community. All nurses who successfully completed the workshop demonstrated improved ability in caring for patients with cancer and in administering chemotherapy. The ONS Cancer Chemotherapy Guidelines provided an excellent outline for the development of an initial course on the science of chemotherapy and management of related symptoms. Many nurses work in rural areas where they are expected to provide competent nursing care to a variety of specialized patient populations, yet they have limited access to educational opportunities. A workshop format is feasible and can provide the education necessary for nurses who care for patients with cancer.

  9. [Jejunostomy catheter feeding during postoperative chemotherapy for Stage IV gastric cancer].

    Science.gov (United States)

    Matsuyama, Jin; Fukushima, Yukio; Toshiyama, Reishi; Takeda, Mitsunobu; Tokuoka, Masayoshi; Ide, Yoshihito; Hashimoto, Kazuhiko; Yokoyama, Shigekazu; Morimoto, Takashi; Nomura, Takashi; Kodama, Ken; Sasaki, Yo

    2013-11-01

    Chemotherapy followed by surgery for Stage IV gastric cancer with passage obstruction poses a problem in terms of poor postoperative nutritional status. By maintaining an adequate postoperative nutrition status with jejunostomy catheter feeding, chemotherapy may possibly be continued. We treated 40 cases of Stage IV gastric cancer with passage obstruction from January 2008 to December 2011. In every case, jejunostomy catheter feeding tubes were placed during gastric cancer surgery. We performed 13 total gastrectomies, 20 distal gastrectomies, and 7 gastrojejunal bypass surgeries. Tube obstruction in 4 cases( 10%) and tube deviation in 1 case( 2.5%) occurred during the tube feeding period. Chemotherapy could be resumed in 37 cases( 92.5%), and the duration of chemotherapy was 330 days( range, 41-721). In cases of Stage IV gastric cancer, patients are obliged to start postoperative chemotherapy at an unstable period. By starting jejunal catheter feeding at an early stage after surgery, improved results could be expected in terms of shortening of the hospital stay or continuation of chemotherapy.

  10. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

    Science.gov (United States)

    Bos, A C R K; van Erning, F N; van Gestel, Y R B M; Creemers, G J M; Punt, C J A; van Oijen, M G H; Lemmens, V E P P

    2015-11-01

    Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus colon cancer patients within 8 weeks post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Efficacy of Adjuvant Chemotherapy and Prognostic Factors for Patients with Extrahepatic Bile Duct Cancer.

    Science.gov (United States)

    Lee, Hee Seung; Lee, Sang Hoon; Roh, Yun Ho; Chung, Moon Jae; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Chung, Jae Bok; Bang, Seungmin

    2016-01-01

    Surgical resection is the only curative treatment for extrahepatic bile duct cancer. Additionally, the recurrence rate after curative surgery is relatively high, requiring adjuvant therapy. However, the efficacy of adjuvant chemotherapy compared with surgery alone has not yet been clarified. This study aimed to evaluate the efficacy of adjuvant chemotherapy and identify prognostic factors influencing survival in extrahepatic bile duct cancer patients who underwent curative surgical resection. Ninety-seven patients with extrahepatic bile duct cancer who underwent curative resection between January 2005 and December 2010 were retrospectively analyzed. Among the 97 patients, 31 underwent adjuvant chemotherapy and 66 did not. The 5-year overall survival rate was 34% for patients who underwent adjuvant chemotherapy. There was no significant difference for overall survival between patients who underwent adjuvant chemotherapy and those who did not (p = 0.228). On multivariate analysis, postoperative carbohydrate antigen 19-9 levels and histologic grade were independent prognostic factors related to long-term survival (p chemotherapy did not improve survival after surgical resection for extrahepatic bile duct cancer. © 2016 S. Karger AG, Basel.

  12. Motivation to uphold physical activity in women with breast cancer during adjuvant chemotherapy treatment.

    Science.gov (United States)

    Wilhelmsson, Anna; Roos, Maria; Hagberg, Lars; Wengström, Yvonne; Blomberg, Karin

    2017-08-01

    Physical activity (PA) is important for recovery after a breast cancer diagnosis; however, women's motivation to engage in PA can be impacted by disease and/or treatment, and can therefore be a challenge. This study explored factors associated with PA levels during chemotherapy among women with breast cancer. The study had a cross-sectional descriptive and comparative design using a study-specific questionnaire. One hundred women with breast cancer receiving adjuvant chemotherapy were included. Data were analysed by Pearson's correlation coefficient and linear regression. The open question was subjected to manifest content analysis. Identified factors associated with engaging in PA during chemotherapy treatment were: being physically active before diagnosis, and the information given by the oncology nurse before the treatment start. The physically active women experienced higher psychological wellbeing, less fatigue, and faster recovery after treatment. They also experienced an overall feeling of fitness. It seems that PA is associated with less fatigue, better recovery between chemotherapy treatments, and a better mental condition leading to wellbeing. Information given by the oncology nurse may be an important factor for being physically active. Women with breast cancer need to get specific advice about and support in engaging in PA to feel better during chemotherapy treatment. Further research is required to develop guidelines for advice about and support regarding PA during chemotherapy treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Nutritional status and quality of life of cancer patients needing exclusive chemotherapy: a longitudinal study.

    Science.gov (United States)

    Salas, Sebastien; Mercier, Sophie; Moheng, Benjamin; Olivet, Sandrine; Garcia, Marie-Eve; Hamon, Sophie; Sibertin-Blanc, Camille; Duffaud, Florence; Auquier, Pascal; Baumstarck, Karine

    2017-04-27

    The aims of this study were to report nutritional status in a large panel of patients with cancer requiring exclusive chemotherapy and to study the influence of nutritional status on their quality of life (QoL). This work was a longitudinal cohort study performed at a French university teaching hospital. Eligible patients were individuals with a cancer needing treatment based on exclusive chemotherapy. Three work-ups were performed: i) before the administration of the first course of chemotherapy: T1, ii) before the administration of the second (for patients with 3 planned courses) or third (patients with 6 planned courses) course: T2, and iii) before the administration of the last planned course: T3. The following data were collected: general health (performance status) and nutritional status (weight, anorexia grading, albuminemia, pre-albuminemia, and C-reactive protein) and QoL. The nutritional status of patients with cancer was preserved. Functional impairment, the presence of anorexia, the palliative nature of the chemotherapy, and an elevated C-reactive protein dosage were independent predictive factors of a lower QoL among patients assessed at the end of chemotherapy. Although larger studies should corroborate these findings, clinicians may include this information in the management of patients with cancer requiring exclusive chemotherapy to identify the most vulnerable patients. Current controlled trials NCT01687335 (registration date: October 6, 2011).

  14. Surgery and Adjuvant Chemotherapy Use Among Veterans With Colon Cancer: Insights From a California Study

    Science.gov (United States)

    Hynes, Denise M.; Tarlov, Elizabeth; Durazo-Arvizu, Ramon; Perrin, Ruth; Zhang, Qiuying; Weichle, Thomas; Ferreira, M. Rosario; Lee, Todd; Benson, Al B.; Bhoopalam, Nirmala; Bennett, Charles L.

    2010-01-01

    Purpose US veterans have been shown to be a vulnerable population with high cancer rates, and cancer care quality in Veterans Affairs (VA) hospitals is the focus of a congressionally mandated review. We examined rates of surgery and chemotherapy use among veterans with colon cancer at VA and non-VA facilities in California to gain insight into factors associated with quality of cancer care. Methods A retrospective cohort of incident colon cancer patients from the California Cancer Registry, who were ≥ 66 years old and eligible to use VA and Medicare between 1999 and 2001, were observed for 6 months after diagnosis. Results Among 601 veterans with colon cancer, 72% were initially diagnosed and treated in non-VA facilities. Among veterans with stage I to III cancer, those diagnosed and initially treated in VA facilities experienced similar colectomy rates as those at non-VA facilities. Stage III patients diagnosed and initially treated in VA versus non-VA facilities had similar odds of receiving adjuvant chemotherapy. In both settings, older patients had lower odds of receiving chemotherapy than their younger counterparts even when race and comorbidity were considered (age 76 to 85 years: odds ratio [OR] = 0.18; 95% CI, 0.07 to 0.46; age ≥ 86 years: OR = 0.17; 95% CI, 0.04 to 0.73). Conclusion In California, older veterans with colon cancer used both VA and non-VA facilities for cancer treatment, and odds of receiving cancer-directed surgery and chemotherapy were similar in both systems. Among stage III patients, older age lowered odds of receiving adjuvant chemotherapy in both systems. Further studies should continue to explore potential health system effects on quality of colon cancer care across the United States. PMID:20406940

  15. Efficacy of chemotherapy after hormone therapy for hormone receptor–positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ryutaro Mori

    2014-11-01

    Full Text Available Objective: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases. Methods: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. Results: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+ status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%. A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%. The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085. However, there were no significant differences in the response to or duration of chemotherapy. Conclusion: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype

  16. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    Science.gov (United States)

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS but not with OS. PMID:27293986

  17. Routine Hemostasis and Hemogram Parameters: Valuable Assessments for Coagulation Disorder and Chemotherapy in Cancer Patients.

    Science.gov (United States)

    Zhu, Ying-Wei; Feng, Tong-Bao; Zhou, Xian-Ju; Hu, Xue-Li; Ding, Jie; Zhu, Wen-Yu; Qian, Dan-Ping; Sun, Yi-Wu

    2016-08-05

    The clotting system abnormalities are the common complication in cancer patients. The aim of this retrospective study was to evaluate the coagulation state, clinical features, and treatment in cancer patients by routine tests. A total of 2328 patients with different types of cancer were classified as the positive group (n = 1419, including 53 patients with thrombosis) and the negative group (n = 909) based on D-dimer (DD) value. Of the 2328 cases, 354 were admitted for chemotherapy. Hemostasis test and complete blood count (CBC) were performed during treatment or following-up. This study showed that the hypercoagulable state was affected not only by clinical staging (P cancer patients was moderated 2-3 weeks after chemotherapy (P < 0.05 for first six cycles). The routine hemostatic parameters and CBC are valuable to assessment for thrombosis and chemotherapy even for disease prognosis.

  18. Changes in skeletal muscle mass during palliative chemotherapy in patients with advanced lung cancer.

    Science.gov (United States)

    Stene, Guro B; Helbostad, Jorunn L; Amundsen, Tore; Sørhaug, Sveinung; Hjelde, Harald; Kaasa, Stein; Grønberg, Bjørn H

    2015-03-01

    Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. In total 35 patients, 48% women, mean age 67 years (range 56-86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% -7.3--1.9; pmuscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p=0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p=0.073). Stage of disease (p=0.003), treatment regimen (p=0.023), response to chemotherapy (p=0.007) and SMCA change (p=0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.

  19. Breast cancer patients on adjuvant chemotherapy report a wide range of problems not identified by health-care staff

    NARCIS (Netherlands)

    Groenvold, Mogens; Fayers, Peter M.; Petersen, Morten Aagard; Sprangers, Mirjam A. G.; Aaronson, Neil K.; Mouridsen, Henning T.

    2007-01-01

    BACKGROUND: Adjuvant chemotherapy for primary breast cancer is associated with significant side effects. The aims of this study were (1) to compare health-related quality of life (HRQL) in patients undergoing adjuvant chemotherapy to patients not on chemotherapy and (2) to compare these results

  20. [Role of induction chemotherapy in head and neck cancer: Cons].

    Science.gov (United States)

    Huguet, F; Schick, U; Pointreau, Y

    2017-10-01

    The treatment of locally advanced head and neck squamous cell carcinoma is based on concomitant chemoradiotherapy. A sequential treatment combining induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), followed by (chemo)radiotherapy is frequently used as part of laryngeal preservation strategies. Apart from this particular situation, the benefit in terms of survival of induction chemotherapy has been much discussed in recent years. In five recent randomized trials, chemoradiotherapy was compared with TPF induction chemotherapy followed by chemoradiotherapy. Of these five trials, four concluded that these treatments were similar. A single trial reports a benefit for induction chemotherapy but its methodology is highly debatable. After TPF chemotherapy, chemoradiotherapy is less well tolerated. In patients with significant lymph node invasion (N2b-c-N3), induction chemotherapy reduces the occurrence of distant metastasis. The HPV status should not influence the therapeutic decision. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  1. Dynamic contrast-enhanced MRI for monitoring response to neoadjuvant chemotherapy in breast cancer

    NARCIS (Netherlands)

    Loo, C.E.

    2016-01-01

    The general aim of this thesis is to investigate the role of dynamic contrast-enhanced MRI in monitoring response of breast cancer during neoadjuvant chemotherapy. The role of MRI with respect to achieving personalized breast cancer treatment by improving response monitoring is examined. Our

  2. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S; Bontenbal, M; Beex, LVAM; Wagstaff, J; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; van Tinteren, H; Peterse, HL; TenVergert, EM; de Vries, EGE

    2003-01-01

    BACKGROUND: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes. METHODS: Patients younger than 56 years of age who had undergone surgery for breast cancer

  3. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  4. Potential nanotechnologies and molecular targets in the quest for efficient chemotherapy in ovarian cancer.

    Science.gov (United States)

    Rhoda, Khadija; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2015-04-01

    Ovarian cancer, considered one of the most fatal gynecological cancers, goes largely undiagnosed until metastasis presents itself, usually once the patient is in the final stages and thus, too late for worthwhile therapy. Targeting this elusive disease in its early stages would improve the outcome for most patients, while the information generated thereof would increase the possibility of preventative mechanisms of therapy. This review discusses various molecular targets as possible moieties to be incorporated in a holistic drug delivery system or the more aptly termed 'theranostic' system. These molecular targets can be used for targeting, visualizing, diagnosing, and ultimately, treating ovarian cancer in its entirety. Currently implemented nanoframeworks, such as nanomicelles and nanoliposomes, are described and the effectiveness of nanostructures in tumor targeting, treatment functions, and overcoming the drug resistance challenge is discussed. Novel nanotechnology strategies such as the development of nanoframeworks decorated with targeted ligands of a molecular nature may provide an efficient chemotherapy, especially when instituted in combination with imaging, diagnostic, and ultimately, therapeutic moieties. An imperative aspect of utilizing nanotechnology in the treatment of ovarian cancer is the flexibility of the drug delivery system and its ability to overcome standard obstacles such as: i) successfully treating the desired cells through direct targeting; ii) reducing toxicity levels of treatment by achieving direct targeting; and iii) delivery of targeted therapy using an efficient vehicle that is exceptionally degradable in response to a particular stimulus. The targeting of ovarian cancer in its early stages using imaging and diagnostic nanotechnology is an area that can be improved upon by combining therapeutic moieties with molecular biomarkers. The nanotechnology and molecular markers mentioned in this review have generally been used for either

  5. Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer.

    Science.gov (United States)

    Kelemen, Linda E; Warren, Graham W; Koziak, Jennifer M; Köbel, Martin; Steed, Helen

    2016-01-01

    Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Chemotherapy-induced Fatigue among Jordanian Cancer Patients: What are the Contributing Factors?

    Directory of Open Access Journals (Sweden)

    Kholoud Abu Obead

    2014-03-01

    Full Text Available Background: The purposes of this study were to examine the impact of chemotherapy treatment on Jordanian cancer patients’ fatigue and to correlate their fatigue with selected sociodemographic variables at the beginning of treatment and after four weeks of treatment. Methods: This was a single group quasi-experimental correlational design study that enrolled 43 patients diagnosed with cancer who required chemotherapy treatment. Fatigue was measured according to the Piper Fatigue Scale (PFS before starting chemotherapy treatment and after four weeks of receiving the first dose of chemotherapy. Data were collected over a period of four weeks and analyzed with descriptive statistics, the paired-sample t-test, and Pearson product-moment correlation. Results: The study included 17 (39.5% males and 26 (60.5% females with a mean age of 45.98 years. Most (n=17 were diagnosed with breast cancer. Obesity was present in about 64.4% of patients. The majority (46% received an anthracycline-based regimen. There were statistically significant differences between respondents’ total mean scores of fatigue pre-treatment and four weeks following chemotherapy treatment (t= -2.31, df=42, P<0.05. In addition, significant differences were found in the scores for behavioral, affective, sensory, and cognitive dimensions subscales (t= -2.24, -2.19, - 2.4, -2.4, df=42, P<0.05 between pre-treatment and four weeks after receiving the first dose of chemotherapy treatment. We observed a significant negative relationship between fatigue scores and hemoglobin levels (r= -0.04, P<0.01. Conclusion: Cancer-related fatigue is common among cancer patients who received chemotherapy and result in substantial adverse physical, behavioral, cognitive and affective consequences for patient. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.

  7. Expression of the breast cancer resistance protein in breast cancer

    NARCIS (Netherlands)

    Faneyte, Ian F.; Kristel, Petra M. P.; Maliepaard, Marc; Scheffer, George L.; Scheper, Rik J.; Schellens, Jan H. M.; van de Vijver, Marc J.

    2002-01-01

    PURPOSE: The breast cancer resistance protein (BCRP) is involved in in vitro multidrug resistance and was first identified in the breast cancer cell line MCF7/AdrVp. The aim of this study was to investigate the role of BCRP in resistance of breast cancer to anthracycline treatment. EXPERIMENTAL

  8. Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype

    Science.gov (United States)

    2014-07-01

    research, and provides networking, clinical rotations (inpatient and outpatient), mentorship, and didactic seminars with experienced cancer researchers...treatment for men with castration-resistant prostate cancer. In: Govindan R, ed 2012 ASCO Educational Book . Alexandria, VA: American Society of...Eur Urol 2013, epub ahead of press Sept 10, 2013. Chapters in books : 1. Armstrong AJ, Carducci MA. Chemotherapy for advanced prostate cancer. In

  9. Induction chemotherapy: to downgrade aggressive cancers to improve curability by surgery and/or radiotherapy.

    Science.gov (United States)

    Stephens, F O

    2001-11-01

    Induction chemotherapy can be effective in reducing locally advanced or aggressive cancers to improve their prospects of cure by planned follow-up surgery and/or radiotherapy. Systemic (intravenous) delivery is the simplest and most readily available method of administering induction chemotherapy. In some situations, a greater chemotherapy impact can be achieved by delivering a more concentrated dose of effective anti-cancer agents into the arterial blood supply of the cancer. Intra-arterial (i.a.) chemotherapy may or may not be advantageous. To achieve an advantage, the tumour must be fully contained in tissue supplied by one or more arteries that can be effectively cannulated and infused. The cancer must also be one known to respond better to concentrated chemotherapy and the agents used must be effective in the state in which they are delivered. The advantages must outweigh the likely increased risks of regional toxicity and experienced personnel and appropriate specialized equipment must be available to reduce any risk of mistakes made by the more exacting techniques of delivery. In general, systemic chemotherapy is most appropriate in treating tumours without a single artery of supply; when certain agents that are inactive until modified in body tissues (such as cyclophosphamide or DTIC) are to be used; when satisfactory responses can be achieved safely and more easily by systemic delivery; when technical skills and facilities for regional delivery are not available; or when the patient's general health, poor co-operation or long-term prognosis precludes the additional complexity of regional delivery. Intra-arterial infusion may have advantages in treating some locally advanced malignancies in the head and neck, a limb, some invasive stomach cancers and some breast cancers. Primary and some metastatic liver cancers, some pelvic cancers and possibly pancreatic malignancies may also respond well to initial direct chemotherapy infusion and are the subject of

  10. Women prefer adjuvant endocrine therapy to chemotherapy for breast cancer treatment.

    Science.gov (United States)

    Niikura, Naoki; Kimura, Morihiko; Iwamoto, Takayuki; Hayashi, Naoki; Shintoku, Junichi; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2013-01-01

    We attempted to determine the preferences of women regarding the benefits they considered necessary to make adjuvant therapy worthwhile, and to compare preferences for adjuvant endocrine therapy, chemotherapy, and trastuzumab therapy. We also investigated the effect of information about cost on women's treatment preferences. Consecutive women who had a medical examination at the Breast Clinic, Ota General Hospital, were included in our study. We collected a questionnaire from a total of 365 women; 297 completed responses were included in the study. Among 297 women, 105 had breast cancer that had been treated and 192 did not have breast cancer; 38% of women judged that a 5% or less gain in the probability of survival was sufficient to make endocrine therapy worthwhile; 28% of participants judged that chemotherapy was worthwhile; 24% of participants judged that trastuzumab therapy was worthwhile. Women indicated that they were more likely to receive adjuvant endocrine therapy than chemotherapy or trastuzumab therapy, for the same gains in the probability of survival. Cost information about treatments did not affect women's treatment preferences. Younger women tended to judge improvements in survival sufficient to make adjuvant endocrine and chemotherapy worthwhile, as compared to older women. The comparisons were statistically significant in the 10 and 20% categories for endocrine therapy and chemotherapy. Women prefer endocrine therapy to chemotherapy or trastuzumab therapy, given the same projected treatment benefits. Younger women prefer both chemotherapy and endocrine therapy as compared with older woman.

  11. Dietary habits changes and quality of life in patients undergoing chemotherapy for epithelial ovarian cancer.

    Science.gov (United States)

    Mardas, Marcin; Jamka, Małgorzata; Mądry, Radosław; Walkowiak, Jarosław; Krótkopad, Marietta; Stelmach-Mardas, Marta

    2015-04-01

    The aim of this study was to evaluate dietary habit changes in patients undergoing chemotherapy for epithelial ovarian cancer. Sixty one patients undergoing chemotherapy for epithelial ovarian cancer were enrolled to the study and 44 completed. The dietary intake was evaluated by 7-day food records, and the changes in dietary intake and food-preparing methods were estimated based on a 101-item semiquantitative food frequency questionnaire. Nutritional status was checked with the use of body weight and height, waist and hip circumferences, skinfolds and subjective global assessment tool. Quality of life was measured with the use of EORTC QLQ-C30 and EORTC QLQ-OV28. Despite high average body mass index (BMI) (26.7-28.0 kg/m(2)), malnutrition risk was observed in 43.7 and 10.7 % of patients receiving first-line and subsequent-line chemotherapy, respectively (p life did not differ between the studied groups. A lot of dietary habits changes were observed. Women undergoing subsequent-line chemotherapy consumed more frequently rye bread, pasta, buttermilk, vegetable, fruit, oils, nuts, and juices. Women undergoing first-line chemotherapy consumed more milk, cottage cheese, cream, eggs, fish and seafood, meat offal, salty snacks, and jam. Additionally, women undergoing subsequent-line chemotherapy more often applied cooking in water (p habits in a pro healthy direction, and these changes are more expressed in patients undergoing subsequent-line chemotherapy.

  12. Prayer-for-health and complementary alternative medicine use among Malaysian breast cancer patients during chemotherapy

    OpenAIRE

    Chui, Ping Lei; Abdullah, Khatijah Lim; Wong, Li Ping; Taib, Nur Aishah

    2014-01-01

    Background The inclusion of prayer-for-health (PFH) in the definition of complementary alternative medicine (CAM) has resulted in higher levels of CAM use. The objective of this study was to assess PFH and CAM use among breast cancer patients undergoing chemotherapy. Methods A cross-sectional study was performed at two chemotherapy providers. Patients were questioned about use of three categories of CAM, mind-body practices (MBPs), natural products (NPs) and traditional medicine (TM). PFH was...

  13. Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer

    Directory of Open Access Journals (Sweden)

    Palesh O

    2012-12-01

    Full Text Available Oxana Palesh,1 Luke Peppone,2 Pasquale F Innominato,3–5 Michelle Janelsins,2 Monica Jeong,1 Lisa Sprod,7 Josee Savard,6 Max Rotatori,1 Shelli Kesler,1 Melinda Telli,1 Karen Mustian21Stanford University School of Medicine, Stanford, CA, USA; 2University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 3INSERM, UMRS 776, Biological Rhythms and Cancers, Villejuif, France; 4Faculty of Medicine, Universite Paris Sud, le Kremlin-Bicêtre, France; 5APHP, Chronotherapy Unit, Department of Oncology, Paul Brousse Hospital, Villejuif, France; 6Laval University, Quebec, Canada; 7University of North Carolina, Wilmington, NC, USAAbstract: Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients

  14. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

    Science.gov (United States)

    Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

    2016-01-01

    Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer.

    Science.gov (United States)

    Torgeson, Anna; Lloyd, Shane; Boothe, Dustin; Tao, Randa; Whisenant, Jonathan; Garrido-Laguna, Ignacio; Cannon, George M

    2017-10-01

    The role of chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) is uncertain after multiple randomized clinical trials have yielded mixed results. The authors used the National Cancer Data Base (NCDB) to determine whether CRT yields a survival benefit compared with chemotherapy alone (CT). Patients with nonmetastatic LAPC diagnosed during 2004 through 2014 were identified in the NCDB. Patients who received CT were compared with those who received CRT using chi-square analysis. Univariate and multivariate Cox regression analyses were used to compare demographic, clinical, and treatment characteristics that were predictive of survival. Propensity score matching and shared frailty analysis were done. Subgroup analyses were undertaken to examine patients who underwent pancreatectomy and cohorts of patients who received different CT or CRT regimens. In total, 8689 patients with LAPC were identified. CRT was associated with improved survival (median survival [MS], 13.5 months) compared with CT (MS, 10.6 months) on multivariate analysis (hazard ratio [HR], 0.80; P chemotherapy before CRT (HR, 0.67; P chemotherapy (HR, 0.72; P chemotherapy had superior MS and pancreatectomy rates (MS, 17.5 months; HR, 0.70; P improved survival (MS, 22 vs 10.6 months; HR, 0.39; P chemotherapy before CRT improved survival compared with CT alone in patients with LAPC. Continued analysis of CRT in properly selected patients after maximized systemic therapy is needed. Cancer 2017;123:3816-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. The Impact of Sucking Bits of Ice Containing Mint on Nausea and Vomiting During Chemotherapy in Patients with Breast Cancer

    OpenAIRE

    Mohammad Haddadi; Javad Ganjloo; Hamid Reza Hashemifard; Yasser Tabarraie

    2016-01-01

    Background: Cancer remains as one of the most challenging diseases to be tackled in today’s world. Improving treatment methods can contribute to fighting cancer better than before. Breast cancer is one of the most common and significant diseases which problematizes a large number of women. Various methods are used in order to cure breast cancer, including surgery, radiotherapy and chemotherapy. Chemotherapy is one of the oldest and most common treatments for cancer. Nausea and vomiting are th...

  17. A Case Report of Metastatic Breast Cancer Treated with Korean Medicine Therapy as a Substitute for Chemotherapy

    Directory of Open Access Journals (Sweden)

    Dong-hyun Lee

    2017-01-01

    Full Text Available The purpose of this case report is to show the potential benefit of Korean medicine therapy for treating multiple metastatic breast cancer. A 45-year-old Korean woman was diagnosed with right breast invasive ductal carcinoma in August 2012 but did not receive any treatment until October 2015 when she was diagnosed with stage 4 right breast cancer with multiple liver, bone, mesentery, retroperitoneum, and axillary lymph node metastases. After chemo-port insertion, she was treated with palliative chemotherapy and the first line of trastuzumab and paclitaxel, and the port was removed due to port infection. To treat sepsis, vancomycin and tazoperan were administered, before the third line of trastuzumab and paclitaxel was carried out. However, the patient gave up chemotherapy due to vancomycin-resistant enterococci and general weakness. Later, she received Korean medicine therapy with wild ginseng pharmacopuncture, distilled Soramdan S, Hae, and Jeobgoldan for 8 months, which led to a significant decrease of the multiple metastases. The patient was able to start walking again with the help of a walking stick. However, a new metastatic lesion was found on the right adrenal gland. This case suggests that the combination of chemotherapy and Korean medicine therapy may be valuable. Further research is indicated.

  18. GLI1-mediated regulation of side population is responsible for drug resistance in gastric cancer

    Science.gov (United States)

    Yu, Beiqin; Gu, Dongsheng; Zhang, Xiaoli; Li, Jianfang; Liu, Bingya; Xie, Jingwu

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for cancer relapse following chemotherapy will help design new ways to treat gastric cancer. In this study, we revealed that the residual cancer cells following treatment with chemotherapeutic reagent cisplatin have elevated expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog signaling activation. We showed that GLI1 knockdown sensitized gastric cancer cells to CDDP whereas ectopic GLI1 expression decreased the sensitivity. Further analyses indicate elevated GLI1 expression is associated with an increase in tumor sphere formation, side population and cell surface markers for putative cancer stem cells. We have evidence to support that GLI1 is critical for maintenance of putative cancer stem cells through direct regulation of ABCG2. In fact, GLI1 protein was shown to be associated with the promoter fragment of ABCG2 through a Gli-binding consensus site in gastric cancer cells. Disruption of ABCG2 function, through ectopic expression of an ABCG2 dominant negative construct or a specific ABCG2 inhibitor, increased drug sensitivity of cancer cells both in culture and in mice. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high ABCG2 expression was associated with poor survival in the gastric cancer patients who underwent chemotherapy. Taken together, we have identified a molecular mechanism by which gastric cancer cells gain chemotherapy resistance. PMID:28404967

  19. Resistance to antitumor chemotherapy due to bounded-noise-induced transitions.

    Science.gov (United States)

    d'Onofrio, Alberto; Gandolfi, Alberto

    2010-12-01

    Tumor angiogenesis is a landmark of solid tumor development, but it is also directly relevant to chemotherapy. Indeed, the density and quality of neovessels may influence the effectiveness of therapies based on blood-born agents. In this paper, first we define a deterministic model of antiproliferative chemotherapy in which the drug efficacy is a unimodal function of vessel density, and then we show that under constant continuous infusion therapy the tumor-vessel system may be multistable. However, the actual drug concentration profiles are affected by bounded even if possibly large fluctuations. Through numerical simulations, we show that the tumor volume may undergo transitions to the higher equilibrium value induced by the bounded noise. In case of periodically delivered boli-based chemotherapy, we model the fluctuations due to time variability of both the drug clearance rate and the distribution volume, as well as those due to irregularities in drug delivery. We observed noise-induced transitions also in case of periodic delivering. By applying a time dense scheduling with constant average delivered drug (metronomic scheduling), we observed an easier suppression of the transitions. Finally, we propose to interpret the above phenomena as an unexpected non-genetic kind of resistance to chemotherapy.

  20. Castration-resistant prostate cancer: AUA Guideline.

    Science.gov (United States)

    Cookson, Michael S; Roth, Bruce J; Dahm, Philipp; Engstrom, Christine; Freedland, Stephen J; Hussain, Maha; Lin, Daniel W; Lowrance, William T; Murad, Mohammad Hassan; Oh, William K; Penson, David F; Kibel, Adam S

    2013-08-01

    This Guideline is intended to provide a rational basis for the management of patients with castration-resistant prostate cancer based on currently available published data. A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with keywords relating to the relevant concepts of prostate cancer and castration resistance. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 303 articles published from 1996 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. Guideline statements were created to inform clinicians on the appropriate use of observation, androgen-deprivation and antiandrogen therapy, androgen synthesis inhibitors, immunotherapy, radionuclide therapy, systemic chemotherapy, palliative care and bone health. These were based on six index patients developed to represent the most common scenarios encountered in clinical practice. As a direct result of the significant increase in FDA-approved therapeutic agents for use in patients with metastatic CRPC, clinicians are challenged with a multitude of treatment options and potential sequencing of these agents that, consequently, make clinical decision-making more complex. Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. In all cases, patients' preferences and personal goals should be considered when choosing management strategies. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. DNA damage in peripheral blood lymphocytes in patients during combined chemotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Suarez, Patricia [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Ostrosky-Wegman, Patricia [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Gallegos-Hernandez, Francisco [Department of Clinical Oncology, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City (Mexico); Penarroja-Flores, Rubicelia; Toledo-Garcia, Jorge [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Bravo, Jose Luis [Atmospheric Sciences Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Rojas del Castillo, Emilio [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Benitez-Bribiesca, Luis [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico)], E-mail: luisbenbri@mexis.com

    2008-04-02

    Combined chemotherapy is used for the treatment of a number of malignancies such as breast cancer. The target of these antineoplastic agents is nuclear DNA, although it is not restricted to malignant cells. The aim of the present study was to assess DNA damage in peripheral blood lymphocytes (PBLs) of breast cancer patients subjected to combined adjuvant chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide, FEC), using a modified comet assay to detect DNA single-strand breaks (SSB) and double-strand breaks (DSB). Forty-one female patients with advanced breast cancer before and after chemotherapy and 60 healthy females participated in the study. Alkaline and neutral comet assays were performed in PBLs according to a standard protocol, and DNA tail moment was measured by a computer-based image analysis system. Breast cancer patients before treatment had higher increased background levels of SSB and DSB as compared to healthy women. During treatment, a significant increase in DNA damage was observed after the 2nd cycle, which persisted until the end of treatment. Eighty days after the end of treatment the percentage of PBLs with SSB and DSB remained elevated, but the magnitude of DNA damage (tail moment) returned to baseline levels. There was no correlation between PBL DNA damage and response to chemotherapy. DNA-SSB and DSB in PBLs are present in cancer patients before treatment and increase significantly after combined chemotherapy. No correlation with response to adjuvant chemotherapy was found. Biomonitoring DNA damage in PBLs of cancer patients could help prevent secondary effects and the potential risks of developing secondary cancers.

  2. Estimation of the cost of treatment by chemotherapy for early breast cancer in Morocco

    Directory of Open Access Journals (Sweden)

    Boutayeb Saber

    2010-09-01

    Full Text Available Abstract Background Breast cancer is the first cancer in women both in incidence and mortality. The treatment of breast cancer benefited from the progress of chemotherapy and targeted therapies, but there was a parallel increase in treatment costs. Despite a relatively high incidence of many sites of cancer, so far, there is no national register for this disease in Morocco. The main goal of this paper is to estimate the total cost of chemotherapy in the early stages of breast cancer due to its frequency and the chances of patients being cured. This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of antimitotics and trastuzumab in Morocco. Method We start by evaluating the individual cost according to the therapeutic sub-groups, namely: 1. Patients needing chemotherapy with only anthracycline-based therapy. 2. Patients needing chemotherapy with both anthracycline and taxane but without trastuzumab. 3. Patients needing trastuzumab in addition to chemotherapy. For each sub-group, the protocol of treatment is described, and the individual costs per unit, and for the whole cycle, are evaluated. Then we estimate the number of women suffering from breast cancer on the basis of two data bases available in Morocco. Finally, we calculate the total annual cost of treatment of breast cancer in Morocco. Results The total cost of breast cancer in Morocco is given in Moroccan dirhams (MAD, the US dollar at the current exchange rate (MAD 10 = USD 1.30 and in international dollars or purchasing power parity (MAD 10 = PPP 1.95. The cost of a therapy with trastuzumab is 8.4 times the cost of a sequential chemotherapy combining anthracycline and taxane, and nearly 60 times the cost of chemotherapy based on anthracycline alone. Globally, between USD 13.3 million and USD 28.6 million need to be devoted every year by the Moroccan health authorities to treat

  3. FDG uptake after intraarterial chemotherapy in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doebert, N. [Univ. Hospital Frankfurt am Main (Germany). Dept. of Nuclear Medicine; Gemeinschaftspraxis Nuklearmedizin, Darmstadt (Germany); Kovacs, A.F. [Univ. Hospital Frankfurt am Main (Germany). Dept. of Maxillofacial Plastic Surgery; Menzel, C.; Kranert, W.T.; Gruenwald, F. [Univ. Hospital Frankfurt am Main (Germany). Dept. of Nuclear Medicine; Engels, K. [Senckenberg Dept. of Pathology, Univ. Hospital Frankfurt am Main (Germany)

    2006-07-01

    Aim: the intraarterial chemotherapy (i.a.CHT) using high dose cisplatin combined with systemic neutralization in patients with head and neck cancer (HNSCC) is used to reduce the tumor volume preoperatively. Aim of the study is the evaluation of the influence of i.a.CHT on the metabolism of fluor-18-deoxyglucose (FDG) in the primary and lymph nodes (LN). The value of FDG positron emission tomography (PET) preoperative and as follow-up method otter i.a.CHT is examined. Patients, methods: altogether 16 patients with HNSCC underwent two preoperative FDG PET examinations: the baseline examination one week before and the follow-up three weeks after i.a.CHT. The SUVmax values of the primary and the IN and LN metastases were evaluated and compared with each other and the histopathology. Results: the SUVmax value of the primary decreased after i.a.CHT significantly from a median (25{sup th} percentile/ 75{sup th} percentile) of 6.4 (4.1/ 7.8) to 3.6 (2.4/ 6.7) (p = 0.01). In 11 out of 16 patients cervical LN metastases were detected. The cervical LN metastases showed a decrease of the SUVmax value from 3.6 (2.3/ 4.8) in the pretreatment examination to 2.3 (1.7/ 3.6) after i.a.CHT (p = 0,008). Only in one patient with LN metastases the SUVmax of the nodes increased. The histopathologically measured size of the LN metastases ranged from 2 to 30 mm. Non malignant LN did not reveal a significant SUVmax decrease after i.a.CHT (p = 0.13). Conclusions: as expected, primaries of HNSCC showed a significant reduction of SUV after i.a.CHT. Compared to the primary the SUVmax decrease in LN metastases was less, but also significant. Since cytotoxic levels of cisplatin do not occur systemic, postinflammatory reactions of the LN or a lymphatic drainage of the chemotherapeutic drug into the LN could be an explanation. PET for staging of HNSCC must thus be performed prior to i.a.CHT. (orig.)

  4. Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.

    Science.gov (United States)

    Farge, Thomas; Saland, Estelle; de Toni, Fabienne; Aroua, Nesrine; Hosseini, Mohsen; Perry, Robin; Bosc, Claudie; Sugita, Mayumi; Stuani, Lucille; Fraisse, Marine; Scotland, Sarah; Larrue, Clément; Boutzen, Héléna; Féliu, Virginie; Nicolau-Travers, Marie-Laure; Cassant-Sourdy, Stéphanie; Broin, Nicolas; David, Marion; Serhan, Nizar; Sarry, Audrey; Tavitian, Suzanne; Kaoma, Tony; Vallar, Laurent; Iacovoni, Jason; Linares, Laetitia K; Montersino, Camille; Castellano, Rémy; Griessinger, Emmanuel; Collette, Yves; Duchamp, Olivier; Barreira, Yara; Hirsch, Pierre; Palama, Tony; Gales, Lara; Delhommeau, François; Garmy-Susini, Barbara H; Portais, Jean-Charles; Vergez, François; Selak, Mary; Danet-Desnoyers, Gwenn; Carroll, Martin; Récher, Christian; Sarry, Jean-Emmanuel

    2017-07-01

    Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSC). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly, AraC-resistant preexisting and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated CD36 expression, and a high OXPHOS gene signature predictive for treatment response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML cell lines were chemoresistant in vivo. Targeting mitochondrial protein synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together, this study demonstrates that essential mitochondrial functions contribute to AraC resistance in AML and are a robust hallmark of AraC sensitivity and a promising therapeutic avenue to treat AML residual disease.Significance: AraC-resistant AML cells exhibit metabolic features and gene signatures consistent with a high OXPHOS status. In these cells, targeting mitochondrial metabolism through the CD36-FAO-OXPHOS axis induces an energetic shift toward low OXPHOS and strongly enhanced antileukemic effects of AraC, offering a promising avenue to design new therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716-35. ©2017 AACR.See related commentary by Schimmer, p. 670This article is highlighted in the In This Issue feature, p. 653. ©2017 American Association for Cancer Research.

  5. Multidisciplinary Optimization of Oral Chemotherapy Delivery at the University of Wisconsin Carbone Cancer Center.

    Science.gov (United States)

    Mulkerin, Daniel L; Bergsbaken, Jason J; Fischer, Jessica A; Mulkerin, Mary J; Bohler, Aaron M; Mably, Mary S

    2016-10-01

    Use of oral chemotherapy is expanding and offers advantages while posing unique safety challenges. ASCO and the Oncology Nursing Society jointly published safety standards for administering chemotherapy that offer a framework for improving oral chemotherapy practice at the University of Wisconsin Carbone Cancer Center. With the goal of improving safety, quality, and uniformity within our oral chemotherapy practice, we conducted a gap analysis comparing our practice against ASCO/Oncology Nursing Society guidelines. Areas for improvement were addressed by multidisciplinary workgroups that focused on education, workflows, and information technology. Recommendations and process changes included defining chemotherapy, standardizing patient and caregiver education, mandating the use of comprehensive electronic order sets, and standardizing documentation for dose modification. Revised processes allow pharmacists to review all orders for oral chemotherapy, and they support monitoring adherence and toxicity by using a library of scripted materials. Between August 2015 and January 2016, revised processes were implemented across the University of Wisconsin Carbone Cancer Center clinics. The following are key performance indicators: 92.5% of oral chemotherapy orders (n = 1,216) were initiated within comprehensive electronic order sets (N = 1,315), 89.2% compliance with informed consent was achieved, 14.7% of orders (n = 193) required an average of 4.4 minutes review time by the pharmacist, and 100% compliance with first-cycle monitoring of adherence and toxicity was achieved. We closed significant gaps between institutional practice and published standards for our oral chemotherapy practice and experienced steady improvement and sustainable performance in key metrics. We created an electronic definition of oral chemotherapies that allowed us to leverage our electronic health records. We believe our tools are broadly applicable.

  6. Narrowing Racial Gaps in Breast Cancer Chemotherapy Initiation: The Role of the Patient-Provider Relationship

    Science.gov (United States)

    Sheppard, Vanessa B.; Isaacs, Claudine; Luta, George; Willey, Shawna C.; Boisvert, Marc; Harper, Felicity W. K.; Smith, Karen; Horton, Sara; Liu, Minetta C.; Jennings, Yvonne; Hirpa, Fikru; Snead, Felicia; Mandelblatt, Jeanne S.

    2013-01-01

    Purpose Chemotherapy improves breast cancer survival but is underused more often in black than in white women. We examined associations between patient-physician relationships and chemotherapy initiation and timeliness of initiation among black and white patients. Methods Women with primary invasive, non-metastatic breast cancer were recruited via hospitals (in Washington, DC and Detroit) and community outreach between July 2006 and April 2011. Data were collected via telephone interviews and medical records. Logistic regression models evaluated associations between chemotherapy initiation and independent variables. Since there were race interactions, analyses were race-stratified. Factors associated with time from surgery to chemotherapy initiation and delay of ≥ 90 days were evaluated with linear and logistic regressions, respectively. Results Among eligible women, 82.8% were interviewed and 359 (90.9%)of those had complete data. The odds of initiating chemotherapy were 3.26 times (95% CI: 1.51, 7.06) higher among black women reporting greater communication with physicians (vs. lesser), after considering covariates. In contrast, the odds of starting chemotherapy were lower for white women reporting greater communication (vs. lesser) (adjusted OR .22, 95% CI: .07, .73). The opposing direction of associations was also seen among the sub-set of black and white women with definitive clinical indications for chemotherapy. Among those initiating treatment, black women had longer mean time to the start of chemotherapy than whites (71.8 days vs. 55.0 days, p= .005), but race was not significant after considering trust in oncologists, where initiation time decreased as trust increased, controlling for covariates. Black women were also more likely to delay ≥ 90 days than whites (27% vs. 8.3%; p=.024), but this was not significant after considering religiosity. Conclusion The patient-physician dyad and sociocultural factors may represent leverage points to improve

  7. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

    Directory of Open Access Journals (Sweden)

    Valerie A. Allen

    2016-01-01

    Full Text Available Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI. Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  8. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy.

    Science.gov (United States)

    Allen, Valerie A; Manahan, Kelly J; Geisler, John P

    2016-01-01

    Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient's diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  9. Effect of a Multimodal High Intensity Exercise Intervention in Cancer Patients Undergoing Chemotherapy

    DEFF Research Database (Denmark)

    Adamsen, Lis; Quist, Morten; Andersen, Christina

    2009-01-01

    Abstract: Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for adv...... chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life.......Abstract: Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment...... Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo2max). Statistical methods: The general linear...

  10. Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

    Science.gov (United States)

    Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

    2016-06-01

    Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them i