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Sample records for cancer patients resistant

  1. Antibiotic resistance in cancer patients.

    Science.gov (United States)

    Gudiol, Carlota; Carratalà, Jordi

    2014-08-01

    Bacterial infection is one of the most frequent complications in cancer patients and hematopoietic stem cell transplant recipients. In recent years, the emergence of antimicrobial resistance has become a significant problem worldwide, and cancer patients are among those affected. Treatment of infections due to multidrug-resistant (MDR) bacteria represents a clinical challenge, especially in the case of Gram-negative bacilli, since the therapeutic options are often very limited. As the antibiotics active against MDR bacteria present several disadvantages (limited clinical experience, higher incidence of adverse effects, and less knowledge of the pharmacokinetics of the drug), a thorough acquaintance with the main characteristics of these drugs is mandatory in order to provide safe treatment to cancer patients with MDR bacterial infections. Nevertheless, the implementation of antibiotic stewardship programs and infection control measures is the cornerstone for controlling the development and spread of these MDR pathogens.

  2. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance.

    Science.gov (United States)

    Montassier, E; Batard, E; Gastinne, T; Potel, G; de La Cochetière, M F

    2013-07-01

    Bacteremia remains a major cause of life-threatening complication in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture have been reported in cancer patients over the past years. The aim of our systematic review was to inventory the recent trends in epidemiology and antibiotic resistance of microorganisms causing bacteremia in cancer patients. Data for this review was identified by searches of Medline, Scopus and Cochrane Library for indexed articles and abstracts published in English since 2008. The principal search terms were: "antimicrobial resistance", "bacteremia", "bacterial epidemiology", "bloodstream infection", "cancer patients", "carbapenem resistance", "Escherichia coli resistance", "extended-spectrum β-lactamase producing E. coli", "febrile neutropenia", "fluoroquinolone resistance", "neutropenic cancer patient", "vancomycin-resistant Enterococcus", and "multidrug resistance". Boolean operators (NOT, AND, OR) were also used in succession to narrow and widen the search. Altogether, 27 articles were selected to be analyzed in the review. We found that Gram-negative bacteria were the most frequent pathogen isolated, particularly in studies with minimal use of antibiotic prophylaxis. Another important trend is the extensive emergence of antimicrobial-resistant strains associated with increased risk of morbidity, mortality and cost. This increasing incidence of antibiotic resistance has been reported in Gram-negative bacteria as well as in Gram-positive bacteria. This exhaustive review, reporting the recent findings in epidemiology and antibiotic resistance of bacteremia in cancer patients, highlights the necessity of local continuous surveillance of bacteremia and stringent enforcement of antibiotic stewardship programs in cancer patients.

  3. Herceptin resistance database for understanding mechanism of resistance in breast cancer patients.

    Science.gov (United States)

    Ahmad, Sahil; Gupta, Sudheer; Kumar, Rahul; Varshney, Grish C; Raghava, Gajendra P S

    2014-03-27

    Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains information about 2500 assays performed against various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin with or without supplementary drugs. In order to understand Herceptin resistance at genetic level, we integrated genomic data of BCCs that include expression, mutations and copy number variations in different cell lines. HerceptinR will play a vital role in i) designing biomarkers to identify patients eligible for Herceptin treatment and ii) identification of appropriate supplementary drug for a particular patient. HerceptinR is available at http://crdd.osdd.net/raghava/herceptinr/.

  4. Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Oudard, Stéphane; Kramer, Gero; Caffo, Orazio

    2015-01-01

    OBJECTIVE: To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients with mCRPC w...

  5. 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...

  6. BAY 1024767 blocks androgen receptor mutants found in castration-resistant prostate cancer patients.

    Science.gov (United States)

    Sugawara, Tatsuo; Lejeune, Pascale; Köhr, Silke; Neuhaus, Roland; Faus, Hortensia; Gelato, Kathy A; Busemann, Matthias; Cleve, Arwed; Lücking, Ulrich; von Nussbaum, Franz; Brands, Michael; Mumberg, Dominik; Jung, Klaus; Stephan, Carsten; Haendler, Bernard

    2016-02-01

    Androgen receptor (AR) mutations arise in patients developing resistance to hormone deprivation therapies. Here we describe BAY 1024767, a thiohydantoin derivative with strong antagonistic activity against nine AR variants with mutations located in the AR ligand-binding domain (LBD), and against wild-type AR. Antagonism was maintained, though reduced, at increased androgen levels. Anti-tumor efficacy was evidenced in vivo in the KuCaP-1 prostate cancer model which bears the W741C bicalutamide resistance mutation and in the syngeneic prostate cancer rat model Dunning R3327-G. The prevalence of six selected AR mutations was determined in plasma DNA originating from 100 resistant patients and found to be at least 12%. Altogether the results show BAY 1024767 to be a strong antagonist for several AR mutants linked to therapy resistance, which opens the door for next-generation compounds that can benefit patients based on their mutation profile.

  7. Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer

    Directory of Open Access Journals (Sweden)

    Leamon PC

    2013-09-01

    Full Text Available Christopher P Leamon,1 Chandra D Lovejoy,2 Binh Nguyen3 1Research and Development, 2Regulatory Affairs, 3Clinical Affairs, Endocyte Inc, West Lafayette, IN, USA Abstract: Ovarian cancer (OC has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and gemcitabine, but many patients eventually relapse upon treatment. Fortunately, there are currently a number of targeted therapies in development for these patients who have shown promising results in recent clinical trials. These treatments often target the vascular endothelial growth factor pathway (eg, bevacizumab and aflibercept, DNA repair mechanisms (eg, iniparib and olaparib, or they are directed against folate related pathways (eg, pemetrexed, farletuzumab, and vintafolide. As many targeted therapies are only effective in a subset of patients, there is an increasing need for the identification of response predictive biomarkers. Selecting the right patients through biomarker screening will help tailor therapy to patients and decrease superfluous treatment to those who are biomarker negative; this approach should lead to improved clinical results and decreased toxicities. In this review the current targeted therapies used for treating platinum-resistant OC are discussed. Furthermore, use of prognostic and response predictive biomarkers to define OC patient populations that may benefit from specific targeted therapies is also highlighted. Keywords: platinum-resistant ovarian cancer, targeted therapy, patient selection, folate receptor, VEGF, biomarkers

  8. The frequency and antimicrobial resistance patterns of nosocomial pathogens recovered from cancer patients and hospital environments

    Institute of Scientific and Technical Information of China (English)

    Aymen Mudawe Nurain; Naser Eldin Bilal; Mutasim Elhadi Ibrahim

    2015-01-01

    Objective: To determine the prevalence and antimicrobial resistance rates of nosocomial pathogens isolated from cancer patients and hospital environments. Methods: A descriptive cross-sectional study was conducted between December 2010 to May 2013 at Radiation and Isotopes Centre of Khartoum, Sudan. A total of 1 503 samples (505 clinical and 998 environmental) were examined. Isolates were identified, and their antimicrobial susceptibility was determined using standard laboratory procedures. Results: Out of 505 clinical samples, nosocomial pathogens were found as 48.1%. Among hospital environment samples, bacterial contaminants were detected in 29.7%of samples. The main microorganisms recovered from cancer patients were Proteus spp. (23.5%), Escherichia coli (22.2%), Pseudomonas aeruginosa (P. aeruginosa) (21.0%) and Staphylococcus aureus (20.2%). The most frequent isolates from hospital environ-ments were Bacillus spp. (50.0%), Staphylococcus aureus (14.2%) and P. aeruginosa (11.5%). The proportions of resistance among Gram-negative pathogens from cancer patients were high for ampicillin, cefotaxime, ceftazidime and ceftriaxone. Moderate resistance rates were recorded to ciprofloxacin, such as 51.0%for P. aeruginosa, 21.7%for Klebsiella pneumoniae and 55.5%for Escherichia coli. Except Klebsiella, there were no significant differences (P ? 0.05) of resistance rates between Gram-negative isolates from cancer patients to those from the hospital environments. The proportions of extended-spectrum b-lactamase producing isolates from cancer patients were not differ significantly (P=0.763) from those collected from the hospital environments (49.2%;91/185 vs. 47%;32/68). Conclusions: The prevalence of nosocomial infection among cancer patients was high (48.1%) with the increasing of antimicrobial resistance rates. Hospital environments are potential reservoirs for nosocomial infections, which calls for intervention program to reduce environmental transmission of pathogens.

  9. The frequency and antimicrobial resistance patterns of nosocomial pathogens recovered from cancer patients and hospital environments

    Institute of Scientific and Technical Information of China (English)

    Aymen; Mudawe; Nurain; Naser; Eldin; Bilal; Mutasim; Elhadi; Ibrahim

    2015-01-01

    Objective:To determine the prevalence and antimicrobial resistance rates of nosocomial pathogens isolated from cancer patients and hospital environments.Methods:A descriptive cross-sectional study was conducted between December 2010 to May 2013 at Radiation and Isotopes Centre of Khartoum,Sudan.A total of 1 503 samples(505 clinical and 998 environmental)were examined.Isolates were identified,and their antimicrobial susceptibility was determined using standard laboratory procedures.Results:Out of 505 clinical samples,nosocomial pathogens were found as 48.1%.Among hospital environment samples,bacterial contaminants were detected in 29.7%of samples.The main microorganisms recovered from cancer patients were Proteus spp.(23.5%),Escherichia coli(22.2%),Pseudomonas aeruginosa(P.aeruginosa)(21.0%)and Staphylococcus aureus(20.2%).The most frequent isolates from hospital environments were Bacillus spp.(50.0%),Staphylococcus aureus(14.2%)and P.aeruginosa(11.5%).The proportions of resistance among Gram-negative pathogens from cancer patients were high for ampicillin,cefotaxime,ceftazidime and ceftriaxone.Moderate resistance rates were recorded to ciprofloxacin,such as 51.0%for P.aeruginosa,21.7%for Klebsiella pneumoniae and 55.5%for Escherichia coli.Except Klebsiella,there were no significant differences(P0.05)of resistance rates between Gram-negative isolates from cancer patients to those from the hospital environments.The proportions of extended-spectrum b-lactamase producing isolates from cancer patients were not differ significantly(P=0.763)from those collected from the hospital environments(49.2%;91/185 vs.47%;32/68).Conclusions:The prevalence of nosocomial infection among cancer patients was high(48.1%)with the increasing of antimicrobial resistance rates.Hospital environments are potential reservoirs for nosocomial infections,which calls for intervention program to reduce environmental transmission of pathogens.

  10. Biomarkers for Taxane Sensitivity and Hormonal Resistance in Patients with Castration Resistant Prostate Cancer

    Science.gov (United States)

    2016-04-01

    RNA to perform qRT- PCR for splice variants and variant transcriptome. Results: As described in the annual report, the Rarecyte assay originally...modified by Antonarakis et al (1). This assay reliably isolated splice variant transcript as detected by QT- PCR from as low as 5 spiked LNCaP 95 cells...transfectant cells compared to controls (data not shown). 1b. Determine if CTC from abiraterone resistant prostate cancers contain splice variant

  11. 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...

  12. New drugs in the treatment of elderly patients with metastatic castration-resistance prostate cancer.

    Science.gov (United States)

    Genestreti, Giovenzio; Di Battista, Monica; Cavallo, Giovanna; Brandes, Alba A

    2016-08-03

    Treatment of prostate cancer is continually evolving and new therapies have become available. However, the management of elderly patients is challenging due to their age and comorbidities. Androgen deprivation therapy remains the mainstay treatment of hormonal-sensitive disease. Nevertheless, when disease becomes resistant to castration, docetaxel-based chemotherapy represents the standard rescue therapy irrespective of patient age. Recently, chemotherapeutic agents such as cabazitaxel and hormonal therapies such as abiraterone acetate and enzalutamide have been shown to improve survival in patients with progression of disease before or following docetaxel. This review focuses on the safety and efficacy results of these new drugs in elderly patients.

  13. Preliminary Study Results Of Multiple Drug Resistance In Patients With Advanced Types Of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    S Navruzov

    2010-04-01

    Full Text Available In the department of coloproctology of NORC MH RUz 17 patients with disseminated forms of colorectal cancer was made the study of oncogenes and complex treatment by 2 protocols using FOLFOX-4 regime and FOLFIRI regime. In second protocol there used 2 sessions of endolymphatical polychemotherapy FOLFOX-4 regime against EHF-hyperthermia. All patients were performed additional investigations directed to study the presence of multiple drug resistance in them where definition of р53, bcl-2 oncogene expression. In our observations we followed resistance to FOLFOX-4 scheme in 4 patients, and to FOLFIRI scheme in 2 cases. In our studies hyperexpression of oncoproteine  р53 was correlated with the effect of conducted therapy whereas hyperexpression of oncoproteine bcl-2 showed therapy resistance

  14. Study of insulin resistance and antioxidant vitamin status in prostate cancer patients

    Directory of Open Access Journals (Sweden)

    S. Prasanth Vardhan

    2014-04-01

    Full Text Available The incidence of prostate cancer is 5 per 100000 in southern and eastern Asia. Both genetic and environmental factors have been implicated in its etiology. The mitogenic and growth stimulatory effects of Insulin growth factor may be involved in prostate carcinogenesis. To evaluate serum insulin and insulin resistance was passed by HOMA- IR. Prostatic specific antigen passed by immune-enzymatic assay. Vitamins were estimated by high performance liquid chromatography. In our study 30 prostate cancer patients aged 60-80years were taken as cases. 30 normal age matched disease free person were taken as controls in both groups, Insulin resistance and antioxidant vitamin status was studied. In the present study, the value of HOMA-IR was (P <0.05 is significantly higher compare to controls. Serum vitamin E and vitamin C values for cases was reduced (P <0.05 significantly lower than controls. The development of prostate cancer is a multistep process. Hyperinsulinemia associated with insulin resistance may play a role in pathogenesis of prostate cancer. Prostate cancer cells generate high levels a ROS. [Int J Res Med Sci 2014; 2(2.000: 643-646

  15. Swallowing therapy and progressive resistance training in head and neck cancer patients undergoing radiotherapy treatment

    DEFF Research Database (Denmark)

    Fredslund Hajdu, Sara Vinther; Wessel, Irene; Johansen, Christoffer

    2017-01-01

    BACKGROUND: Head and neck cancer (HNC) patients are often challenged by treatment induced dysphagia and trismus. Traditionally, rehabilitation is initiated when loss of function has already occurred. There is increasing evidence that it is of benefit to patients to initiate an early rehabilitation...... process before and during treatment. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain and weight loss. The aim of the trial is to investigate the effects of swallowing and mouth-opening exercises combined with progressive resistance training (PRT...... that exercise according to protocol is tolerable and feasible....

  16. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies.

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

    2016-04-12

    Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development.

  17. Endocrine and immune responses to resistance training in prostate cancer patients.

    Science.gov (United States)

    Galvão, D A; Nosaka, K; Taaffe, D R; Peake, J; Spry, N; Suzuki, K; Yamaya, K; McGuigan, M R; Kristjanson, L J; Newton, R U

    2008-01-01

    This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

  18. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    Science.gov (United States)

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  19. Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil.

    Science.gov (United States)

    Cardoso, Nayara Torres; Santos, Bárbara Araújo; Barbosa, André Victor; Superti, Silvana Vargas; Teixeira, Lúcia Martins; Neves, Felipe Piedade Gonçalves

    2017-03-01

    We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.

  20. Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide : A non-cross-resistant schedule

    NARCIS (Netherlands)

    Groen, HJM; Fokkema, E; Biesma, B; Kwa, B; van Putten, JWG; Postmus, PE; Smit, EF

    1999-01-01

    Purpose: To evaluate the efficacy of paclitaxel and carboplatin (PC) in small-cell lung cancer (SCLC) patients resistant to cyclophasphamide, doxorubicin, and etoposide (CDE). Patients and Methods: We performed a phase II study with PC in SCLC patients who relapsed within 3 months after first-line t

  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. Docetaxel Rechallenge in a Heavily Pretreated Patient With Castration-Resistant Prostate Cancer

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    Di Lorenzo, Giuseppe; Pagliuca, Martina; Perillo, Teresa; Benincasa, Alfonso; Bosso, Davide; De Placido, Sabino; Buonerba, Carlo

    2016-01-01

    Abstract Chemotherapy agents for patients with metastatic castration-resistant prostate cancer (mCRPC) include docetaxel and cabazitaxel. Although docetaxel is approved in the first-line treatment setting, a few studies have shown that selected patients can benefit from docetaxel rechallenge. We, here, report the case of a heavily pretreated mCRPC patient who reported clinical benefit from receiving docetaxel after previous exposure to docetaxel, cabazitaxel, abiraterone, and enzalutamide. After 4 cycles of treatment, patient's performance status had improved to 1, the hemoglobin level was 12.9 g/dL and his serum prostate specific antigen levels were reduced by >70%, with no treatment-related adverse events. Although docetaxel rechallenge is a therapeutic option for selected patients, the risk of cumulative toxicity described in literature must be carefully considered. As the risk of cabazitaxel-related cumulative toxicity is probably lower, retreatment with cabazitaxel rather than docetaxel may also be an option in the setting of heavily pretreated mCRPC patients. PMID:27057826

  3. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...

  4. Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists.

    Science.gov (United States)

    Garcia, Jorge A

    2011-03-01

    Sipuleucel-T represents a novel immunotherapeutic compound designed to stimulate an immune response against castration-resistant prostate cancer (CRPC). Sipuleucel-T is an autologous active cellular immunotherapy product, which includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor. Despite the lack of prostate-specific antigen and objective response, a recent phase III randomized trial demonstrated a significant improvement in overall survival in asymptomatic and minimally symptomatic CRPC patients. This review summarizes the clinical development of Sipuleucel-T in CRPC that led to the regulatory approval of this compound in the USA.

  5. Cabazitaxel in patients with metastatic castration-resistant prostate cancer: results of a compassionate use program in the Netherlands

    NARCIS (Netherlands)

    Wissing, M.D.; Oort, I.M. van; Gerritsen, W.R.; Eertwegh, A.J. van den; Coenen, J.L.; Bergman, A.M.; Gelderblom, H.

    2013-01-01

    BACKGROUND: Cabazitaxel has been reimbursed as a second-line therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC) in the Netherlands since 2011. Before reimbursement was available, cabazitaxel was provided through a Compassionate Use Program (CUP). We report the results of

  6. Phase II Study of Pomalidomide in Patients with Castration-Resistant Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Robert J., E-mail: robert.amato@uth.tmc.edu [Memorial Hermann Cancer Center, University of Texas, 6410 Fannin Street, Suite 830, Houston, TX 77030 (United States); Glode, L. Michael [Health Science Center, University of Colorado, Denver, CO 80217 (United States); University of Colorado Cancer Center, Aurora, CO 80045 (United States); Podolnick, Jeremy [Memorial Hermann Cancer Center, University of Texas, 6410 Fannin Street, Suite 830, Houston, TX 77030 (United States); Knight, Robert [Celgene Corporation, Summit, NJ 07901-3915 (United States); Crawford, David [Health Science Center, University of Colorado, Denver, CO 80217 (United States); University of Colorado Cancer Center, Aurora, CO 80045 (United States)

    2011-09-02

    Pomalidomide is a distinct immunomodulatory agent that also displays anti-proliferative and proapoptotic activity. The purpose of this study was to assess the efficacy and safety of pomalidomide for the treatment of chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (CRPC). Methods: Pomalidomide was administered orally in doses of 1 or 2 mg/day without interruption. Follow ups were conducted every 4 weeks with evaluation of study outcomes at 12 weeks. The principal study outcomes were PSA response, time to progression (TTP) using RECIST, overall survival (OS), and safety. A total of 32 patients were enrolled: 15 in the 1 mg/day cohort (median baseline PSA level of 12.30 ng/mL [0.8–236.0]), and 17 in the 2 mg/day cohort (median baseline PSA level of 12.50 ng/mL [0.6–191.8]). Results: In the 1 mg cohort disease was stabilized for ≥28 days in eight patients, and median TTP was 2.90 months. In the 2 mg cohort, PSA decreased ≥50% in three patients, disease was stabilized for ≥28 days in seven patients, and median TTP was 5.87 months. Toxicity in both cohorts was predominantly grade 1 or 2; 2 grade 3 toxicity (fatigue) occurred in the 1 mg cohort, and 5 grade 3 toxicities (chest pain, diarrhea, epigastric pain, impaction, pain) occurred in the 2 mg cohort. One grade 4 toxicity of cardiac ischemia occurred. Conclusions: Pomalidomide shows promising activity in patients with CRPC and has an acceptable safety profile.

  7. Oral pristinamycin for the treatment of resistant Gram-positive infections in patients with cancer: Evaluation of clinical outcomes.

    Science.gov (United States)

    Teng, J C; Lingaratnam, S M; Trubiano, J A; Thursky, K A; Slavin, M A; Worth, L J

    2016-05-01

    Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal/pelvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.

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

    DEFF Research Database (Denmark)

    Lønbro, Simon

    2014-01-01

    resistance training on lean body mass in post-treatment cancer patients. A comprehensive literature search was conducted and ultimately 12 studies were included. Methodological quality of the included studies was evaluated using the PEDro scale and the effect of progressive resistance training was reported......Loss of lean body mass is a common problem in many post-treatment cancer patients and may negatively affect physical capacity in terms of maximal muscle strength and functional performance. The purpose of this study was to systematically review the scientific evidence on the effect of progressive...... as the range of mean changes among RCTs and non-RCTs. Six RCTs and six non-RCTs were included in the study. In the RCTs the change in lean body mass in the progressive resistance training groups relative to control groups ranged from -0.4% to 3.9%, and in four of six trials the training effect...

  9. Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists

    OpenAIRE

    Garcia, Jorge A.

    2011-01-01

    Sipuleucel-T represents a novel immunotherapeutic compound designed to stimulate an immune response against castration-resistant prostate cancer (CRPC). Sipuleucel-T is an autologous active cellular immunotherapy product, which includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphatase and granulocyte-macrophag...

  10. Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center

    Directory of Open Access Journals (Sweden)

    M Sengar

    2015-01-01

    Full Text Available BACKGROUND: Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. AIMS: To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. SETTINGS AND DESIGN: This is a retrospective analysis from a tertiary care cancer center. MATERIALS AND METHODS: From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. RESULTS: A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%. CONCLUSIONS: The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms.

  11. Spontaneous T-cell responses against peptides derived from the Taxol resistance-associated gene-3 (TRAG-3) protein in cancer patients

    DEFF Research Database (Denmark)

    Meier, Anders; Hadrup, Sine Reker; Svane, Inge Marie

    2005-01-01

    Expression of the cancer-testis antigen Taxol resistance - associated gene-3 (TRAG-3) protein is associated with acquired paclitaxel ( Taxol) resistance, and is expressed in various cancer types; e. g., breast cancer, leukemia, and melanoma. Thus, TRAG-3 represents an attractive target...... for immunotherapy of cancer. To identify HLA-A* 02.01 - restricted epitopes from TRAG-3, we screened cancer patients for spontaneous cytotoxic T-cell responses against TRAG-3 - derived peptides. The TRAG-3 protein sequence was screened for 9mer and 10mer peptides possessing HLA-A* 02.01 - binding motifs. Of 12...... potential binders, 9 peptides were indeed capable of binding to the HLA-A* 02.01 molecule, with binding affinities ranging from strong to weak binders. Subsequently, lymphocytes from cancer patients ( 9 breast cancer patients, 12 melanoma patients, and 13 patients with hematopoietic malignancies) were...

  12. Radium-223 dichloride: illustrating the benefits of a multidisciplinary approach for patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Renzulli II JF

    2015-06-01

    Full Text Available Joseph F Renzulli II, Jennifer Collins, Anthony Mega Genitourinary Multidisciplinary Clinic, The Miriam Hospital, Providence, RI, USAAbstract: Improving options for patients with metastatic castration-resistant prostate cancer (mCRPC provide latitude in designing treatment plans that meet patients' medical needs and personal goals. The field's rapid evolution opens avenues for contributions by multiple medical specialties and requires considering more options to ensure that each patient receives the most appropriate care. A multidisciplinary clinic (MDC focusing on patients with cancers of the genitourinary tract demonstrates an efficient and cost-effective means of integrating the diverse professional knowledge and skills needed to develop an optimal patient treatment plan. As a guide to establishing an MDC for patients with mCRPC, this article describes the operation of the Genitourinary MDC at The Miriam Hospital in Providence, RI – specifically, the successful incorporation of radium-223 dichloride (radium-223 into the treatment algorithm for men with mCRPC and symptomatic bone metastases. Radium-223 is a new treatment that, unlike earlier radionuclide therapies, has shown a survival advantage in a large randomized phase 3 trial (ALSYMPCA. The overall survival benefit was comparable to that of newer immuno- and hormonal therapies in similar populations. Radium-223 treatment also delayed onset of symptomatic skeletal events. Both benefits were independent of prior docetaxel therapy or concurrent bisphosphonate use. In our clinic, radium-223 is used primarily to extend patient survival. Patient selection, patient management, and treatment sequencing are discussed here in the context of a multidisciplinary environment. Keywords: radium-223 dichloride, prostate cancer, castration-resistant prostate cancer, multidisciplinary clinic, best practices

  13. Sipuleucel-T for the Treatment of Patients With Metastatic Castrate-resistant Prostate Cancer: Considerations for Clinical Practice.

    Science.gov (United States)

    Pieczonka, Christopher M; Telonis, Dimitrios; Mouraviev, Vladimir; Albala, David

    2015-01-01

    Sipuleucel-T treatment is associated with a significant and consistent survival benefit in patients with metastatic castrate-resistant prostate cancer. Most adverse events are infusion related, manageable, and of short duration. Early screening and diagnosis of metastatic disease is important, as the greatest survival benefit may occur in patients with a lower disease burden. The short duration of sipuleucel-T treatment facilitates the use of subsequent therapies. Sipuleucel-T is now being used in the clinic for patients with a lower disease burden. We present our own experience with the use of sipuleucel-T in the setting of a large urology practice.

  14. 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

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... 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......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

  15. Annexin A3 Is a Potential Predictor of Platinum Resistance in Epithelial Ovarian Cancer Patients in a Prospective Cohort.

    Science.gov (United States)

    Jin, Ying; Feng, Li-Ping; Jiang, Xiang; Wang, Yong-Xue; Yin, Jie; Yang, Zi-Ping; Li, Yan; Pan, Ling-Ya

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies and is rarely cured in the recurrent setting, mainly because of progressive chemoresistance, especially platinum resistance. In our previous studies, the platinum-resistance-related protein, annexin A3, was selected by comparative proteomics. In this study, we detected serum annexin A3 levels using a self-developed chemiluminescence immunoassay kit in a prospective EOC patient cohort. We also evaluated the capacity of serum annexin A3 levels to predict platinum resistance. Serum annexin A3 levels in healthy women exhibited a similar normal distribution (Z=0.723, P=0.673), allowing determination of a normal cutoff level of 0.11-1.45 ng/mL. Of the 89 EOC patients, 21 were platinum resistant and 68 were platinum sensitive. Residual disease after primary surgery (p=0.004) and serum annexin A3 levels (p=0.036) were both independent factors associated with platinum resistance. The AUC was 0.733 (95% confidence interval (CI), 0.627-0.823). The optimal cutoff value for serum annexin A3 levels was 2.05 ng/mL. Multivariate logistic analysis showed that expression of annexin A3 as assessed by immunohistochemistry (P=0.005) and residual tumor size (P=0.000) had a significant influence on platinum resistance. The AUC of ROC curve of annexin A3 expression by immunohistochemistry was 0.664 (95% CI, 0.554-0.763) and the cut off value was ">=moderate scores". In conclusion, we demonstrate that annexin A3 is a secreted protein that may be measured in the peripheral blood using a self-developed, chemiluminescence immunoassay kit. Serum annexin A3 levels may be a potential predictor of platinum resistance in epithelial ovarian cancer patients.

  16. Breast Cancer Resistance Protein Expression and 5-Fluorouracil Resistance

    Institute of Scientific and Technical Information of China (English)

    JIAN-HUI YUAN; ZHI-XIONG ZHUANG; JIN-QUAN CHENG; LONG-YUAN JIANG; WEI-DONG JI; LIANG-FENG GUO; JIAN-JUN LIU; XING-YUN XU; JING-SONG HE; XIAN-MING WANG

    2008-01-01

    To filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. Methods MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immununohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens. Results MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P=0.8124, P<0.01). Condusion Resistance to 5-Fu can be mediated by BCRP. Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

  17. The Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Mouraviev, Vladimir; Mariados, Neil; Albala, David; Concepcion, Raoul S; Shore, Neal D; Sims, Robert B; Emberton, Mark; Pieczonka, Christopher M

    2014-01-01

    Immunotherapy encourages the recipient's own immune response to destroy cancer cells, and current evidence suggests that immunotherapies may be most beneficial in early metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first therapeutic cancer vaccine to be approved by both the US Food and Drug Administration and European Medicines Agency for the treatment of asymptomatic or minimally symptomatic mCRPC. Combining immunotherapy with other treatments may have potent anticancer effects; cytoreductive therapies can release tumor antigens and promote a proinflammatory environment that could augment immunotherapies. However, some cytoreductive agents or coadministered drugs may be immunosuppressive. Understanding these interactions between different mCRPC treatment modalities may offer further potential to improve patient outcomes.

  18. Draft Genome Sequence of Erythromycin-Resistant Streptococcus gallolyticus subsp. gallolyticus NTS 31106099 Isolated from a Patient with Infective Endocarditis and Colorectal Cancer.

    Science.gov (United States)

    Kambarev, Stanimir; Caté, Clément; Corvec, Stéphane; Pecorari, Frédéric

    2015-04-23

    Streptococcus gallolyticus subsp. gallolyticus is known for its close association with infective endocarditis and colorectal cancer in humans. Here, we report the draft genome sequence of highly erythromycin-resistant strain NTS 31106099 isolated from a patient with infective endocarditis and colorectal cancer.

  19. Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Randomized studies have shown improved survival with the combination of docetaxel (D) and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively investigated whether coadministration of low-dose glucocorticoids has clinical benefits.......001). P did not influence progression-free survival (P = 0.692, log-rank test) or overall survival when adjusting for baseline levels of hemoglobin, alkaline phosphatase, lactate dehydrogenase, prostate-specific antigen, and Eastern Cooperative Oncology Group performance status (hazard ratioP = 0.98, 95...

  20. Differentiated thyroid cancer in patients with resistance to thyroid hormone syndrome. A novel case and a review of the literature.

    Science.gov (United States)

    Vinagre, João; Borges, Fátima; Costa, António; Alvelos, Maria Inês; Mazeto, Glaúcia; Sobrinho-Simões, Manuel; Soares, Paula

    2014-01-01

    Resistance to thyroid hormone (RTH) represents a syndrome in which patients present elevated circulating thyroid hormones in the presence of non-suppressed TSH. We report a novel case where a patient with RTH presented a differentiated thyroid cancer. A19 year-old female had been referred due to thyroid disease that disclosed features characteristic of a RTH. During the follow up it was detected a follicular tumor that led to the recommendation for thyroid surgical ablation, where an incidental papillary thyroid microcarcinoma (mPTC) was found. The increase of thyroglobulin (TG) levels following thyroid removal referred the patient for radioiodine treatment. Post-treatment, it was detected jugular adenopathies and the patient was subjected to cervical lymph node drainage where metastases of the mPTC were found. RTH syndrome was confirmed by the detection of a THRB germline mutation. A BRAF mutation was also found in the mPTC but not detected in the follicular adenoma or normal adjacent tissue. The young age of the patient, the rarity of BRAF mutations in childhood and the high dissemination of the malignancy, lead us to the speculation that increased TSH stimulation in a RTH background and oncogenic activation of BRAF could have served as (co) drivers and might have triggered an advanced stage of the neoplastic disease. These findings together with a review of published cases add novel information to the management of RTH patients with differentiated thyroid cancer.

  1. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Okuma Y

    2015-06-01

    Full Text Available Yusuke Okuma,1,2 Yuichiro Tanaka,3 Tina Kamei,1 Yukio Hosomi,1 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 2Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, 3Department of Ophthalmology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan Abstract: Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient’s remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash. Keywords: lung cancer, ALK rearrangement, alectinib, choroidal metastasis, molecular targeted

  2. SERPINB3 in the chicken model of ovarian cancer: a prognostic factor for platinum resistance and survival in patients with epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Whasun Lim

    Full Text Available Serine protease inhibitors (SERPINs appear to be ubiquitously expressed in a variety of species and play important roles in pivotal physiological processes such as angiogenesis, immune responses, blood coagulation and fibronolysis. Of these, squamous cell carcinoma antigen 1 (SCCA1, also known as a SERPINB3, was first identified in squamous cell carcinoma tissue from the cervix of women. However, there is little known about the SERPINB3 expression in human epithelial ovarian cancer (EOC. Therefore, in the present study, we investigated the functional role of SERPINB3 gene in human EOC using chickens, the most relevant animal model. In 136 chickens, EOC was found in 10 (7.4%. SERPINB3 mRNA was induced in cancerous, but not normal ovaries of chickens (P<0.01, and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. Further, several microRNAs, specifically miR-101, miR-1668 and miR-1681 were discovered to influence SERPINB3 expression via its 3'-UTR which suggests that post-transcriptional regulation influences SERPINB3 expression in chickens. SERPINB3 protein was localized predominantly to the glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%, 66 (60.6% and 28 (25.7% patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR; odds ratio, 5.94; 95% Confidence Limits, 1.21-29.15, and for poor progression-free survival (PFS; adjusted HR; hazard ratio, 2.07; 95% CI; confidence interval, 1.03-4.41. Therefore, SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.

  3. Docetaxel Rechallenge in a Heavily Pretreated Patient With Castration-Resistant Prostate Cancer: A Case Report and Review of Literature.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Pagliuca, Martina; Perillo, Teresa; Benincasa, Alfonso; Bosso, Davide; De Placido, Sabino; Buonerba, Carlo

    2016-04-01

    Chemotherapy agents for patients with metastatic castration-resistant prostate cancer (mCRPC) include docetaxel and cabazitaxel. Although docetaxel is approved in the first-line treatment setting, a few studies have shown that selected patients can benefit from docetaxel rechallenge.We, here, report the case of a heavily pretreated mCRPC patient who reported clinical benefit from receiving docetaxel after previous exposure to docetaxel, cabazitaxel, abiraterone, and enzalutamide.After 4 cycles of treatment, patient's performance status had improved to 1, the hemoglobin level was 12.9 g/dL and his serum prostate specific antigen levels were reduced by >70%, with no treatment-related adverse events.Although docetaxel rechallenge is a therapeutic option for selected patients, the risk of cumulative toxicity described in literature must be carefully considered.As the risk of cabazitaxel-related cumulative toxicity is probably lower, retreatment with cabazitaxel rather than docetaxel may also be an option in the setting of heavily pretreated mCRPC patients.

  4. Characterization of Ciprofloxacin-Resistant and Ciprofloxacin-Susceptible Uropathogenic Escherichia coli Obtained from Patients with Gynecological Cancer.

    Science.gov (United States)

    Capett, Muniqui S; Vollú-Silva, Patricia; Melchiades, Vanessa A; Bokehi, Luciana C; Araújo, Fernanda M; Martins, Ianick Souto; Neves, Felipe P G; Gonzalez, Alice G M; Oswald, Eric; de Paula, Geraldo R; Teixeira, Lenise A

    2016-11-01

    The objective of this work was to assess the genetic characteristics of uropathogenic Escherichia coli, ciprofloxacin resistance or susceptibility, obtained from patients with gynecological cancer and urinary tract infection (UTI). Seventy-seven E. coli ciprofloxacin-resistant isolates and 38 ciprofloxacin-susceptible were analyzed by polymerase chain reaction (PCR) to determine the phylogenetic groups, virulence factors as iucC, fyuA, hlyC, cnf1 genes, and pks pathogenicity island. The presence of genes related to ciprofloxacin resistance such as qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA, and the sequencing of DNA gyrase genes and topoisomerase IV were determined. The genetic profile of the isolates was determined by pulsed-field gel electrophoresis (PFGE). Statistical analysis was performed using Fisher's exact test and Chi-square test. Phylogenetic group B2 was the most prevalent although a great genetic diversity was observed by PFGE. Only genes associated to siderophores were found in ciprofloxacin-resistant isolates; however, in ciprofloxacin-susceptible isolates, genes related to siderophores and toxin, were detected. Additionally qnrB was detected in both populations, ciprofloxacin resistant and susceptible. DNA mutations in gyrA were Ser-83-Leu and Asp-87-Asn and in parC were Ser-80-Ile and Glu-84-Val, Glu-84-Lys. In conclusion, it was observed a high prevalence of qnrB in the population studied; in addition, it was the first time the pks island was observed only in ciprofloxacin-susceptible isolates.

  5. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Harrison MR

    2013-01-01

    Full Text Available Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J GeorgeDuke Cancer Institute, Durham, NC, USABackground: Radium-223 chloride (223Ra; Alpharadin is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153, 223Ra delivers a high quantity of energy per track length with short tissue penetration.Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile.Methods: Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.Conclusion: Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab, which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153, which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC. Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel

  6. Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2014-01-01

    Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

  7. Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naive Patients with Metastatic Castration Resistant Prostate Cancer

    NARCIS (Netherlands)

    Smith, M.R.; Rathkopf, D.E.; Mulders, P.F.A.; Carles, J.; Poppel, H. Van; Li, J.; Kheoh, T.; Griffin, T.W.; Molina, A.; Ryan, C.J.

    2015-01-01

    PURPOSE: Metastatic castration resistant prostate cancer primarily affects elderly men. In this post hoc analysis we investigated the safety and efficacy of abiraterone acetate in elderly (age 75 years or greater) and younger (less than 75 years) patient subgroups at the prespecified interim analysi

  8. The effect of BIM deletion polymorphism on intrinsic resistance and clinical outcome of cancer patient with kinase inhibitor therapy.

    Science.gov (United States)

    Ying, Hou-Qun; Chen, Jie; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Deng, Qi-Wen; Sun, Hui-Ling; Liu, Xian; Wang, Shu-Kui

    2015-06-15

    A common deletion polymorphism within B-cell chronic lymphocytic leukemia-lymphoma like 11 gene (BIM) was deemed to be a genetic cause leading to compromised kinase inhibitor therapeutic efficacy in cancer individuals. However, the results reported were not consistent. Thus, a comprehensive meta-analysis containing 12 eligible studies including 1,532 Asian patients was conducted to investigate a steady and reliable conclusion. The results showed that BIM deletion polymorphism was significantly associated with tyrosine kinase inhibitor (TKI) clinical efficacy in term of response rate (Ph = 0.349, HR = 0.438, 95%CI = 0.274-0.699) and disease control rate (Ph = 0.941, HR = 0.370, 95%CI = 0.202-0.678) in EGFR-mutated NSCLC population, not in CML and HCC subgroups. Additionally, EGFR-mutated NSCLC patient harbored BIM deletion polymorphism was associated with a shorter progression-free survival (PFS) than those with BIM wild polymorphism (Ph = 0.580, adjusted HR = 2.194, 95%CI = 1.710-2.814). However, no significant association was examined between BIM deletion polymorphism and overall survival (OS) and toxic adverse events in EGFR-mutated NSCLC population and it was not associated with PFS and OS in HCC subgroup. These findings revealed that BIM deletion polymorphism might be a genetic cause of intrinsic resistance to TKI therapy and it could be emerged as an independent predictor to identify patients who would benefit from TKI targeted therapy in EGFR-mutated NSCLC.

  9. Sustained complete response to CTLA-4 blockade in a patient with metastatic, castration-resistant prostate cancer.

    Science.gov (United States)

    Graff, Julie N; Puri, Sachin; Bifulco, Carlo B; Fox, Bernard A; Beer, Tomasz M

    2014-05-01

    We present the case of a man with metastatic, castration-resistant prostate cancer, who had a complete prostate-specific antigen (PSA) response after 2½ doses of ipilimumab. His treatment course was complicated by diarrhea and autoimmune hepatitis, both of which resolved within 4 months. Sera and biopsy specimens were accessed, and sera from pretreatment and day 113 were analyzed. Augmented antibody responses were detected against 11 potential tumor antigens, with responses ranging from 5- to 20-fold in day 113 sera compared with baseline. Genes that were targets of a strong antibody response (arbitrarily set at 10-fold or greater increase) were analyzed by real-time PCR for expression in the tumor biopsy cDNA. Of the top 5 genes, only 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) could be identified in the amplified tumor biopsy cDNA. Using an antibody to HIBCH, immunohistochemical analysis documented strong expression of the protein. Together, these data suggest that an augmented antibody response to HIBCH, an antigen that was expressed by the patient's prostate cancer, could have contributed to the clinical response. After 16 months of PSA stability, he discontinued his androgen-suppression therapy. With the return of his testosterone, his PSA increased slightly, likely originating from his intact prostate. He has been disease free for the past 6 years without any additional therapy.

  10. The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

    Directory of Open Access Journals (Sweden)

    Crawford Jeffrey

    2010-04-01

    Full Text Available Abstract Background The Lung Cancer Exercise Training Study (LUNGEVITY is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak, patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC patients. Methods/Design Using a single-center, randomized design, 160 subjects (40 patients/study arm with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1 aerobic training alone, (2 resistance training alone, (3 the combination of aerobic and resistance training, or (4 attention-control (progressive stretching. The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks, social interaction (participants will receive one-on-one instruction, and duration (30-45 mins/session. The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs (e.g., quality of life, fatigue, depression, etc. and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function. All endpoints will be assessed at baseline and postintervention (16 weeks. Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes

  11. {sup 11}C-Choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, UO Medicina Nucleare PAD. 30, Bologna (Italy); Castellucci, Paolo; Graziani, Tiziano; Renzi, Riccardo; Fanti, Stefano [University of Bologna, Service of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna (Italy); Schiavina, Riccardo; Borghesi, Marco; Brunocilla, Eugenio [University of Bologna, Department of Urology, S. Orsola-Malpighi Hospital, Bologna (Italy); Di Tullio, Piergiorgio; Ardizzoni, Andrea [University of Bologna, Department of Oncology, S. Orsola-Malpighi Hospital, Bologna (Italy)

    2016-01-15

    To investigate the role of {sup 11}C-choline PET/CT for evaluating the response to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel in comparison with PSA response. Inclusion criteria were (a) proven mCRPC, (b) docetaxel as first line of chemotherapy (docetaxel 75 mg/m{sup 2} + prednisone 5 mg), and (c) {sup 11}C-choline PET/CT and PSA values assessed before and after docetaxel administration. A total of 61 patients were retrospectively enrolled (mean age 68.9 years, range 57 - 84 years). {sup 11}C-Choline PET/CT was performed at baseline before docetaxel treatment (PET1) and after the end of treatment (PET2). PSA values were measured before treatment (PSA1) and after treatment (PSA2). PET2 was reported as complete response (CR), partial response (PR) or stable disease (SD). Progressive disease (PD) was considered if a new lesion was seen. PSA trend was calculated from the change in absolute values between PSA1 and PSA2. A decrease of ≥50 % between PSA1 and PSA2 was considered a PSA response. Clinical, radiological and laboratory follow-up ranged from 6 to 53 months (mean 13.5 months). Of the 61 patients, 40 (65.5 %) showed PD on PET2, 13 (21.3 %) showed SD, 2 (3.4 %) showed PR, and 6 (9.8 %) showed CR. An increasing PSA trend was seen in 29 patients (47.5 %) and a decreasing PSA trend in 32 patients (52.5 %). A PSA response of ≥50 % was seen in 25 patients (41 %). Radiological PD was seen in 23 of the 29 patients (79.3 %) with an increasing PSA trend, in 16 of the 32 patients (50 %) with a decreasing PSA trend, and in 11 of the 25 patients (44 %) with a PSA response of ≥50 %. In the multivariate statistical analysis, the presence of more than ten bone lesions detected on PET1 was significantly associated with an increased probability of PD on PET2. No association was observed between PSA level and PD on PET2. Our results suggest that an increasing PSA trend measured after docetaxel treatment could be

  12. Resistance to Trastuzumab in Breast Cancer.

    Science.gov (United States)

    Pohlmann, Paula R; Mayer, Ingrid A; Mernaugh, Ray

    2009-12-15

    HER2 is a transmembrane oncoprotein encoded by the HER2/neu gene and is overexpressed in approximately 20 to 25% of invasive breast cancers. It can be therapeutically targeted by trastuzumab, a humanized IgG1 kappa light chain monoclonal antibody. Although trastuzumab is currently considered one of the most effective treatments in oncology, a significant number of patients with HER2-overexpressing breast cancer do not benefit from it. Understanding the mechanisms of action and resistance to trastuzumab is therefore crucial for the development of new therapeutic strategies. This review discusses proposed trastuzumab mode of action as well as proposed mechanisms for resistance. Mechanisms for resistance are grouped into four main categories: (1) obstacles preventing trastuzumab binding to HER2; (2) upregulation of HER2 downstream signaling pathways; (3) signaling through alternate pathways; and (4) failure to trigger an immune-mediated mechanism to destroy tumor cells. These potential mechanisms through which trastuzumab resistance may arise have been used as a guide to develop drugs, presently in clinical trials, to overcome resistance. The mechanisms conferring trastuzumab resistance, when completely understood, will provide insight on how best to treat HER2-overexpressing breast cancer. The understanding of each mechanism of resistance is therefore critical for the educated development of strategies to overcome it, as well as for the development of tools that would allow definitive and efficient patient selection for each therapy. (Clin Cancer Res 2009;15(24):7479-91).

  13. Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated with Eribulin

    NARCIS (Netherlands)

    Van Hasselt, J. G C; Gupta, A.; Hussein, Z.; Beijnen, J. H.; Schellens, J. H M; Huitema, A. D R

    2015-01-01

    Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant

  14. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Chi, Kim N; Spratlin, Jennifer; Kollmannsberger, Christian; North, Scott; Pankras, Catherine; Gonzalez, Martha; Bernard, Apexa; Stieltjes, Hans; Peng, Lixian; Jiao, James; Acharya, Milin; Kheoh, Thian; Griffin, Thomas W; Yu, Margaret K; Chien, Caly; Tran, Nam Phuong

    2015-12-01

    Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients. Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0.5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety.

  15. Complete response to ethnylestradiol prolonged for almost two years in patients with castration-resistant prostate cancer.

    Science.gov (United States)

    Hongo, Hiroshi; Kosaka, Takeo; Oya, Mototsugu

    2014-11-01

    An 80-year-old man with an elevated prostate-specific antigen (PSA) level of 120 ng/mL) presented to the hospital in February 2011. A prostate needle biopsy was performed, and pathological examination revealed prostatic adenocarcinoma. The Gleason score was 4+5=9. Computed tomography revealed metastases of the pelvic lymph nodes. Combined androgen blockade was started. The PSA concentration decreased to 1.68 ng/mL, but started increasing again in August 2012 to 6.08 ng/mL. Although bicalutamide was discontinued due to antiandrogen withdrawal syndrome, the PSA concentration increased even more. The PSA concentration reached 21.62 ng/mL in September 2012, at which time ethnylestradiol was started. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years. To our knowledge, this is first case report describing a complete response to ethnylestradiol that lasted for almost 2 years in a patient with castration-resistant prostate cancer.

  16. 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

  17. State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012.

    Science.gov (United States)

    Sartor, Oliver

    2012-01-01

    Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future

  18. Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

    OpenAIRE

    Verzoni, Elena; De Giorgi, Ugo; Derosa, Lisa; Caffo, Orazio; Boccardo, Francesco; Facchini, Gaetano; Porcu, Luca; Vincenzo, Fabio De; Zaniboni, Alberto; Chiuri, Vincenzo Emanuele; Fratino, Lucia; Santini, Daniele; Adamo, Vincenzo; De Vivo, Rocco; Dinota, Angelo

    2016-01-01

    We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143...

  19. Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors

    Directory of Open Access Journals (Sweden)

    Ribeiro Gomes J

    2015-05-01

    Full Text Available Jéssica Ribeiro Gomes, Marcelo Rocha S Cruz Antonio Ermirio de Moraes Oncology Center, São Paulo-Brazil Abstract: Tyrosine kinase inhibitors (TKIs targeting the epidermal growth factor receptor (EGFR have shown effectiveness for advanced non-small-cell lung cancer (NSCLC with activating mutations in the EGFR gene. However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. The use of afatinib associated with cetuximab represents a new possibility of therapy following progression on gefitinib or erlotinib. We present two patients who acquired resistance to first-generation TKI and who underwent combination treatment with afatinib plus cetuximab as third-line therapy. Both patients presented partial response, and the time duration of disease control was 8 months and 10 months. The combined use of afatinibplus cetuximab emerges as a new possibility for the treatment of patients with advanced NSCLC harboring mutated EGFR after progression on first-generation EGFR TKIs with consequently acquired resistance to TKIs. Further studies are necessary to consolidate the data. Keywords: lung cancer, non-small-cell lung cancer, EGFR, afatinib, cetuximab, case report 

  20. Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

    2015-10-15

    Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

  1. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial

    NARCIS (Netherlands)

    Basch, E.; Autio, K.; Ryan, C.J.; Mulders, P.; Shore, N.; Kheoh, T.; Fizazi, K.; Logothetis, C.J.; Rathkopf, D.; Smith, M.R.; Mainwaring, P.N.; Hao, Y.; Griffin, T.; Li, S.; Meyers, M.L.; Molina, A.; Cleeland, C.

    2013-01-01

    BACKGROUND: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patie

  2. A proteomic approach links decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer and in human cell lines.

    Science.gov (United States)

    Martinez-Balibrea, Eva; Plasencia, Carmen; Ginés, Alba; Martinez-Cardús, Anna; Musulén, Eva; Aguilera, Rodrigo; Manzano, José Luis; Neamati, Nouri; Abad, Albert

    2009-04-01

    We aimed to gain further understanding of the molecular mechanisms involved in oxaliplatin resistance in colorectal cancer by using a proteomic approach. A 5-fold oxaliplatin-resistant cell line, HTOXAR3, was compared with its parental cell line, HT29, using two-dimensional PAGE. Mass spectrometry, Western blot, and real-time quantitative PCR confirmed the down-regulation of pyruvate kinase M2 (PK-M2) in HTOXAR3 cells. In a panel of eight colorectal cancer cell lines, we found a negative correlation between oxaliplatin resistance and PK-M2 mRNA levels (Spearman r=-0.846, P=0.008). Oxaliplatin exposure in both HT29 and HTOXAR3 led to PK-M2 mRNA up-regulation. PK-M2 mRNA levels were measured by real-time quantitative PCR in 41 tumors treated with oxaliplatin/5-fluorouracil. Tumors with the lowest PK-M2 levels attained the lowest response rates (20% versus 64.5%, P=0.026). High PK-M2 levels were associated with high p53 levels (P=0.032). In conclusion, the data provided clearly link PK-M2 expression and oxaliplatin resistance mechanisms and further implicate PK-M2 as a predictive marker of response in patients with oxaliplatin-treated colorectal cancer.

  3. An Acquired HER2 T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

    Science.gov (United States)

    Hanker, Ariella B; Red Brewer, Monica; Sheehan, Jonathan H; Koch, James P; Sliwoski, Gregory R; Nagy, Rebecca; Lanman, Richard; Berger, Michael F; Hyman, David M; Solit, David B; He, Jie; Miller, Vincent; Cutler, Richard E; Lalani, Alshad S; Cross, Darren; Lovly, Christine M; Meiler, Jens; Arteaga, Carlos L

    2017-03-08

    We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2L869R but not HER2L869R/T798I. In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2L869R/T798I-induced signaling and cell growth. Acquisition of HER2T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2L869R is a driver mutation. HER2T798I-mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib.

  4. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  5. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  6. Effects of androgen deprivation therapy and bisphosphonate treatment on bone in patients with metastatic castration-resistant prostate cancer: results from the University of Washington Rapid Autopsy Series.

    Science.gov (United States)

    Morrissey, Colm; Roudier, Martine P; Dowell, Alex; True, Lawrence D; Ketchanji, Melanie; Welty, Christopher; Corey, Eva; Lange, Paul H; Higano, Celestia S; Vessella, Robert L

    2013-02-01

    Qualitative and quantitative bone features were determined in nondecalcified and decalcified bone from 20 predetermined bone sites in each of 44 patients who died with castration-resistant prostate cancer (CRPC), some of which received bisphosphonate treatment (BP) in addition to androgen-deprivation therapy (ADT). Thirty-nine of the 44 patients (89%) had evidence of bone metastases. By histomorphometric analysis, these bone metastases were associated with a range of bone responses from osteoblastic to osteolytic with a wide spectrum of bone responses often seen within an individual patient. Overall, the average bone volume/tissue volume (BV/TV) was 25.7%, confirming the characteristic association of an osteoblastic response to prostate cancer bone metastasis when compared with the normal age-matched weighted mean BV/TV of 14.7%. The observed new bone formation was essentially woven bone, and this was a localized event. In comparing BV/TV at metastatic sites between patients who had received BP treatment and those who had not, there was a significant difference (28.6% versus 19.3%, respectively). At bone sites that were not invaded by tumor, the average BV/TV was 10.1%, indicating significant bone loss owing to ADT that was not improved (11%) in those patients who had received BPs. Surprisingly, there was no significant difference in the number of osteoclasts present at the metastatic sites between patients treated or not treated with BPs, but in bone sites where the patient had been treated with BPs, giant osteoclasts were observed. Overall, 873 paraffin-embedded specimens and 661 methylmethacrylate-embedded specimens were analyzed. Our results indicate that in CRPC patients, ADT induces serious bone loss even in patients treated with BP. Furthermore, in this cohort of patients, BP treatment increased BV and did not decrease the number of osteoclasts in prostate cancer bone metastases compared with bone metastases from patients who did not receive BP.

  7. IL-33 facilitates endocrine resistance of breast cancer by inducing cancer stem cell properties.

    Science.gov (United States)

    Hu, Haiyan; Sun, Jiaxing; Wang, Chunhong; Bu, Xiangmao; Liu, Xiangping; Mao, Yan; Wang, Haibo

    2017-02-16

    Breast cancers with estrogen receptor (ER) expressions account for the majority of all clinical cases. Due to hormone therapy with tamoxifen, prognoses of patients with ER-positive breast cancer are significantly improved. However, endocrine resistance to tamoxifen is common and inevitable, leading to compromised efficacy of hormone therapy. Herein, we identify a crucial role of IL-33 in inducing endocrine resistance of breast cancer. IL-33 overexpression in breast cancer cells results in resistance to tamoxifen-induced tumor growth inhibition, while IL-33 knockdown corrects this problem. Mechanistically, IL-33 induces breast cancer stem cell properties evidenced by mammosphere formation and xenograft tumorigenesis, as well as expression of cancer stem cell genes including ALDH1A3, OCT4, NANOG and SOX2. In breast cancer patients, higher serum IL-33 levels portend advanced clinical stages, poorly differentiated cancer cells and tumor recurrence. IL-33 expression levels in patients' freshly isolated breast cancer cells predicts tamoxifen resistance and cancer stem cell features in individual patient. Collectively, IL-33 induces endocrine resistance of breast cancer by promoting cancer stem cell properties. These findings provide novel mechanisms connecting IL-33 with cancer pathogenesis and pinpoint IL-33 as a promising target for optimizing hormone therapy in clinical practice.

  8. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  9. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer.

    Science.gov (United States)

    Malorni, Luca; Piazza, Silvano; Ciani, Yari; Guarducci, Cristina; Bonechi, Martina; Biagioni, Chiara; Hart, Christopher D; Verardo, Roberto; Di Leo, Angelo; Migliaccio, Ilenia

    2016-09-13

    Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.

  10. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer

    Science.gov (United States)

    Malorni, Luca; Piazza, Silvano; Ciani, Yari; Guarducci, Cristina; Bonechi, Martina; Biagioni, Chiara; Hart, Christopher D.; Verardo, Roberto; Leo, Angelo Di; Migliaccio, Ilenia

    2016-01-01

    Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 − 3.2] p = 1.87e−08 and HR = 2.62 [1.9− 3.5] p = 8.6e−11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted. PMID:27634906

  11. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    Science.gov (United States)

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

  12. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Saad, F.; Fizazi, K.; Jinga, V.; Efstathiou, E.; Fong, P.C.; Hart, L.L.; Jones, R.; McDermott, R.; Wirth, M.; Suzuki, K.; MacLean, D.B.; Wang, L.; Akaza, H.; Nelson, J.; Scher, H.I.; Dreicer, R.; Webb, I.J.; Wit, R. de; Oort, I.M. van

    2015-01-01

    BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resist

  13. Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia.

    Science.gov (United States)

    Freire, M P; de Oliveira Garcia, D; Garcia, C P; Campagnari Bueno, M F; Camargo, C H; Kono Magri, A S G; Francisco, G R; Reghini, R; Vieira, M F; Ibrahim, K Y; Rossi, F; Hajjar, L; Levin, A S; Hoff, P M; Pierrotti, L C; Abdala, E

    2016-04-01

    This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.

  14. Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide

    DEFF Research Database (Denmark)

    Anand, Aseem; Morris, Michael J; Larson, Steven M;

    2016-01-01

    BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the a......BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength......-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall...... alone (C-index 0.73), p = 0.041. CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated...

  15. Depression in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Beyhan Bag

    2014-06-01

    Full Text Available It is not enough to consider treatment and care depression in the oncology that is the most common psychiatric illness in cancer patient affects of cancer treatment and the patient`s quality of life negatively, which is determined through researches in the field. With development of psycho-oncology it has been demonstrated to establish an important link between the cancer patient`s treatment as well as psycho-social support for the patient and psychiatric treatment and care for the if it is needed. With this connection between them it has been proposed to use of bio-psycho-social-model in cancer patient to improve their care. To achieve this goal, it is expected from medical personnel to realize patients psychosocial need und if he/she has a psychiatric disorders or syndromes. For the medical personnel that work in oncology services, it is inevitable to organize in order to raise the awareness of depression in the cancer patients. In the present study, it is focused on raising the awareness of depression in cancer patient for the medical personnel. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 186-198

  16. Time-kill determination of the bactericidal activity of telavancin and vancomycin against clinical methicillin-resistant Staphylococcus aureus isolates from cancer patients.

    Science.gov (United States)

    Rolston, Kenneth Vi; Wang, Weiqun; Nesher, Lior; Smith, Jordan R; Rybak, Michael J; Prince, Randall A

    2017-04-01

    The bactericidal activity of vancomycin and telavancin was compared against 4 clinical methicillin-resistant Staphylococcus aureus isolates recently recovered from cancer patients, using minimum bactericidal concentration (MBC):MIC ratios and time-kill studies. All 4 isolates were susceptible to both agents based on individual MIC values. The 2 methodologies for assessing bactericidal activity produced variable results. Telavancin appeared to have somewhat better bactericidal activity than vancomycin based on narrower MBC:MIC ratios. However, based on the results of the time-kill studies, neither agent demonstrated reliable bactericidal activity (defined as a ≥3 log10 reduction of the starting inoculum at the end of 24hours) against these organisms. These findings might be of some therapeutic importance in certain clinical settings and/or specific patient populations (such as febrile neutropenic patients) in whom potent bactericidal activity is either desired or preferred.

  17. BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis.

    Science.gov (United States)

    Mao, Chen; Liao, Ru-Yan; Qiu, Li-Xin; Wang, Xi-Wen; Ding, Hong; Chen, Qing

    2011-04-01

    Epidemiologic studies have evaluated the association between BRAF mutations and resistance to the treatment of anti-EGFR monoclonal antibodies (MoAb) in patients with metastatic colorectal cancer (mCRC). However, the results are still inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. A total of 11 studies were included in the final meta-analysis. There were seven studies for unselected mCRC patients and four studies for patients with wild type KRAS mCRC. Among unselected mCRC patients, BRAF V600E mutation was detected in 48 of 546 primary tumors (8.8%). The objective response rate (ORR) of patients with mutant BRAF was 29.2% (14/48), whereas the ORR of patients with wild-type BRAF was 33.5% (158/472).The overall RR for ORR of mutant BRAF patients over wild-type BRAF patients was 0.86 (95% CI=0.57-1.30; P=0.48). For patients with KRAS wild-type mCRC, BRAF V600E mutation was detected in 40 of 376 primary tumors (10.6%). The ORR of patients with mutant BRAF was 0.0% (0/40), whereas the ORR of patients with wild-type BRAF was 36.3% (122/336). The pooled RR of mutant BRAF patients over wild-type BRAF patients was 0.14 (95% CI=0.04-0.53; P=0.004). In conclusion, this meta-analysis provides evidence that BRAF V600E mutation is associated with lack of response in wild-type KRAS mCRC treated with anti-EGFR MoAbs. BRAF mutation may be used as an additional biomarker for the selection of mCRC patients who might benefit from anti-EGFR MoAbs therapy.

  18. [Nutrition and cancer patients].

    Science.gov (United States)

    Katsuramaki, T; Hirata, K; Isobe, M

    1998-03-01

    Nutritional therapy for cancer patients includes various objectives such as improvement of cachexia, elucidation of the mechanism of malnutrition, development of therapy for anorexia, nutrition support during chemotherapy or radiotherapy, and inhibition of tumor growth under controlled caloric intake. This review describes recent remarkable developments in nutritional therapy for cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor which induce proteolysis and lipolysis are involved in the cause of malnutrition and cachexia in cancer patients. IL-1 also plays a significant role in the development of cancer anorexia via direct action in the brain. For anorexia therapy, progestogens have been shown to improve appetite and food intake in cancer patients. Moreover, glutamine supplementation improves the host protein metabolism without enhancement of tumor growth during chemotherapy. Among the effects of caloric intake on anticancer therapy, AO-90, a methionine-free intravenous amino acid solution, has been shown to increase the antitumor effect of 5-fluorouracil in clinical studies. From these observations, recent progress in nutritional therapy for cancer patients has been remarkable. Further study of nutritional therapy is required in order to maintain or improve the quality of life of cancer patients in the future.

  19. Efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in castration-resistant prostate cancer patients: report of 102 cases and review of literature.

    Science.gov (United States)

    Matsumoto, Kazuhiro; Tanaka, Nobuyuki; Hayakawa, Nozomi; Ezaki, Taisuke; Suzuki, Kenjiro; Maeda, Takahiro; Ninomiya, Akiharu; Nakamura, So

    2013-12-01

    This retrospective chart review study was conducted to evaluate the efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC) and to determine who would benefit from EMP therapy. EMP was administered at a daily dose of 560 mg to 102 patients as a third-line therapy, who had already received combined androgen blockade (CAB) and subsequent alternative antiandrogen therapy. The responses to EMP after its induction and its toxicity were evaluated. We also analyzed the association between the clinicopathological factors of the patients and their responses to EMP therapy. A reduction in the serum prostate-specific antigen (PSA) 4 weeks after induction was observed in 70 patients (68.6%), while 30 cases (29.4%) achieved more than 50% reduction of PSA. Long-term reduction of PSA from baseline for more than 6 months was observed in 31 patients (30.4%). EMP treatment was discontinued in 11 patients (10.8%) because of side effects (nausea in six patients, gynecomastia in three patients, eruption in one patient, and liver dysfunction in one patient). Multivariate analysis demonstrated that long duration of prior hormonal therapy was an independent favorable factor for reduced PSA levels, long responses, and overall survival. The data suggest that oral EMP administration as a third-line monotherapy is well tolerated and effective to some degree in patients with CRPC who have already received CAB and subsequent alternative antiandrogen therapy. Thus, EMP can be regarded as one treatment option, especially for patients whose prior duration of hormonal therapy was long.

  20. Molecular Indicators of Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2015-12-01

    two components /kits. Briefly, the ProstateCancerSelect (Product No. T-1-520) kit was used to enrich CTC from 5ml blood using magnetic particles coated...in PatientsWithMetastatic Castration-Resistant Prostate Cancer Emmanuel S. Antonarakis, MD; Changxue Lu, PhD; Brandon Luber, ScM ; HaoWang, PhD; Yan

  1. ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer.

    Science.gov (United States)

    Deblois, Geneviève; Smith, Harvey W; Tam, Ingrid S; Gravel, Simon-Pierre; Caron, Maxime; Savage, Paul; Labbé, David P; Bégin, Louis R; Tremblay, Michel L; Park, Morag; Bourque, Guillaume; St-Pierre, Julie; Muller, William J; Giguère, Vincent

    2016-07-12

    Despite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRα, a master regulator of cellular metabolism, and that the expression of ERRα is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRα in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRα-induced metabolic reprogramming promotes survival of lapatinib-resistant cancer cells and demonstrates the potential of ERRα inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer.

  2. Sarcopenia in Cancer Patients.

    Science.gov (United States)

    Chindapasirt, Jarin

    2015-01-01

    Sarcopenia, characterized by a decline of skeletal muscle plus low muscle strength and/or physical performance, has emerged to be an important prognostic factor for advanced cancer patients. It is associated with poor performance status, toxicity from chemotherapy, and shorter time of tumor control. There is limited data about sarcopenia in cancer patients and associated factors. Moreover, the knowledge about the changes of muscle mass during chemotherapy and its impact to response and toxicity to chemotherapy is still lacking. This review aimed to provide understanding about sarcopenia and to emphasize its importance to cancer treatment.

  3. Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Sharp, Adam; Welti, Jonathan; Blagg, Julian; de Bono, Johann S

    2016-09-01

    Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280-2. ©2016 AACRSee related article by Yang et al., p. 4466.

  4. Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer.

    Science.gov (United States)

    Sun, Ruifang; Liu, Zhigang; Wang, Lumin; Lv, Weidong; Liu, Jia; Ding, Caixia; Yuan, Yong; Lei, Guangyan; Xu, Changfu

    2015-09-01

    Paclitaxel can exert therapeutic effects by interacting with microtubules. Stathmin and β-III-tubulin, which have impact on microtubule activity, are believed to be involved in the chemotherapy. The purpose of the present study was to evaluate the associations between stathmin and β-III-tubulin expression and treatment response and survivals in patients with non-small cell lung cancer (NSCLC). Two hundred thirty-eight patients who were treated by platinum-based chemotherapy were enrolled in this study, among them, 111 patients also received paclitaxel treatment. Formalin-fixed and paraffin-embedded tumor tissues were collected for messenger RNA (mRNA) and protein detection. We assessed the associations of the two molecules with treatment response and survival outcome. High level of stathmin exhibited poor response to chemotherapy (for mRNA, P = 0.041; for protein, P = 0.017). Overexpression of stathmin was associated with shorter overall survival (for mRNA, P = 0.012; for protein, P = 0.014) and progression-free survival (for mRNA, P = 0.039; for protein, P = 0.022). Of note, this association was only observed in patients who were treated by both platinum and paclitaxel. Similar effects were not observed for β-III-tubulin. The findings demonstrated that paclitaxel effect may be interfered with stathmin; overexpression of stathmin is a predictive marker for a worse prognosis in patients with NSCLC who were treated by both platinum and paclitaxel chemotherapy.

  5. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  6. A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer.

    Science.gov (United States)

    Noguchi, Masanori; Kakuma, Tatsuyuki; Uemura, Hirotsugu; Nasu, Yasutomo; Kumon, Hiromi; Hirao, Yasuhiko; Moriya, Fukuko; Suekane, Shigetaka; Matsuoka, Kei; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo

    2010-07-01

    Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

  7. [Physiotherapy of cancer patients].

    Science.gov (United States)

    Gomez, Izabella; Szekanecz, Éva; Szekanecz, Zoltán; Bender, Tamás

    2016-07-01

    Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231.

  8. {sup 11}C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco; Ambrosini, Valentina; Boschi, Stefano; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, Department of Haematology Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Castellucci, Paolo [University of Bologna, Nuclear Medicine Unit, Department of Haematology Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Azienda Ospedaliero-Unversitaria di Bologna Policlinico Sant' Orsola-Malpighi, UO di Medicina Nucleare, PAD. 30, Bologna (Italy); Mamede, Marcelo [Universidade Federal de Minas Gerais, Molecular Imaging Center, Belo Horizonte (Brazil); Schiavina, Riccardo; Martorana, Giuseppe [University of Bologna, Department of Urology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant' Orsola-Malpighi, Bologna (Italy); Rubello, Domenico [' Santa Maria della Misericordia' Hospital, Department of Nuclear Medicine and PET/CT Centre, Rovigo (Italy); Fuccio, Chiara [Fondazione Salvatore Maugeri, Service of Nuclear Medicine, Pavia (Italy)

    2013-02-15

    To determine the diagnostic efficacy of {sup 11}C-choline PET/CT in patients with prostate cancer (PC) after radical prostatectomy who presented with increasing PSA levels during follow-up in spite of being on hormone treatment (HT), and therefore showing HT resistance. We evaluated a large series of 157 consecutive PC patients previously treated by radical prostatectomy who presented with biochemical recurrence with increasing PSA levels in spite of ongoing HT (HT-resistant patients). At the time of {sup 11}C-choline PET/CT, the mean value of trigger PSA level was 8.3 (range 0.2 - 60.6 ng/mL), the mean PSA doubling time (PSAdt) was 5.3 (range 0.4 - 35 months), and the mean PSA velocity (PSAvel) was 22.1 ng/mL/year (range 0.12 - 82 ng/mL/year). {sup 11}C-Choline PET/CT was performed following a standard procedure at our centre to investigate increasing PSA levels, either as the first imaging procedure or in patients with negative conventional imaging. At the time of {sup 11}C-choline PET/CT all patients were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET-positive findings were validated by: (a) transrectal US-guided biopsy in patients with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c) other imaging modalities, including repeated {sup 11}C-choline PET/CT, performed during a minimum follow-up of 12-months. {sup 11}C-Choline PET/CT showed positive findings in 104 of the 157 patients (66 %). {sup 11}C-choline PET/CT detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7 patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes, 12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In {sup 11}C-choline PET-negative patients, the mean

  9. Weekly paclitaxel in escalating doses in a patient with anthracycline-resistant, triple-negative, metastatic breast cancer with severe liver dysfunction

    Directory of Open Access Journals (Sweden)

    Ajay Gupta

    2012-01-01

    Full Text Available Liver dysfunction in a patient with anthracycline-resistant breast cancer and liver metastases with poor performance status (PS represents a serious situation. Taxanes are the drugs of choice, but once the transaminase enzyme levels are raised more than 10-times the upper limit of normal (>10 ULN, paclitaxel administration is contraindicated. We present the report of one such case who had a gratifying response to escalating doses of weekly paclitaxel thus suggesting that even patients with severe liver dysfunction can derive benefits from such a strategy. The patient, a 54-year-old lady with breast cancer metastatic to the liver and bones and previous receipt of anthracycline-based therapy, presented to us with a PS of 3. Her liver functions (LFT were: serum bilirubin 2.2 mg% (0.3-1.1 mg%, aspartate aminotransferase 375 IU/L (0-25 IU/L, alanine aminotransferase 369 IU/L (0-35 IU/L and alkaline phosphatase 363 IU/L (38-126 IU/L. She was started on weekly paclitaxel 20 mg/m 2 and zoledronate. After the first dose, the LFTs rose marginally but the skin lesions stabilized. Dose was subsequently escalated to 40 mg/m 2 . At the end of the 10th week, her PS improved to 1 and the disease showed a partial response. LFTs improved markedly. However, 5 days after the administration of the 13 th dose, the disease progressed and paclitaxel had to be discontinued. It is possible to derive maximum palliative benefit with escalating doses of weekly paclitaxel even in patients whose liver functions are deranged with transaminase levels (>10 ULN and in whom conventional administration of paclitaxel is contraindicated.

  10. 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.

  11. {sup 18}F-fluoromethylcholine (FCH) PET imaging in patients with castration-resistant prostate cancer: prospective comparison with standard imaging

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, Michael; Siew, Teck [Royal Perth Hospital, Department of Nuclear Medicine, Perth, WA (Australia); WA PET Service, Sir Charles Gairdner Hospital, Perth, WA (Australia); Campbell, Andrew [Royal Perth Hospital, Department of Nuclear Medicine, Perth, WA (Australia); Royal Perth Hospital, Department of Medical Engineering and Physics, Perth, WA (Australia); Lenzo, Nat [WA PET Service, Sir Charles Gairdner Hospital, Perth, WA (Australia); Spry, Nigel [Sir Charles Gairdner Hospital, Department of Radiation Oncology, Perth, WA (Australia); University of Western Australia, Faculty of Medicine and Pharmacology, School of Medicine, Perth (Australia); Vivian, Justin [Royal Perth Hospital, School of Surgery, UWA, Perth (Australia); Morandeau, Laurence [Sir Charles Gairdner Hospital, Department of Medical Technology and Physics, Perth, WA (Australia)

    2011-01-15

    The aim of the study was to assess the utility of {sup 18}F-fluorocholine (FCH), compared to standard imaging of bone scan (BS) and contrast-enhanced abdominopelvic computed tomography (CT), in patients with castration-resistant prostate carcinoma. FCH has shown promise as a metabolic imaging agent for prostate carcinoma. Twenty-six patients with castration-resistant prostate carcinoma had FCH, BS and CT imaging within a 2-month period. Individual FCH-positive lesions in bone were compared to the BS and soft tissue lesions were compared to CT. The lesions were then classified as concordant or discordant for the presence or absence of prostate cancer metastases. Discordant bone or soft tissue lesions were followed up with BS or CT, respectively, at 6-month intervals for up to 2 years or until a definitive diagnosis of the discordant lesion could be made. In 13 (50%) of the patients, all lesions identified were concordant; this included 5 patients in whom no lesions could be identified with any imaging modality. In 21 patients, 183 lesions were observed with 149 being concordant and 34 (19%) being discordant (13 patients). Based on follow-up, FCH correctly identified the presence or absence of disease in 27 of 34 lesions, and in 14 cases FCH-positive lesions, not identified on initial imaging, were confirmed as disease on follow-up. The sensitivity, specificity, accuracy, positive predictive and negative predictive values for lesion detection by FCH are 96% (92-98%), 96% (81-99%), 96% (93-97%), 99% (96-100%) and 81% (64-88%), respectively, with 95% confidence intervals shown in parentheses. In this patient cohort, FCH shows good initial concordance (81%) with BS and CT in the detection of metastatic prostate carcinoma. Follow-up of the cases where FCH was initially discordant with subsequent BS or CT shows that FCH was accurate in determining the presence or absence of prostate metastasis in 79% of lesions. While FCH imaging as compared to BS and CT in this patient

  12. Rehabilitation of cancer patients.

    Directory of Open Access Journals (Sweden)

    Pandey M

    2001-01-01

    Full Text Available With the developments in cancer treatment, more and more patients are surviving their disease. However, very little emphasis is being placed to rehabilitate these cancer survivors. Ignorance, social structure, stigma attached in seeking psychological help, and poor communication skills of oncology staff all contribute to poor rehabilitative efforts. The priority of governmental agencies and health efforts to fight rampant communicable diseases, malnutrition, maternal health, and the frequent natural calamities, puts rehabilitation movements in the back seat. Treatment and prevention of disability and its rehabilitation requires comprehensive and multidisciplinary approach. There is an urgent need to promote physical and psychological rehabilitation.

  13. 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

    DEFF Research Database (Denmark)

    Christensen, Jesper F; Andersen, Jesper L; Adamsen, Lis

    2011-01-01

    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....... 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...

  14. Treatment of Hormone Resistance with Docetaxel in Metastatic Prostate Cancer Patients: Results of a Clinical Experience at Omid Hospital, Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Mina Tajvidi

    2017-01-01

    Full Text Available Background: Metastatic prostate cancer is one of the most important cancers among men worldwide. Androgen ablation therapy can be used in treatment of these patients; however, most will progress to metastatic hormone-refractory prostate cancer. In this regard, docetaxel has been approved to treat metastatic hormone-refractory prostate cancer in the United States. In this study, we aimed to investigate the results of this treatment modality in metastatic prostate cancer patients from Iran. Methods:We evaluated PSA response and bone pain relief in 18 metastatic prostate cancer patients who underwent treatment with docetaxel at a dose of 75 mg/m2 intravenously on the first day of treatment. The treatment was repeated every three weeks (6 cycles along with 10 mg of prednisolone. Results: Of 18 patients, 39% had >50% decline in PSA levels.There were 16% of the patients with a PSA decline of approximately 30% to 50% of the pre-treatment levels. In addition, 29% of the patients had progressive PSA levels during chemotherapy. Among them, 55% had significant pain relief. Conclusion: This research showed the effectiveness of docetaxel to decrease PSA levels in metastatic hormone-refractory prostate cancer patients from Iran. Docetaxel was also valuable in alleviation of pain in these patients. However, prospective studies should validate this approach.

  15. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  16. {sup 18}F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

    Energy Technology Data Exchange (ETDEWEB)

    De Giorgi, Ugo; Conteduca, Vincenza; Burgio, Salvatore Luca; Menna, Cecilia; Rossi, Lorena; Amadori, Dino [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy); Caroli, Paola; Paganelli, Giovanni; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Diagnostic Nuclear Medicine Unit, Meldola (Italy); Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [Morgagni-Pierantoni Hospital, Nuclear Medicine Unit, Forli (Italy)

    2015-07-15

    We investigated the role of {sup 18}F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response

  17. Drug resistance of deep fungi in cancer patients%肿瘤患者深部真菌耐药性分析

    Institute of Scientific and Technical Information of China (English)

    周杨霄; 蒋小伟; 李国钢; 李佳俊; 万汝根

    2012-01-01

    OBJECTIVE To understand the situation of drug resistance of the deep fungi in cancer patients, to provide evidence for rational use of antifungal agents. METHODS From Jun. 2006 to Jun. 2010, clinical specimens were cultured, and CHROMager Candida medium or ATB identification card were employed for strain identification. Susceptibility test was performed using the ATB-Fungus3 drug susceptibility plate. Retrospective and statistical analysis were performed. RESULTS Totally 386 strains of fungi were isolated. Detection rate was the highest in fungi isolated from the sputum, accounting for 47. 7% ; Candida albicans was the major pathogen in fungus infections, accounting for 58. 81% , followed by C. Glabrata, accounting for 17. 62%. The drug resistance rates to amphotericin B and-5-fluorocytosine were less than 10. 00% in isolated fungus, the resistance rates to fluconazole and itraconazol were higher. CONCLUSION Drug resistant strains of commonly used antifungal agents are increased in isolated fungus, the monitoring of drug resistance of fungi should be strengthened.%目的 了解肿瘤患者深部真菌的耐药现状,为临床合理使用抗真菌药物提供依据.方法 对2006年6月-2010年6月临床标本进行培养,用科玛嘉显色培养基或ATB鉴定卡作菌种鉴定,ATB-Fungus3药敏板进行药敏试验,并作回顾性分析和统计.结果 分离到真菌386株,在痰液中检出率最多,占47.7%;真菌感染中以白色假丝酵母菌为主,占58.81%,其次为光滑假丝酵母菌占17.62%;分离的菌株对两性霉素B和5-氟胞嘧啶的耐药率均<10.00%,对氟康唑和伊曲康唑的耐药率较高.结论 分离的菌株对常用抗真菌药物的耐药株增多,应加强对真菌耐药性的监测.

  18. FOXO factors and breast cancer: outfoxing endocrine resistance.

    Science.gov (United States)

    Bullock, M

    2016-02-01

    The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely common. Understanding the molecular pathways that regulate the hormone sensitivity of breast cancer cells is important to improving the efficacy of endocrine therapy. It is becoming clearer that the PI3K-AKT-forkhead box O (FOXO) signaling axis is a key player in the hormone-independent growth of many breast cancers. Constitutive PI3K-AKT pathway activation, a driver of breast cancer growth, causes down-regulation of FOXO tumor suppressor functions. This review will summarize what is currently known about the role of FOXOs in endocrine-resistance mechanisms. It will also suggest potential therapeutic strategies for the restoration of normal FOXO transcriptional activity.

  19. Venous thromboembolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Mehmet Fuat Eren

    2013-09-01

    Full Text Available Venous thromboembolism (VTE is a major complication of cancer and represents an important cause of morbidity and mortality. The incidence of VTE is 0.6-7.8% in patients with cancer more than double the incidence of VTE in patients without cancer. The risk of VTE which includes deep venous thrombosis (DVT and pulmonary embolism (PE is increased two to seven fold in patients with cancer. VTE risk is especially high among certain groups such as hospitalized patients with cancer and those receiving active antineoplastic therapy. Also cancer patients, who undergoing major surgery, are increased risk of VTE. Trauma, long-haul travel, increased age, obesity, previous VTE and genetic component are also predisposing factors for VTE. Patients with cancer who develop VTE should be managed multidisciplinary treatment guidelines. The primary goal of thromboprophylaxis in patients with cancer is to prevent VTE. The large majority of cancer patients should be treated with therapeutic doses of unfractioned heparin (UFH or low molecular weight heparin (LMWH. Prophylaxis should include cancer patients who underwent major surgery for cancer and patients with a history of VTE.

  20. Cancer patients' evaluation of communication

    DEFF Research Database (Denmark)

    Ross, Lone; Petersen, Morten Aagaard; Johnsen, Anna Thit;

    2013-01-01

    The aims of this study were to assess how communication with health care staff is perceived by Danish cancer patients and to characterise those patients who report problems in communication.......The aims of this study were to assess how communication with health care staff is perceived by Danish cancer patients and to characterise those patients who report problems in communication....

  1. Lung cancer in younger patients

    DEFF Research Database (Denmark)

    Abbasowa, Leda; Madsen, Poul Henning

    2016-01-01

    INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age...... differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly...... diagnosed lung cancer patients were included. RESULTS: Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours...

  2. Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer

    DEFF Research Database (Denmark)

    Mathers, John C; Movahedi, Mohammad; Macrae, Finlay;

    2012-01-01

    , for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly...... assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990. FINDINGS: 463 patients were randomly assigned to receive resistant starch and 455 to receive resistant-starch placebo. At a median follow-up 52...

  3. [Colorectal cancer in spouses of colorectal cancer patients].

    Science.gov (United States)

    Matsumata, T; Shikada, Y; Hasuda, S; Kishihara, F; Suehiro, T; Funahashi, S; Nagamatsu, Y; Iso, Y; Shima, I; Koga, C; Osamura, S; Ueda, M; Furuya, K; Sakino, I

    2000-06-01

    Married couples share home environments and life style for years. In the case of colorectal cancer, an association with insulin resistance was reported. We determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84 colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of the distal colorectal cancer, which has been declining in the United States, was significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p = 0.0400). Some mechanisms may promote the progression of mucosal lesions to invasive cancers in the distal colorectum. There were no significant differences with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs 22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84 couples in whom colorectal cancer develops at least in one may then not illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no lean...". The spouses had been married for an average of 38 years, and in 30 spouses who had been followed in a colorectal cancer screening, 5 developed colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we might advise screening colonoscopy to the spouses of colorectal cancer patients, or déjà vu all over again?

  4. Pain in patients with cancer

    NARCIS (Netherlands)

    Vissers, K.C.P.; Besse, K.; Wagemans, M.; Zuurmond, W.; Giezeman, M.J.; Lataster, A.; Mekhail, N.; Burton, A.W.; Kleef, M. van; Huygen, F.

    2011-01-01

    Pain in patients with cancer can be refractory to pharmacological treatment or intolerable side effects of pharmacological treatment may seriously disturb patients' quality of life. Specific interventional pain management techniques can be an effective alternative for those patients. The appropriate

  5. Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

    Science.gov (United States)

    Verzoni, Elena; Giorgi, Ugo De; Derosa, Lisa; Caffo, Orazio; Boccardo, Francesco; Facchini, Gaetano; Porcu, Luca; Vincenzo, Fabio De; Zaniboni, Alberto; Chiuri, Vincenzo Emanuele; Fratino, Lucia; Santini, Daniele; Adamo, Vincenzo; Vivo, Rocco De; Dinota, Angelo; Messina, Caterina; Ricotta, Riccardo; Caserta, Claudia; Scavelli, Claudio; Susi, Marina; Tartarone, Alfredo; Surace, Giuseppe; Mosca, Alessandra; Bruno, Michele; Barni, Sandro; Grassi, Paolo; Procopio, Giuseppe

    2016-01-01

    We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies. PMID:27223078

  6. The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

    Science.gov (United States)

    Boegemann, Martin; Schlack, Katrin; Thomes, Stefan; Steinestel, Julie; Rahbar, Kambiz; Semjonow, Axel; Schrader, Andres Jan; Aringer, Martin; Krabbe, Laura-Maria

    2017-01-01

    The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR 5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9–2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0–1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3–4.0); p 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to 5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully. PMID:28208664

  7. Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.

    Science.gov (United States)

    Adams, Scott C; Segal, Roanne J; McKenzie, Donald C; Vallerand, James R; Morielli, Andria R; Mackey, John R; Gelmon, Karen; Friedenreich, Christine M; Reid, Robert D; Courneya, Kerry S

    2016-08-01

    The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL.

  8. Antimicrobial Resistance Pattern and Their Beta-Lactamase Encoding Genes among Pseudomonas aeruginosa Strains Isolated from Cancer Patients

    Directory of Open Access Journals (Sweden)

    Mai M. Zafer

    2014-01-01

    Full Text Available This study was designed to investigate the prevalence of metallo-β-lactamases (MBL and extended-spectrum β-lactamases (ESBL in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of blaVIM-2, blaOXA-10-, blaVEB-1, blaNDM-, and blaIMP-1-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, blaVIM-2- and blaOXA-10-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of blaVIM-2, blaIMP-1, blaNDM, and blaOXA-10 in P. aeruginosa in Egypt.

  9. 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

    2013-01-01

    -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...

  10. Illuminating Cancer Resistance in Elephants.

    Science.gov (United States)

    2015-12-01

    A new study shows that elephants have at least 20 copies of the tumor suppressor gene TP53; their cells also favor apoptosis over DNA repair when subjected to DNA-damaging agents. These findings may help explain elephants' longevity and low cancer risk, and shed further light on natural cancer suppression mechanisms.

  11. 'Patient satisfaction' in hospitalized cancer patients.

    Science.gov (United States)

    Skarstein, Jon; Dahl, Alv A; Laading, Jacob; Fosså, Sophie D

    2002-01-01

    Predictors of 'patient satisfaction' with hospitalization at a specialized cancer hospital in Norway are examined in this study. Two weeks after their last hospitalization, 2021 consecutive cancer patients were invited to rate their satisfaction with hospitalization, quality of life, anxiety and depression. Compliance rate was 72% (n = 1453). Cut-off levels separating dissatisfied from satisfied patients were defined. It was found that 92% of the patients were satisfied with their stay in hospital, independent of cancer type and number of previous admissions. Performance of nurses and physicians, level of information perceived, outcome of health status, reception at the hospital and anxiety independently predicted 'patient satisfaction'. The model explained 35% of the variance with an area under the curve of 0.76 of the Receiver Operator Curve. Cancer patients' satisfaction with their hospital stay was high, and predicted by four independently predictive variables related to the performance of caregivers. These suggest areas for further improvement in the healthcare service.

  12. Palliative care in castrate-resistant prostate cancer.

    Science.gov (United States)

    Rabow, Michael W; Lee, Michael Xiang

    2012-11-01

    Significant symptoms and suffering related to castrate-resistant prostate cancer (CRPC) are associated with the disease and its treatment. Increasingly, with advances in treatment efficacy, men can live with symptoms for long periods. Interdisciplinary palliative care teams (including physicians, nurses, social workers, chaplains, pharmacists, psychologists, physical therapists, and nutritionists) focused on symptom management and patients' goals of care can collaborate with prostate cancer surgeons, oncologists, and radiation oncologists to provide the best care for men at all stages of treatment, including end of life. This article reviews the benefits of palliative care in helping patients with CRPC manage symptoms and distress.

  13. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

    2007-01-01

    for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...... with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance...

  14. Cancer Exosomes as Mediators of Drug Resistance.

    Science.gov (United States)

    André, Maria do Rosário; Pedro, Ana; Lyden, David

    2016-01-01

    In the last decades, several studies demonstrated that the tumor microenvironment is a critical determinant not only of tumor progression and metastasis, but also of resistance to therapy. Exosomes are small membrane vesicles of endocytic origin, which contain mRNAs, DNA fragments, and proteins, and are released by many different cell types, including cancer cells. Mounting evidence has shown that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with the tumor microenvironment. Understanding how exosomes and the tumor microenvironment impact drug resistance will allow novel and better strategies to overcome drug resistance and treat cancer. Here, we describe a technique for exosome purification from cell culture, and fresh and frozen plasma, and further analysis by electron microscopy, NanoSight microscope, and Western blot.

  15. Management of patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Gillessen, S; Omlin, A; Attard, G

    2015-01-01

    -resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion......The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration...... decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged....

  16. Trastuzumab: updated mechanisms of action and resistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Francois X. Claret

    2012-06-01

    Full Text Available HER2-postitive breast cancer has the second-poorest prognosis among breast cancer subtypes. One of the most effective targeted therapies for patients with HER2-positive breast cancer is trastuzumab-based. However, primary or acquired resistance to trastuzumab has been a major obstacle in the clinical management of this disease. Therefore, to better control HER2-postitive breast cancer, it is necessary to gain a deeper understanding of trastuzumab’s actions and the pathways that cancer cells use to dodge its effects. In this review, we attempt to give an overview of the widely accepted and currently proposed molecular mechanisms for these actions and highlight recent advances in our understanding of HER2 targeted therapies.

  17. TCRP1 contributes to cisplatin resistance by preventing Pol β degradation in lung cancer cells.

    Science.gov (United States)

    Liu, Xiaorong; Wang, Chengkun; Gu, Yixue; Zhang, Zhijie; Zheng, Guopei; He, Zhimin

    2015-01-01

    Cisplatin (DDP) is the first-line chemotherapy drug widely used for the treatment of lung cancer patients, whereas the majority of cancer patients will eventually show resistance to DDP. The mechanisms responsible for DDP resistance are not fully understood. Tongue cancer resistance-associated protein 1 (TCRP1) gene was recently cloned and reported to specially mediate DDP resistance in human oral squamous cell carcinoma (OSCC) cells. However, the mechanisms of TCRP1-mediated DDP resistance are far from clear, and whether TCRP1 participates in DDP resistance in lung cancer cells remains unknown. Here, we show that TCRP1 contributes to DDP resistance in lung cancer cells. Knockdown of TCRP1 sensitizes the cells to DDP and increases the DDP-induced DNA damage. We have identified that Pol β is associated with DDP resistance, and Pol β knockdown delays the repair of DDP-induced DNA damage in A549/DDP cells. We find TCRP1 interacts with Pol β in lung cancer cells. Moreover, TCRP1 knockdown decreases the level of Pol β and increases the level of its ubiquitination. These results suggest that TCRP1 contributes to DDP resistance through the prevention of Pol β degradation in lung cancer cells. These findings provide new insights into chemoresistance and may contribute to prevention and reversal of DDP resistance in treatment of lung cancer in the future.

  18. Association Between Insulin Resistance and Luminal B Subtype Breast Cancer in Postmenopausal Women.

    Science.gov (United States)

    Nam, Sanggeun; Park, Seho; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Kim, Seung Il

    2016-03-01

    Currently, there is limited information on the clinical characteristics of breast cancer patients with insulin resistance. Hence, the purpose of this study was to investigate the association between insulin resistance and clinicopathological factors in newly diagnosed breast cancer patients without diabetes. We assessed 760 patients with breast cancer treated between 2012 and 2014. We compared the clinicopathological characteristics between patients with and without insulin resistance using univariate and multivariate analyses, including after stratification by menopausal status. Insulin resistance was defined according to the homeostatic model assessment of insulin resistance. Of 760 patients, 26.4% had insulin resistance. Age, menopausal status, body mass index, tumor size, histologic grade, Ki-67 expression, and breast cancer subtype significantly differed according to the presence of insulin resistance. Multivariate analysis revealed that postmenopausal status and obesity were significantly associated with insulin resistance. In postmenopausal women, older age, obesity, larger tumor size, advanced stage, and high proliferative luminal B subtype were significantly associated with insulin resistance. In contrast, in premenopausal patients, only obesity was related to insulin resistance. Multivariate analysis indicated that insulin resistance was independently correlated with obesity, larger tumor size, and the luminal B/human epidermal growth factor receptor-2-negative subtype in postmenopausal but not premenopausal patients. Insulin resistance was significantly associated with larger tumors and proliferative luminal B subtype breast cancer in postmenopausal women only. These findings suggest that insulin resistance could mechanistically induce tumor progression and might be a good prognostic factor, and that it could represent a therapeutic target in postmenopausal patients with breast cancer.

  19. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer

    DEFF Research Database (Denmark)

    Idorn, Manja; Køllgaard, Tania; Kongsted, Per

    2014-01-01

    and function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies...... and other cell types may suggest ways to tackle their induction and/or function to improve immunological tumor control....

  20. Multidrug-resistant breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Martin HL

    2014-01-01

    Full Text Available Heather L Martin,1 Laura Smith,2 Darren C Tomlinson11BioScreening Technology Group, Leeds Institutes of Molecular Medicine, University of Leeds, Leeds, UK; 2Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UKAbstract: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. By understanding the molecular mechanisms behind multidrug-resistant breast cancer, new treatments may be developed. Here we review the recent advances in this understanding, emphasizing the common mechanisms underlying resistance to both targeted therapies, notably tamoxifen and trastuzumab, and traditional chemotherapies. We focus primarily on three molecular mechanisms, the phosphatidylinositide 3-kinase/Akt pathway, the role of microRNAs in gene silencing, and epigenetic alterations affecting gene expression, and discuss how these mechanisms can interact in multidrug resistance. The development of therapeutics targeting these mechanisms is also addressed.Keywords: PI3K/Akt, epigenetics, miRNA, ER, HER2, triple negative

  1. 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

    records from 421 consecutive patients treated with first-line docetaxel (75 mg/m(2) every 3 weeks) and low-dose prednisolone from 2007 to 2013 at Herlev University Hospital were reviewed. Common Terminology Criteria for Adverse Events, version 4.0, and the Prostate Cancer Working Group 2 guidelines were...

  2. The Placorhen study : A double-blind, placebo-controlled, randomized radionuclide study with Re-186-etidronate in hormone-resistant prostate cancer patients with painful bone metastases

    NARCIS (Netherlands)

    Han, SH; de Klerk, JMH; Tan, S; van het Schip, AD; Derksen, BH; van Dijk, A; Kruitwagen, CLJJ; Blijham, GH; van Rijk, PP; Zonnenberg, BA

    2002-01-01

    Re-186-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using Re-186-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain. Methods: Pain relief was assessed us

  3. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Andersen, J L

    2014-01-01

    implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle......, be powered to evaluate clinical outcomes associated with improvements in muscle function, or be promoted in advanced stage settings, aiming to reverse cancer-related muscle dysfunction, and thus potentially improve time-to-progression, treatment toxicity and survival....

  4. Castration-Resistant Prostate Cancer: Mechanisms, Targets, and Treatment

    Directory of Open Access Journals (Sweden)

    Teresa Maria Santos Amaral

    2012-01-01

    Full Text Available Patients with castration-resistant prostate cancer (CRPC, who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC.

  5. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib

    DEFF Research Database (Denmark)

    Sorensen, Boe S; Wu, Lin; Wei, Wen;

    2014-01-01

    BACKGROUND: The feasibility of monitoring epidermal growth factor receptor (EGFR) mutations in plasma DNA from patients with advanced non-small cell lung cancer (NSCLC) during treatment with erlotinib and its relation to disease progression was investigated. METHODS: The amount of EGFR-mutant DNA...... was tested in plasma DNA from patients with advanced NSCLC with allele-specific polymerase chain reaction assays. Blood samples from 23 patients with adenocarcinoma of NSCLC that carried tyrosine kinase inhibitor-sensitizing EGFR mutations were taken immediately before treatment with erlotinib. Additional...... blood samples were taken at timed intervals until erlotinib treatment was withdrawn. RESULTS: The amount of plasma DNA with sensitizing EGFR mutations was found to be reduced after the first cycle of erlotinib treatment in 22 of 23 patients (96%). No patients presented with the resistant T790M mutation...

  6. 肿瘤患者感染病原菌的分布及耐药性分析%The distribution and drug resistance of pathogens specttum in cancer patients during hospitalization

    Institute of Scientific and Technical Information of China (English)

    慕玉东; 楚雍烈; 王永兴

    2011-01-01

    目的:了解肿瘤患者感染病原菌的分布及耐药性分析,为合理用药提供依据.方法:对本院肿瘤患者送检的合格标本分离菌株进行培养鉴定和耐药性分析.结果: 405株病原菌中G- 杆菌228株,占56.3%;G+球菌67株,占16.5%;真菌110株,占27.2%;药敏试验结果提示G-杆菌对亚胺培南、美罗培南高度敏感,对氨苄西林、哌拉西林耐药率很高.结论:肿瘤患者易发生院内感染且易产生耐药株,在选择抗生素时应依据药敏实验结果合理选用药物,控制病原菌的耐药性.%Objective :To study the distribution and drug resistance of pathogens spectrum in cancer patients and provide the basis of rational use of medecines. Methods ; Qualified samples of cancer patients in our hospital were cultered isolated identification and analyzed drug resistance. Results : Of 405 pathogens spectrum the G - bacilli were 228 ( 56. 3 % ) , and C+ coccis were 67 ( 16. 5% ) , and fungi were 110( 27. 2% ) . The results of susceptibility test suggested : the G- bacilli had a highly senstive to imipenem and meropenem, and had a highly resiatant againat ampicillin ang piperacillin. Conclusions : Cancer patients prone to nosoconual infection with resistant strains easily, so the selection of antibiotics should be based on the results of sensitivity tests, to control drug resistance.

  7. 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

    for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited from treatment with enzalutamide...... in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged falls. CLINICAL TRIAL IDENTIFIER: NCT01212991, ClinicalTrials.gov.......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...

  8. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification

    DEFF Research Database (Denmark)

    Tarpgaard, Line S.; Qvortrup, Camilla; Nygård, Sune Boris

    2016-01-01

    UNLABELLED: ᅟ: The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2......A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin...... in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6 % of these tumors had TOP2A copy gain and 2.0 % had loss of TOP2A when compared to adjacent...

  9. Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer

    DEFF Research Database (Denmark)

    Larsen, Sarah L; Yde, Christina W; Laenkholm, Anne-Vibeke

    2015-01-01

    treatment targets. METHODS: Antiestrogen sensitive and resistant T47D breast cancer cell lines were used as model systems. Parental and fulvestrant resistant cell lines were subjected to a kinase inhibitor library. Kinase inhibitors preferentially targeting growth of fulvestrant resistant cells were...... for endocrine resistance, immunohistochemistry was performed on archival primary tumor tissue from breast cancer patients who have received adjuvant endocrine treatment with tamoxifen. RESULTS: The selective Aurora kinase B inhibitor barasertib was identified to preferentially inhibit growth of fulvestrant...... resistant T47D breast cancer cell lines. Compared with parental cells, phosphorylation of Aurora kinase B was higher in the fulvestrant resistant T47D cells. Barasertib induced degradation of Aurora kinase B, caused mitotic errors, and induced apoptotic cell death as measured by accumulation of SubG1 cells...

  10. BCAR4 induces antioestrogen resistance but sensitises breast cancer to lapatinib

    NARCIS (Netherlands)

    M.F.E. Godinho (Marcia F.E.); J.D. Wulfkuhle (Julia D.); M.P. Look (Maxime); A.M. Sieuwerts (Anieta); S. Sleijfer (Stefan); J.A. Foekens (John); E.F. Petricoin (Emanuel F.); L.C.J. Dorssers (Lambert); T.L.A. van Agthoven (Thecla)

    2012-01-01

    textabstractBackground: High BCAR4 and ERBB2 mRNA levels in primary breast cancer associate with tamoxifen resistance and poor patient outcome. We determined whether BCAR4 expression sensitises breast cancer cells to lapatinib, and identifies a subgroup of patients who possibly may benefit from ERBB

  11. Cancer resistance as an acquired and inheritable trait

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

    2014-01-01

    AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer...... cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype...... was named HICR (heritable induced cancer resistance) and was defined as primary resistant progeny from mice immunized with frozen/thawed or irradiated S180 cells or CFAF obtained from mice with S180 induced ascites. Notably, this resistance was transferred from both male and female mice to the offspring...

  12. Pulmonary embolism in cancer patients

    Directory of Open Access Journals (Sweden)

    S P Sawant

    2012-01-01

    Full Text Available Aims and Objectives: Pulmonary embolism (PE is rare in the Indian population and is under-reported in patients with malignancy. We studied the clinical profile and outcome of patients with PE and cancer in the Indian population. Materials and Methods: Data of cancer patients with PE, admitted in a tertiary cancer centre, was analyzed. The prevalence of PE was calculated as the number of patients with PE per 10,000 hospital admissions. The demographic data, details of cancer, co-morbidities, details of PE, and treatment given for PE and their outcomes were recorded and analyzed. Results: There were 56,425 hospital admissions in the study period. The prevalence of PE was 6.4 per 10,000 hospital admissions .Thirty-six cancer patients were diagnosed to have PE. In females, gynecological malignancies (36.84% and in males gastrointestinal, head and neck cancers, and hematological malignancies were the most common sites (17.7% each. PE was associated with DVT in 41.7%. Dyspnea was the most common presenting symptom. Five patients (13.88% were asymptomatic and were incidentally detected to have PE . The most common echocardiographic finding was right ventricular dysfunction (55.55%. Mortality among the treated patients was 22% (7 / 31 and in untreated patients it was 80% (4 / 5. The factors that had an impact on a three-month survival were, the presence of massive PE (P = 0.019 and the presence of RV dysfunction at presentation (P = 0.005. Conclusion: The prevalence of PE and mortality due to PE is high in cancer patients. Risk stratification for venous thromboembolism (VTE should be done in all cancer patients and thromboprophylaxis should be optimally used.

  13. Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: A meta-analysis of published trials.

    Science.gov (United States)

    Roviello, Giandomenico; Sigala, Sandra; Danesi, Romano; Re, Marzia Del; Bonetta, Alberto; Cappelletti, Maria Rosa; Zanotti, Laura; Bottini, Alberto; Generali, Daniele

    2016-05-01

    Abiraterone acetate and orteronel are two CYP-17 inhibitors that have been studied in prostate cancer. They have shown relevant toxicities, including fluid retention/oedema, hypokalaemia, hypertension, liver function test abnormalities and cardiac events. The goal of this study was to determine the risk of special adverse events related to CYP- 17 inhibitor in patients with metastatic castration-resistant prostate cancer (CRCP). Summary data from four randomized phase III trials comparing CYP-17 inhibitors and prednisone versus placebo and prednisone in metastatic CRCP patients were meta-analysed. Pooled risk ratios (RRs) for the risk of all-grade and grade 3-4 adverse events of special interest were calculated. Data from 4916 patients (2849 in the AA experimental arm; 2067 in the control arm) were analysed. The incidence of grade 3-4 adverse events was never more than 10% of the patients. However, compared with placebo, the CYP-17 inhibitor significantly increased the all-grade events of hypertension (RR=1.53; 95% CI=1.3-1.8; pevents, hypokalaemia (RR=4.23; 95% CI=1.28-13.99; p=0.02) and cardiac disorders (RR=1.55; 95% CI=1.18-2.05; p=0.002). A lot of adverse events such as hypertension, hypokalaemia, cardiac disorders and liver function test abnormalities are increased during CYP-17 inhibitor based therapy. Strict monitoring of these side effects should be considered during CYP- 17 inhibitor therapy in prostate cancer patients.

  14. Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Alsner, Jan; Rødningen, Olaug K.; Overgaard, Jens

    2007-01-01

    -induced changes in gene expression in fibroblasts, whether differential expression is more pronounced when looking at the fold induction levels, taking into account the differences in background expression levels between patients, and whether there is a linear correlation between individual risk of RIF...... and changes in radiation-induced gene expression in fibroblasts. MATERIAL AND METHODS: Gene expression was analysed by quantitative real-time PCR before and after a fractionated scheme with 3x3.5Gy/3 days in fibroblasts derived from 26 patients with breast cancer treated with post-mastectomy radiotherapy....... RESULTS: Robust radiation-induced changes in gene expression were observed, with differential gene expression between low and high risk patients being most pronounced for the fold induction level ('after' value divided by 'before' value for each patient). When including patients with intermediate risk...

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

    Directory of Open Access Journals (Sweden)

    Fidia Mumtahana

    2014-12-01

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

  16. Urotherapy for patients with cancer.

    Science.gov (United States)

    Eldor, J

    1997-04-01

    Cancer cells release various antigens, some of which appear in the urine. Oral autourotherapy is suggested as a new treatment modality for cancer patients. It will provide the intestinal lymphatic system with the many tumor antigens against which antibodies may be produced. These antibodies may be pierced through the blood stream and attack the tumor and its cells.

  17. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced...... cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...

  18. Perioperative nutrition in cancer patients.

    Science.gov (United States)

    Daly, J M; Redmond, H P; Gallagher, H

    1992-01-01

    Cancer patients have the highest incidence of protein-calorie malnutrition seen in hospitalized patients, with significant malnutrition occurring in more than 30% of cancer patients undergoing major upper gastrointestinal procedures. Clinically significant malnutrition occurs as a result of diminished nutrient intake, increased nutrient losses, and tumor-induced derangements in host metabolism. In the absence of adequate exogenous nutrients, the body utilizes endogenous substrates to satisfy the ongoing requirements of both host and tumor for energy and protein. In those patients with malignant obstruction of the gastrointestinal tract, the tumor itself may induce diminished nutrient intake. Present day treatment modalities including gastrointestinal resection, chemotherapy, and radiotherapy compound these metabolic derangements, further increasing the risk of postoperative morbidity and death. The presence of malnutrition in cancer patients has prognostic importance. In a review of more than 3000 cancer patients, DeWys and colleagues identified significantly improved survival in those patients without weight loss compared with those had lost 6% of their body weight (Am J Med 69:491-497, 1980). Other investigators have noted increased postoperative morbidity and mortality associated with malnutrition. Early hypotheses suggested that reversal of weight loss would improve survival. The development and refinements of enteral and parenteral nutrition have provided the opportunity for studying the relationship between nutritional supplementation and postoperative prognosis. Nutrition support is therefore often instituted to improve nutritional status and thereby reduce the risks of postoperative complications. This article addresses the beneficial role of preoperative nutrition therapy in cancer patients.

  19. Patient-reported Measurements of Oral Mucositis in Head and Neck Cancer Patients Treated With Radiotherapy With or Without Chemotherapy Demonstration of Increased Frequency, Severity, Resistance to Palliation, and Impact on Quality of Life

    NARCIS (Netherlands)

    Elting, Linda S.; Keefe, Dorothy M.; Sonis, Stephen T.; Garden, Adam S.; Spijkervet, F. K. L.; Barasch, Andrei; Tishler, Roy B.; Canty, Thomas P.; Kudrimoti, Mahesh K.; Vera-Lionch, Montserrat

    2008-01-01

    BACKGROUND. I-lie risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated. METHODS. A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illne

  20. Cancer

    Science.gov (United States)

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

  1. Resistance to cancer in amphibians: a role for apoptosis?

    Science.gov (United States)

    Ruben, Laurens N; Johnson, Rachel O; Clothier, Richard H; Balls, Michael

    2013-07-01

    The rarity of spontaneous cancer in amphibians, and the difficulty of inducing cancer in these lower vertebrates, suggest that they possess an effective system for resistance to the development of cancer. The first part of this narrative presents evidence for cancer resistance in amphibians, and then a variety of studies designed to help understand the physiological basis for this resistance are reviewed. Here, our emphasis is on evidence with regard to the role that apoptosis might play.

  2. Characterisation and Manipulation of Docetaxel Resistant Prostate Cancer Cell Lines

    LENUS (Irish Health Repository)

    O'Neill, Amanda J

    2011-10-07

    Abstract Background There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. Results The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. Conclusion This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.

  3. Cancer Screening in Older Patients.

    Science.gov (United States)

    Salzman, Brooke; Beldowski, Kathryn; de la Paz, Amanda

    2016-04-15

    Although cancer is the second leading cause of death among persons 65 years and older, there is a paucity of clinical trial data about the effectiveness and harms of cancer screening in this population. Given the heterogeneous nature of the older population, cancer screening in these patients should not be based on age alone. Studies suggest that a life expectancy of at least 10 years is necessary to derive a survival benefit from screening for breast and colorectal cancers; therefore, screening for these cancers is not recommended in those with a life expectancy of less than 10 years. Prostate cancer screening, if performed at all, should not be performed after 69 years of age. Cervical cancer screening may be stopped after 65 years of age if the patient has an adequate history of negative screening results. An individualized approach to cancer screening decisions involves estimating life expectancy, determining the potential benefits and harms of screenings, and weighing those benefits and harms in relation to the patient's values and preferences.

  4. Feasibility and efficacy of progressive resistance training and dietary supplements in radiotherapy treated head and neck cancer patients - the DAHANCA 25A study

    DEFF Research Database (Denmark)

    Lønbro, Simon; Dalgas, Ulrik; Primdahl, Hanne

    2013-01-01

    ) increases muscle mass among healthy individuals and groups of cancer patients, but it has not been investigated in HNSCC patients. Furthermore, studies in healthy subjects show an additive effect of protein and creatine supplementation following PRT. Objectives. Firstly, to investigate the feasibility of 12...... weeks of PRT ± protein and creatine supplementation among HNSCC patients. Secondly, to investigate group changes over time and group differences regarding lean body mass (LBM), muscle strength and functional performance following PRT ± dietary supplementation. Material and methods. Thirty patients were...... randomized into two groups: a PROCR group undergoing a seven-day pre-trial creatine loading protocol followed by 12 weeks of PRT with creatine and protein supplementation and a PLA group undergoing a seven-day pre-trial placebo ingestion protocol followed by an identical PRT protocol with placebo...

  5. FAU regulates carboplatin resistance in ovarian cancer.

    Science.gov (United States)

    Moss, Esther L; Mourtada-Maarabouni, Mirna; Pickard, Mark R; Redman, Charles W; Williams, Gwyn T

    2010-01-01

    The development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short-interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin-induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal-Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin-induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P FAU was examined by quantitative real-time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal-Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum-resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer.

  6. The new concepts on overcoming drug resistance in lung cancer

    Directory of Open Access Journals (Sweden)

    Zhang W

    2014-06-01

    Full Text Available Weisan Zhang,1 Ping Lei,1 Xifeng Dong,2 Cuiping Xu31Department of Geriatrics, 2Department of Hematology-Oncology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Qianfoshan Hospital, Shandong University, Jinan, People’s Republic of ChinaAbstract: Lung cancer is one of the most deadly diseases worldwide. The current first-line therapies include chemotherapy using epidermal growth factor receptor tyrosine kinase inhibitors and radiotherapies. With the current progress in identifying new molecular targets, acquired drug resistance stands as an obstacle for good prognosis. About half the patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor treatments develop resistance. Although extensive studies have been applied to elucidate the underlying mechanisms, evidence is far from enough to establish a well-defined picture to correct resistance. In the review, we will discuss four different currently developed strategies that have the potential to overcome drug resistance in lung cancer therapies and facilitate prolonged anticancer effects of the first-line therapies.Keywords: ALK receptors cancer stem cell, chemotherapy, EGFR-TKI, target therapy, pharmacology, molecular biology, biotherapy

  7. Psychological aspects of cancer patients

    Directory of Open Access Journals (Sweden)

    Graça Cardoso

    2014-06-01

    Full Text Available Cancer is accompanied by important psychological distress experienced by both patient and family. From the moment of the diagnosis on, the patient has to develop a great number of mechanisms and tasks of adjustment to the illness and its circumstances. The high prevalence of anxiety and depressive disorders during the course of cancer increases in the end stage disea‐ se. Therefore, a global plan of intervention integrating somatic and psychological/ psychiatric care throughout all the phases of the illness is crucial in the treatment of these patients. Health professionals working on this field can also experience emotional reactions to their patients’ suffering. They should be aware of the emotional aspects involved and develop training to help them intervene adequately with the patient and the family. The articulation between oncologists, palliative care professionals, and mental health care teams can be of great help in providing good quality of care to cancer patients.

  8. Plasma AR and abiraterone-resistant prostate cancer.

    Science.gov (United States)

    Romanel, Alessandro; Gasi Tandefelt, Delila; Conteduca, Vincenza; Jayaram, Anuradha; Casiraghi, Nicola; Wetterskog, Daniel; Salvi, Samanta; Amadori, Dino; Zafeiriou, Zafeiris; Rescigno, Pasquale; Bianchini, Diletta; Gurioli, Giorgia; Casadio, Valentina; Carreira, Suzanne; Goodall, Jane; Wingate, Anna; Ferraldeschi, Roberta; Tunariu, Nina; Flohr, Penny; De Giorgi, Ugo; de Bono, Johann S; Demichelis, Francesca; Attard, Gerhardt

    2015-11-01

    Androgen receptor (AR) gene aberrations are rare in prostate cancer before primary hormone treatment but emerge with castration resistance. To determine AR gene status using a minimally invasive assay that could have broad clinical utility, we developed a targeted next-generation sequencing approach amenable to plasma DNA, covering all AR coding bases and genomic regions that are highly informative in prostate cancer. We sequenced 274 plasma samples from 97 castration-resistant prostate cancer patients treated with abiraterone at two institutions. We controlled for normal DNA in patients' circulation and detected a sufficiently high tumor DNA fraction to quantify AR copy number state in 217 samples (80 patients). Detection of AR copy number gain and point mutations in plasma were inversely correlated, supported further by the enrichment of nonsynonymous versus synonymous mutations in AR copy number normal as opposed to AR gain samples. Whereas AR copy number was unchanged from before treatment to progression and no mutant AR alleles showed signal for acquired gain, we observed emergence of T878A or L702H AR amino acid changes in 13% of tumors at progression on abiraterone. Patients with AR gain or T878A or L702H before abiraterone (45%) were 4.9 and 7.8 times less likely to have a ≥50 or ≥90% decline in prostate-specific antigen (PSA), respectively, and had a significantly worse overall [hazard ratio (HR), 7.33; 95% confidence interval (CI), 3.51 to 15.34; P = 1.3 × 10(-9)) and progression-free (HR, 3.73; 95% CI, 2.17 to 6.41; P = 5.6 × 10(-7)) survival. Evaluation of plasma AR by next-generation sequencing could identify cancers with primary resistance to abiraterone.

  9. 130例肺癌患者肺部感染病原菌与耐药性分析%Pathogen and drug resistance analysis of 130 cases of lung cancer patients complicated with pulmonary infec-tion

    Institute of Scientific and Technical Information of China (English)

    曾茄

    2016-01-01

    Objective To analyze the pathogen and drug resistance of lung cancer patients complicated with pulmonary infection. Methods The sputum specimens of 130 lung cancer patients complicated with pulmonary in-fection were given pathogenic bacteria culture and drug sensitive test, and the results were analyzed. Results There were a total of 221 strains of pathogenic bacteria isolated, mainly including gram-negative bacteria (59. 73%). Path-ogenic bacteria showed different degree of resistance to all kinds of antibacterial drugs, and there existed multiple drug resistance. Conclusion The main pathogen of lung cancer patients complicated with lung infection is gram-neg-ative bacteria, and it shows serious drug resistance and multiple drug resistance. Etiology examination and drug re-sistance monitoring should be strengthened to provide the basis for clinical rational use of antibiotics.%目的:探讨肺癌患者肺部感染病原菌分布与耐药特点,为临床抗菌药物的使用提供依据。方法将我院130例肺癌合并肺部感染住院患者的痰标本进行病原菌培养与药敏试验,对结果进行统计分析。结果送检标本中共分离出221株病原菌,以革兰阴性菌为主,占59.73%;病原菌对各种抗菌药物存在不同程度的耐药性,存在多重耐药性。结论肺癌患者肺部感染病原菌主要为革兰阴性菌,耐药现象严重,且具有多重耐药性。加强对肺癌患者肺部感染病原学检查与耐药监测可为临床合理使用抗生素提供依据。

  10. Progressive resistance training rebuilds lean body mass in head and neck cancer patients after radiotherapy - Results from the randomized DAHANCA 25B trial

    DEFF Research Database (Denmark)

    Lønbro, Simon; Dalgas, Ulrik; Primdahl, Hanne;

    2013-01-01

    PURPOSE: The critical weight loss observed in head and neck squamous cell carcinoma (HNSCC) patients following radiotherapy is mainly due to loss of lean body mass. This is associated with decreases in muscle strength, functional performance and Quality of Life (QoL). The present study investigated...... the effect of progressive resistance training (PRT) on lean body mass, muscle strength and functional performance in HNSCC patients following radiotherapy. PATIENTS AND METHODS: Following radiotherapy HNSCC patients were randomized into two groups: Early Exercise (EE, n=20) initiated 12weeks of PRT followed...... by 12weeks of self-chosen physical activity. Delayed Exercise (DE, n=21) initiated 12weeks of self-chosen physical activity followed by 12weeks of PRT. Lean body mass, muscle strength, functional performance and QoL were evaluated at baseline and after week 12 and 24. RESULTS: In the first 12weeks lean...

  11. 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.

  12. MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells.

    Science.gov (United States)

    Fessler, Shawn P; Wotkowicz, Mark T; Mahanta, Sanjeev K; Bamdad, Cynthia

    2009-11-01

    In the United States, 211,000 women are diagnosed each year with breast cancer. Of the 42,000 breast cancer patients who overexpress the HER2 growth factor receptor, Herceptin). Despite those statistics, women diagnosed with breast cancer are now tested to determine how much of this important growth factor receptor is present in their tumor because patients whose treatment includes trastuzumab are three-times more likely to survive for at least 5 years and are two-times more likely to survive without a cancer recurrence. Unfortunately, even among the group whose cancers originally respond to trastuzumab, 25% of the metastatic breast cancer patients acquire resistance to trastuzumab within the first year of treatment. Follow-on "salvage" therapies have prolonged life for this group but have not been curative. Thus, it is critically important to understand the mechanisms of trastuzumab resistance and develop therapies that reverse or prevent it. Here, we report that molecular analysis of a cancer cell line that was induced to acquire trastuzumab resistance showed a dramatic increase in the amount of the cleaved form of the MUC1 protein, called MUC1*. We recently reported that MUC1* functions as a growth factor receptor on cancer cells and on embryonic stem cells. Here, we show that treating trastuzumab-resistant cancer cells with a combination of MUC1* antagonists and trastuzumab, reverses the drug resistance. Further, HER2-positive cancer cells that are intrinsically resistant to trastuzumab became trastuzumab-sensitive when treated with MUC1* antagonists and trastuzumab. Additionally, we found that tumor cells that had acquired Herceptin resistance had also acquired resistance to standard chemotherapy agents like Taxol, Doxorubicin, and Cyclophosphamide. Acquired resistance to these standard chemotherapy drugs was also reversed by combined treatment with the original drug plus a MUC1* inhibitor.

  13. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida

    2016-01-01

    Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...... resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired...

  14. Prostate Cancer Stem-like Cells Contribute to the Development of Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Diane Ojo

    2015-11-01

    Full Text Available Androgen deprivation therapy (ADT has been the standard care for patients with advanced prostate cancer (PC since the 1940s. Although ADT shows clear benefits for many patients, castration-resistant prostate cancer (CRPC inevitably occurs. In fact, with the two recent FDA-approved second-generation anti-androgens abiraterone and enzalutamide, resistance develops rapidly in patients with CRPC, despite their initial effectiveness. The lack of effective therapeutic solutions towards CRPC largely reflects our limited understanding of the underlying mechanisms responsible for CRPC development. While persistent androgen receptor (AR signaling under castration levels of serum testosterone (<50 ng/mL contributes to resistance to ADT, it is also clear that CRPC evolves via complex mechanisms. Nevertheless, the physiological impact of individual mechanisms and whether these mechanisms function in a cohesive manner in promoting CRPC are elusive. In spite of these uncertainties, emerging evidence supports a critical role of prostate cancer stem-like cells (PCSLCs in stimulating CRPC evolution and resistance to abiraterone and enzalutamide. In this review, we will discuss the recent evidence supporting the involvement of PCSLC in CRPC acquisition as well as the pathways and factors contributing to PCSLC expansion in response to ADT.

  15. The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms.

    Science.gov (United States)

    Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F; Winter, Jordan M; Brody, Jonathan R

    2016-01-01

    Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.

  16. 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.

    2013-01-01

    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 pr

  17. Detecting and treating breast cancer resistance to EGFR inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Moonlee, Sun-Young; Bissell, Mina J.; Furuta, Saori; Meier, Roland; Kenny, Paraic A.

    2016-04-05

    The application describes therapeutic compositions and methods for treating cancer. For example, therapeutic compositions and methods related to inhibition of FAM83A (family with sequence similarity 83) are provided. The application also describes methods for diagnosing cancer resistance to EGFR inhibitors. For example, a method of diagnosing cancer resistance to EGFR inhibitors by detecting increased FAM83A levels is described.

  18. STROBE-compliant integrin through focal adhesion involve in cancer stem cell and multidrug resistance of ovarian cancer

    Science.gov (United States)

    Wei, Luwei; Yin, Fuqiang; Zhang, Wei; Li, Li

    2017-01-01

    Abstract Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer. A total of 36 ovarian CSC genes involved in regulation of drug resistance were summarized, and potential drug resistance-related CSC genes were identified based on 3 independent microarrays retrieved from the Gene Expression Omnibus (GEO) Profiles. Pathway enrichment of CSC genes associated with drug resistance in ovarian cancer indicated that focal adhesion signaling might play important roles in CSC genes-mediated drug resistance. Integrins are members of the adhesion molecules family, and integrin subunit alpha 1, integrin subunit alpha 5, and integrin subunit alpha 6 (ITGA6) were identified as central CSC genes and their expression in side population cells, cisplatin-resistant SKOV3 (SKOV3/DDP2) cells, and cisplatin-resistant A2780 (A2780/DDP) cells were dysregulated as measured by real-time quantitative polymerase chain reaction. The high expression of ITGA6 in 287 ovarian cancer patients of TCGA cohort was significantly associated with poorer progression-free survival. This study provide the basis for further understanding of CSC genes in regulation of drug resistance in ovarian cancer, and integrins could be a potential biomarker for prognosis of ovarian cancer. PMID:28328815

  19. [Trastuzumab (Herceptin) and breast cancer: mechanisms of resistance].

    Science.gov (United States)

    Dieras, Véronique; Vincent-Salomon, Anne; Degeorges, Armelle; Beuzeboc, Philippe; Mignot, Laurent; de Cremoux, Patricia

    2007-03-01

    The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. The mechanism of trastuzumab action is not fully understood but has been related to cell cycle inhibition. As to mechanisms of resistance, little is known but many preclinical data raised different hypothesis. Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.

  20. p53 protein aggregation promotes platinum resistance in ovarian cancer.

    Science.gov (United States)

    Yang-Hartwich, Y; Soteras, M G; Lin, Z P; Holmberg, J; Sumi, N; Craveiro, V; Liang, M; Romanoff, E; Bingham, J; Garofalo, F; Alvero, A; Mor, G

    2015-07-01

    High-grade serous ovarian carcinoma (HGSOC), the most lethal gynecological cancer, often leads to chemoresistant diseases. The p53 protein is a key transcriptional factor regulating cellular homeostasis. A majority of HGSOCs have inactive p53 because of genetic mutations. However, genetic mutation is not the only cause of p53 inactivation. The aggregation of p53 protein has been discovered in different types of cancers and may be responsible for impairing the normal transcriptional activation and pro-apoptotic functions of p53. We demonstrated that in a unique population of HGSOC cancer cells with cancer stem cell properties, p53 protein aggregation is associated with p53 inactivation and platinum resistance. When these cancer stem cells differentiated into their chemosensitive progeny, they lost tumor-initiating capacity and p53 aggregates. In addition to the association of p53 aggregation and chemoresistance in HGSOC cells, we further demonstrated that the overexpression of a p53-positive regulator, p14ARF, inhibited MDM2-mediated p53 degradation and led to the imbalance of p53 turnover that promoted the formation of p53 aggregates. With in vitro and in vivo models, we demonstrated that the inhibition of p14ARF could suppress p53 aggregation and sensitize cancer cells to platinum treatment. Moreover, by two-dimensional gel electrophoresis and mass spectrometry we discovered that the aggregated p53 may function uniquely by interacting with proteins that are critical for cancer cell survival and tumor progression. Our findings help us understand the poor chemoresponse of a subset of HGSOC patients and suggest p53 aggregation as a new marker for chemoresistance. Our findings also suggest that inhibiting p53 aggregation can reactivate p53 pro-apoptotic function. Therefore, p53 aggregation is a potential therapeutic target for reversing chemoresistance. This is paramount for improving ovarian cancer patients' responses to chemotherapy, and thus increasing their

  1. Resistance to apoptosis should not be taken as a hallmark of cancer

    Institute of Scientific and Technical Information of China (English)

    Rui-An Wang; Zeng-Shan Li; Qing-Guo Yan; Xiu-Wu Bian; Yan-Qing Ding; Xiang Du; Bao-Cun Sun; Yun-Tian Sun; Xiang-Hong Zhang

    2014-01-01

    In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usualy observed simultaneously in cancerous lesions. Studies have shown that increased apoptosis is associated with cancer aggressiveness and poor clinical outcome. Furthermore, overexpression of Bcl-2, an antiapoptotic protein, is linked with better survival of cancer patients. Conversely, Bax, CD95, Caspase-3, and other apoptosis-inducing proteins have been found to promote carcinogenesis. This notion of the role of apoptosis in cancer is not new; cancer cells were found to be short-lived 88 years ago. Given these observations, resistance to apoptosis should not be considered a halmark of cancer.

  2. Mechanisms of multidrug resistance in cancer.

    Science.gov (United States)

    Gillet, Jean-Pierre; Gottesman, Michael M

    2010-01-01

    The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.

  3. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ömer Acar

    2013-01-01

    Full Text Available The effective treatment of castrate-resistant prostate cancer (CRPC has proven to be very challenging. Until recently, docetaxel was the only therapeutic demonstrated to extend overall patient survival. Yet recently, a considerable number of new therapeutics have been approved to treat CRPC patients. These remarkable advances now give new tools for the therapeutic management of late-stage prostate cancer. In this review, we will examine mechanistic and clinical data of several newly approved therapeutics including the chemotherapeutic cabazitaxel, antiandrogen enzalutamide, endocrine disruptor abiraterone acetate, immunotherapy sipuleucel-T, and bone-targeting radiopharmaceutical alpharadin. In addition, we will examine other promising therapeutics that are currently in Phase III trials.

  4. Evolutionary strategy for systemic therapy of metastatic breast cancer: balancing response with suppression of resistance.

    Science.gov (United States)

    Kam, Yoonseok; Das, Tuhin; Minton, Susan; Gatenby, Robert A

    2014-07-01

    Conventional systemic therapy for disseminated breast cancer is based on the general assumption that the greatest patient benefit is achieved by killing the maximum number of tumor cells. While this strategy often achieves a significant reduction in tumor burden, most patients with metastatic breast cancer ultimately die from their disease as therapy fails because tumor cells evolve resistance. We propose that the conventional maximum dose/maximum cell kill cancer therapy, when viewed from an evolutionary vantage, is suboptimal and likely even harmful as it accelerates evolution and growth of the resistant phenotypes that ultimately cause patient death. As an alternative, we are investigating evolutionary therapeutic strategies that shift the treatment goal from killing the maximum number of cancer cells to maximizing patient survival. Here we introduce two novel approaches for systemic therapy for metastatic breast cancer, considering the evolutionary nature of tumor progression; adaptive therapy and double-bind therapy.

  5. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Storgaard, Heidi; Holst, Jens J;

    2015-01-01

    BACKGROUND: Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies...... no differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp. LIMITATIONS: The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production. CONCLUSION: Patients with psoriasis were more insulin resistant compared...

  6. Salinomycin induces apoptosis in cisplatin-resistant colorectal cancer cells by accumulation of reactive oxygen species.

    Science.gov (United States)

    Zhou, Jin; Li, Pu; Xue, Xiaofeng; He, Songbing; Kuang, Yuting; Zhao, Hong; Chen, Shaoji; Zhi, Qiaoming; Guo, Xiaobo

    2013-10-24

    Postoperative chemotherapy for Colorectal cancer (CRC) patients is not all effective and the main reason might lie in cancer stem cells (CSCs). Emerging studies showed that CSCs overexpress some drug-resistance related proteins, which efficiently transport the chemotherapeutics out of cancer cells. Salinomycin, which considered as a novel and an effective anticancer drug, is found to have the ability to kill both CSCs and therapy-resistant cancer cells. To explore the potential mechanisms that salinomycin could specifically target on therapy-resistant cancer cells in colorectal cancers, we firstly obtained cisplatin-resistant (Cisp-resistant) SW620 cells by repeated exposure to 5 μmol/l of cisplatin from an original colorectal cancer cell line. These Cisp-resistant SW620 cells, which maintained a relative quiescent state (G0/G1 arrest) and displayed stem-like signatures (up-regulations of Sox2, Oct4, Nanog, Klf4, Hes1, CD24, CD26, CD44, CD133, CD166, Lgr5, ALDH1A1 and ALDH1A3 mRNA expressions) (p 0.05), but could induce cell death process (p GSH-PX activities (p cisplatin-resistant colorectal cancer cells.

  7. Thromboembolism in Patients with Cancer.

    Science.gov (United States)

    Büyükçelik, Abdullah; Akbulut, Hakan

    2004-03-01

    One hundred and forty years ago, Armand Trousseau described phlegmasia alba dolens as a sign of internal malignancy. Nowadays, it is commonly believed that the presence malignant tumaor increases the risk of venous thromboembolism (i.e deep vein thrombosis and pulmonary embolism) However, cancer is usually associated with other factors such as old age, extensive surgery,immobility, etc., which may predispose to thromboembolism. The majority of thrombotic events occur in the venous system; the incidence of arterial thrombosis is much lower.Recurrent thromboembolism in cancer patients frequently and diminishes the quality of life of the patients.Furthermore, if the thromboembolism is massive, destipte of early and aggressive treatment, it may result in death. In this article, we review thromboembolic complications in cancer patients.

  8. Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

    Science.gov (United States)

    García-Becerra, Rocío; Santos, Nancy; Díaz, Lorenza; Camacho, Javier

    2013-01-01

    Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. PMID:23344024

  9. Hypertension in Patients with Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade, E-mail: wolney@cardiol.br [Curso de Pós-Graduação em Ciências Cardiovasculares da Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2015-03-15

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

  10. Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer.

    LENUS (Irish Health Repository)

    Mohd Sharial, M S N

    2012-12-01

    Approximately 15%-23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed.

  11. Novel agents in the management of castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Shruti Chaturvedi

    2014-01-01

    Full Text Available Prostate cancer (PCa is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC. Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.

  12. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida;

    2016-01-01

    highly prioritized by the applied network-based gene ranking approach. At higher docetaxel concentration MCF-7 subclones exhibited a copy number loss in E2F4, and the gene encoding this important transcription factor was down-regulated in MCF-7 resistant cells. Conclusions: Our study of the evolution......Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...

  13. [Weight loss in cancer patients].

    Science.gov (United States)

    Lordick, Florian; Hacker, Ulrich

    2016-02-01

    Cancer patients are regularly affected by malnutrition which often leads to a worsened quality of life and activity in daily living, more side effects and complications during anticancer treatment and shorter survival times. The early diagnosis and treatment of malnutrition are therefore relevant components of oncological treatment. The assessment of the nutritional status and determination of the body-mass-index should be done in every patient with cancer. The clinical examination delivers important findings and indications for malnutrition. Bioimpedance analysis can deliver additional objective information. The treatment of malnutrition should start early and follows a step-wise escalation reaching from nutritional counseling to enteral nutritional support to parenteral nutrition.

  14. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5

    NARCIS (Netherlands)

    K. Fizazi (Karim); R. Jones (Robert); S. Oudard (Stéphane); E. Efstathiou (Eleni); F. Saad (Fred); R. de Wit (Ronald); J.S. de Bono (Johann); F.M. Cruz (Felipe Melo); G. Fountzilas (George); A. Ulys (Albertas); F. Carcano (Flavio); N. Agarwal (Neeraj); D. Agus (David); J. Bellmunt (Joaquim); D.P. Petrylak (Daniel P); S.-Y. Lee (Shih-Yuan); I.J. Webb (Iain J.); B. Tejura (Bindu); N. Borgstein (Niels); R. Dreicer (Robert)

    2015-01-01

    textabstractPurpose: Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods: In our study, 1,099

  15. 恶性肿瘤患者医院感染病原菌及耐药特征分析%Distribution and drug resistance of pathogens in cancer patients with nosocomiai infection

    Institute of Scientific and Technical Information of China (English)

    阮燕萍; 张文英; 毛彩萍; 王明丽

    2009-01-01

    目的 了解恶性肿瘤患者医院感染的病原菌分布及其耐药特征.方法 对浙江省肿瘤医院2004-2008年恶性肿瘤患者医院感染的病原菌及耐药情况进行统计分析.结果 共检出病原菌3454株,其中革兰阴性菌1900株,占55.0%,真菌838株,占24.3%,革兰阳性菌716株,占20.7%.主要病原菌是大肠埃希菌和白假丝酵母菌,主要通过手术切口、泌尿道、呼吸道和口腔等引起感染.革兰阴性菌中的大肠埃希菌和革兰阳性菌中的葡萄球菌耐药率高,真菌中的白假丝酵母菌对各种抗真菌药物均较敏感.结论 恶性肿瘤患者医院感染的病原菌以条件致病菌为主,部分细菌对抗菌药物的耐药情况相当严重.%Objective To investigate the distribution and drug resistance of pathogens in cancer patients with nosocomial infections. Methods Pathogens isolated from cancer patients with nosocomial infections in Zhejiang Cancer Hospital from 2004 to 2008 were analyzed. Results Totally 3454 strains of pathogens were isolated, including 1900 strains of Gram-negative bacilli (55.0%), 838 strains of fungi (24.3%), and 716 strains of Gram-positive bacteria (20.7%). Pathogenic bacteria Escherichia coli and Candida albicans were isolated mainly from surgical wound, urinary tract, respiratory tract and oral cavity. The drug resistant rates for Gram-negative Escherichia coli and Gram-positive staphylococci were high, and Candida albicans was sensitive to all antifungal drugs. Conclusion Opportunistic pathogens account for most nosocomial infections in cancer patients, and some of them are of high-level resistance to antimicrobial agents.

  16. Patient Beliefs About Colon Cancer Screening.

    Science.gov (United States)

    Ely, John W; Levy, Barcey T; Daly, Jeanette; Xu, Yinghui

    2016-03-01

    Only about half of eligible individuals undergo colon cancer screening. We have limited knowledge about the patient beliefs that adversely affect screening decisions and about which beliefs might be amenable to change through education. As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported their beliefs about colon cancer screening in response to a mailed questionnaire. Consenting subjects were randomized into four groups, which were distinguished by four levels of increasingly intensive efforts to promote screening. Two of the groups received mailed educational materials and completed a follow-up questionnaire, which allowed us to determine whether their beliefs about screening changed following the education. We also completed a factor analysis to identify underlying (latent) factors that might explain the responses to 33 questions about readiness, attitudes, and perceived barriers related to colon cancer screening. The strongest predictors of a patient's stated readiness to be screened were a physician's recommendation to be screened (1 point difference on 10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point difference), a family history of colon cancer (0.85-point Likert scale difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should be mostly left to physicians rather than patients (Spearman correlation coefficient 0.21, P beliefs, 11 (33 %) changed favorably following the educational intervention. In the factor analysis, the 33 items were reduced to 8 underlying factors, such as being too busy to undergo screening and worries about screening procedures. We found a limited number of underlying factors that may help explain patient resistance to colon cancer screening.

  17. What Do Prostate Cancer Patients Die Of?

    OpenAIRE

    Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

    2011-01-01

    The cause of death in prostate cancer patients is examined using the Swedish Family-Cancer Database. Prostate cancer patients were found to have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure.

  18. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

  19. Pegfilgrastim in pediatric cancer patients

    NARCIS (Netherlands)

    te Poele, EM; Kamps, WA; Tamminga, RYJ; Leew, JA; Postma, A; de Bont, ESJM

    2005-01-01

    Chemotherapy-induced neutropenia is a major dose-limiting side effect of intensive chemotherapy in cancer patients. Recently, pegfilgrastim (a product with a long half-life, resulting in once-per-cycle dosage) was introduced to prevent neutropenia in adults. The authors report 32 episodes of pegfilg

  20. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J.E.; Brennan, M.T.; Verdonck- de Leeuw, I.M.; Gibson, R.J.; Eilers, J.G.; Waltimo, T.; Bots, C.P.; Michelet, M.; Sollecito, T.P.; Rouleau, T.S.; Sewnaik, A.; Bensadoun, R.J.; Fliedner, M.C.; Silverman, S.; Spijkervet, F.K.L.

    2012-01-01

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalen

  1. Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells.

    Science.gov (United States)

    Carpin, Laura B; Bickford, Lissett R; Agollah, Germaine; Yu, Tse-Kuan; Schiff, Rachel; Li, Yi; Drezek, Rebekah A

    2011-01-01

    Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specificity of the nanoshells for HER2+ breast cancer. Silica-gold nanoshells conjugated with anti-HER2 were incubated with both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells. Nanoshell binding was confirmed using two-photon laser scanning microscopy, and the cells were then ablated using a near-infrared laser. We demonstrate the successful targeting and ablation of trastuzumab-resistant cells using anti-HER2-conjugated silica-gold nanoshells and a near-infrared laser. This study suggests potential for applying gold nanoshell-mediated therapy to trastuzumab-resistant breast cancers in vivo.

  2. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer

    Science.gov (United States)

    Tsai, Hsiang-Ping; An, Herng-Wei; Lee, Chi-Ming; Wu, Jen-Chine; Chen, Chien-Shu; Huang, Shih-Hao; Hwang, Jaulang; Cheng, Kur-Ta; Leiw, Phui-Ly; Chen, Chi-Long; Lin, Chun-Mao

    2015-01-01

    DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers. PMID:26207989

  3. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Lee

    Full Text Available DNA topoisomerase I (TOP1 levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT resistance in ovarian cancers and identified evodiamine (EVO, a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024. EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01 in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

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

    Directory of Open Access Journals (Sweden)

    McClung EC

    2016-03-01

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

  5. Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways

    OpenAIRE

    Liu, Enling; Liu, Zheng; Zhou, Yuxiu; Mi, Ruoran; Wang, Dehua

    2015-01-01

    Ovarian cancer is the most lethal gynecologic malignancy. Cisplatin is a very effective cancer chemotherapy drug, but cisplatin resistance is a crucial problem of therapy failure. Overexpression of PVT1 has been demonstrated in ovarian cancer. The mRNA level of PVT1 in ovarian cancer tissues of cisplatin-resistant patients and cisplatin-sensitive patients, cisplatin-resistant cells SKOV-3/DDP and A2780/DDP, cisplatin-sensitive cells SKOV-3 and A2780 were determined by qRT-PCR. The influence o...

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Nafees Ahmad

    2016-02-01

    Full Text Available Abstract Background Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. Objective To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. Methods This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients’ socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. Results High degree of drug resistance (median 5 drugs, range 2–8 was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%, and more than half were resistant to second line drugs (55.1%. The majority of the patients were ofloxacin resistant (52.7%. Upon multivariate analysis previous tuberculosis treatment at private (OR = 1.953, p = 0.034 and public private mix (OR = 2.824, p = 0.046 sectors were predictors of ofloxacin resistance. Conclusion The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public–private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

  8. 肺癌患者并发肺部感染的病原菌谱及耐药基因检测%Pathogens causing pulmonary infections in lung cancer patients and drug resistance genes

    Institute of Scientific and Technical Information of China (English)

    崔艳慧; 梁海军; 杨留中; 张清琴; 花勤亮

    2012-01-01

    目的 了解肺癌患者合并肺部感染的病原菌谱及主要病原菌的耐药基因,以指导临床合理应用抗菌药物.方法 对220例肺癌并发肺部感染患者进行痰培养,其中100例培养阳性,对培养阳性的细菌进行鉴定;应用纸片扩散法对主要细菌进行药敏试验,并应用PCR法检测主要细菌的耐药基因.结果 肺癌并肺部感染的病原菌以革兰阴性菌为主占62.0%、革兰阳性菌占31.0%,真菌占7.0%,革兰阴性菌以大肠埃希菌、肺炎克雷伯菌及铜绿假单胞菌为主,革兰阳性菌以金黄色葡萄球菌及肺炎链球菌为主,革兰阴性菌及阳性菌对多种抗菌药物耐药;部分大肠埃希菌及肺炎克雷伯菌携带TEM型及SHV型耐药基因.结论 肺癌并肺部感染以革兰阴性菌最为常见,多药耐药严重,部分携带有耐药基因.%OBJECTIVE To explore the spectrum of the pathogens causing pulmonary infections in lung cancer patients as well as the drug resistant genes ir the main pathogens so as to guide tie reaso nable use of antibiotics. METHODS The sputum culture was performed for 220 lung cancer patients combined with pulmonary infections, among which there were 100 cases cultured positive, then the bacteria isolated from the positive cases were identified; the drug susceptibility testing for the main pathogens was carried out by using disk diffusion method, the drug resistance genes in the main bacteria were detected with PCR. RESULTS The main pathogens involving in the pulmonary infections combined with lung cancer were as follows : gram—negative bacteria (62.0%), gram-positive bacteria (31. 0%) ,and fungi (7. 0%) , the predominant gram-negative bacilli included Escherichia coli , Kleb-siella pneumoniae and Pseudomonas aeruginosa , the predominant gram-positive bacteria were Staphylococcus au-reus and Streptococcs pneumoniae ; the gram-negative bacteria and gram-positive bacteria were resistant to many antibiotics; part of E. coli

  9. Variation of Protein's Expression Correlated to the Drug Resistance after Sequential Anti-cancer Treatment in Human Lung Cancer Cell Line

    Institute of Scientific and Technical Information of China (English)

    Zhi-hong Chi; Ji-ren Zhang; Peng Li; Duan-qi Liu

    2005-01-01

    @@ Multi-drug resistance is one of the leading causes for fai lure to treat patients with cancer. This study is to explore the expression of the proteins correlated with chemoresistance in a human lung cancer cell line (LPET-a-1) repeatedly treated by anti-cancer drugs.

  10. A Role for Notch Signalling in Breast Cancer and Endocrine Resistance

    Directory of Open Access Journals (Sweden)

    Ahmet Acar

    2016-01-01

    Full Text Available Over the past decade, there has been growing interest in the Notch signalling pathway within the breast cancer field. This interest stemmed initially from the observation that Notch signalling is aberrantly activated in breast cancer and its effects on various cellular processes including proliferation, apoptosis, and cancer stem cell activity. However more recently, elevated Notch signalling has been correlated with therapy resistance in oestrogen receptor-positive breast cancer. As a result, inhibiting Notch signalling with therapeutic agents is being explored as a promising treatment option for breast cancer patients.

  11. Chronic diseases among older cancer patients.

    NARCIS (Netherlands)

    Deckx, L.D.; Akker, M.A. van der; Metsemakers, J.M.; Knottnerus, A.K.; Schellevis, F.G.; Buntinx, F.B.

    2011-01-01

    Introduction: With the growing number of older cancer patients, the burden of chronic diseases among older cancer patients will become increasingly important. Chronic diseases often interfere with treatment decisions and prognosis for cancer patients. However, little is known about the occurrence of

  12. Pain and Distress in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Anna Burger-Szabo

    2015-09-01

    Full Text Available Background: A significant number of patients with cancer suffer from anxiety and depressive disorder. Perceived emotional distress, anxiety and depressive symptoms are significantly more frequent in cancer patients with pain than in patients without pain. Despite their high prevalence cancer pain and distress are frequently undertreated.

  13. Analysis of drug resistance and pathogenic bacteria in lung cancer patients with lower respiratory tract infection%肺恶性肿瘤患者下呼吸道感染的病原菌及耐药性分析

    Institute of Scientific and Technical Information of China (English)

    李剑

    2011-01-01

    目的 探讨肺恶性肿瘤患者呼吸道感染病原菌分布及抗菌素的耐药情况。方法 回顾分析2006年5月至2009年5月286例住院肺恶性肿瘤患者下呼吸道感染的病原菌以及耐药性的检测结果。结果 下呼吸道感染的病原菌主要为革兰阴性杆菌(50.70%),其中铜绿假单菌比重最高(18.18%),大肠埃希菌第二(13.64%),肺炎克雷伯菌第三(11.19%),革兰阳性(G+)球菌占20.28%,真菌高达29.02%。病原菌对常用抗菌药物有很高的耐药性,革兰阴性杆菌对亚安培南的敏感性最高,其次是头孢哌酮、环丙沙星、阿米卡星。革兰阳性球菌敏感性最高为万古霉素。结论 肺恶性肿瘤患者合并下呼吸道感染要及时做病原菌及耐药性分析,合理应用抗生素,降低耐药菌对恶性肿瘤患者的危害。%Objective To investigate respiratory tract infection pathogens in patients with lung cancer and antibiotic resistance of the distribution. Methods Retrospective analysis of our hospital in May 2006 ~ May 2009 totally 286 cases of lung cancer patients hospitalized with lower respiratory tract infection pathogens and drug resistance testing, the results were analyzed. Results Lower respiratory tract infection pathogens mainly Gram - negative bacilli (50. 70% ) , of which the highest proportion of Pseudomonas aeruginosa bacteria (18. 18% ), Escherichia coli Ⅱ(13. 64% ), Klebsiella pneumoniae third (11.19%), Gram - positive (G + ) cocci accounted for 20. 28% , fungi up to 29. 02%. Pathogens to commonly used antibiotics has a high resistance of Gram - negative bacilli sensitive to Imipen-em, followed by cefoperazone, ciprofloxacin, amikacin. Gram - positive cocci highest susceptibility to vancomycin. Conclusions Lung cancer patients with lower respiratory tract infection pathogens and drug resistance in time to do analysis, rational use of antibiotics to reduce the harm resistant to the cancer patients.

  14. 宫颈癌患者术后感染病原菌及耐药性分析%Pathogens causing postoperative infections in cervical cancer patients and analysis of drug resistance

    Institute of Scientific and Technical Information of China (English)

    俞晶; 杨宏英; 朱娇阳; 向旭东

    2013-01-01

    目的 了解宫颈癌患者术后感染病原菌及对常用抗菌药物的耐药性,为临床治疗宫颈癌时合理用药提供参考.方法 以2009年1月—2012年8月在医院进行宫颈癌手术并发生术后感染的113例患者为研究对象,取患者宫颈分泌物进行细菌培养和鉴定,采用纸片法(K-B法)进行药敏试验.结果 1678例宫颈癌手术患者发生术后感染113例,感染率为6.73%,感染部位以手术切口为主,占49.35%,其次为泌尿道和盆腔,分别占23.38%和20.12%;113例宫颈癌术后感染患者共分离出1 54株病原菌,以革兰阴性菌为主占63.64%;其次为革兰阳性菌和真菌,分别占29.87%和6.49%;革兰阴性菌中大肠埃希菌对氨苄西林和哌拉西林的耐药率较高,为97.67%及93.02%,肺炎克雷伯菌对氨苄西林和哌拉西林的耐药率为85.00%和75.00%,铜绿假单胞菌对阿米卡星的耐药率最高为70.59%,主要革兰阴性菌对头孢吡肟、亚胺培南较敏感,耐药率<33.00%.结论 宫颈癌患者术后感染病原菌种类复杂,细菌耐药性较强,临床治疗时应该根据药敏试验结果合理选择抗菌药物,并动态监测其耐药性变化.%OBJECTIVE To understand the pathogens causing postoperative infections in cervical cancer patients and analyze the drug resistance to commonly used antibiotics so as to guide the reasonable medication for the clinical treatment of cervical cancer.METHODS A total of 113 cervical cancer patients who underwent cervical cancer surgery in the hospital from Jan 2009 to Aug 2012 were enrolled in the study,then the cervical secretions were sampled for the bacterial culture and identification,and the drug susceptibility testing was performed by K-B method.RESULTS Of totally 1678 cases of cervical cancer surgery patients,the postoperative infections occurred in 113 cases with the incidence rate of 6.73 %;the patients with surgical incision infections accounted for 49.35

  15. A changing landscape in castration resistant prostate cancer treatment

    Directory of Open Access Journals (Sweden)

    Alessandra eFelici

    2012-07-01

    Full Text Available Prostate cancer (PC is the leading cause of cancer and the second leading cause of cancer-death among men in the Western world. About 10%-20% of men with PC present with metastatic disease at diagnosis, while 20%-30% of patients diagnosed with localized disease will eventually develop metastases. Although most respond to initial androgen deprivation therapy (ADT, progression to castration resistant PC (CRPC is universal. In 2004 the docetaxel/prednisone regimen was approved for the management of patients with metastatic CRPC, becoming the standard first-line therapy. Recent advances have now led to an unprecedented number of new drug approvals within the past years, providing many new treatment options for patients with metastatic CRPC. Four new drugs have received U.S. Food and Drug Administration (FDA-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. The data supporting the approval of each of these agents are described in this review, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies.

  16. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida;

    2016-01-01

    highly prioritized by the applied network-based gene ranking approach. At higher docetaxel concentration MCF-7 subclones exhibited a copy number loss in E2F4, and the gene encoding this important transcription factor was down-regulated in MCF-7 resistant cells. Conclusions: Our study of the evolution...... of acquired docetaxel resistance identified several genomic changes that might explain development of docetaxel resistance. Interestingly, the most relevant resistance-associated changes appeared to originate midway through the evolution towards fully resistant cell lines. Our data suggest that no single......Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...

  17. Emerging concepts on drug resistance in bladder cancer: Implications for future strategies.

    Science.gov (United States)

    Massari, Francesco; Santoni, Matteo; Ciccarese, Chiara; Brunelli, Matteo; Conti, Alessandro; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Tortora, Giampaolo

    2015-10-01

    The combination chemotherapies with methotrexate plus vinblastine, doxorubicin and cisplatin (MVAC or CMV regimens) or gemcitabine plus cisplatin represent the standard as first-line therapy for patients with metastatic urothelial cancer. In Europe, vinflunine is an option for second-line therapy for patients progressed during first-line or perioperative platinum-containing regimen. Alternative regimens containing taxanes and/or gemcitabine may be valuated case by case. Furthermore, carboplatin should be considered in patients unfit for cisplatin both in the first and second-line setting. Based on these findings, a better comprehension of the mechanisms underlying the development of drug resistance in patients with bladder cancer will represent a major step forward in optimizing patients' outcome. This article reviews the current knowledge of the mechanisms and emerging strategies to overcome resistance in patients with advanced urothelial cancer.

  18. Preliminary research on dendritic cells loaded with resistant breast cancer antigens in breast cancer-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Wei Zhuang; Limin Lun

    2015-01-01

    Objective The aim of the study was to investigate the inhibitory ef ects of dendritic cel s (DCs) loaded with resistant breast cancer antigens on breast cancer in nude mice. Methods A single-cel suspension was prepared from a primary breast cancer and chemotherapeutic drugs were screened using the ATP-PCA susceptibility testing system. Cancer cel s were treated with 1/10 × IC50, 1/5 × IC50, 1/2 × IC50, 1 × IC50, and 2 × IC50 medium until their growth became steady in the 2 × IC50 medium. Peripheral blood mononuclear cel s (PBMCs) were obtained from the peripheral blood of patients with leukapheresis. The obtained adherent cel s were induced by granulocyte-macrophage colony-stimu-lating factor (GM-CSF) and interleukin-4 (IL-4) to generate DCs, which carried resistant strain cel lysis compounds or non-treated cancer cel lysis compounds. The former mature DCs carried resistant breast tumor antigens. A breast tumor-bearing nude mouse model was established with these resistant strains and the mice were randomly divided in three groups. The mice in the treatment group were injected with DCs loaded with resistant breast cancer antigens. The control group consisted of mice injected with DCs loaded with primary tumor cel antigens and the blank group consisted of mice injected with the same volume of normal saline. Changes in the cancers were observed. Results After treatment with the ef ector cel s, the cancer volume and weight were significantly dif erent to those before treatment in every group of mice (P Conclusion DCs loaded with resistant breast cancer antigens demonstrated a significant inhibition ef ect on the cancers of breast tumor-bearing nude mice.

  19. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification

    DEFF Research Database (Denmark)

    Tarpgaard, Line S.; Qvortrup, Camilla; Nygård, Sune Boris;

    2016-01-01

    A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin...... normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5 % had a ratio ≥ 1.5 consistent with gene amplification and 2.6 % had a ratio ≤ 0.8 suggesting gene deletions. Based on these observations......, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio ≥ 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon's two-stage minimax...

  20. Association of ERCC1 protein expression to platinum resistance in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jakobsen, Anders

    was to investigate if immunohistochemical expression of ERCC1 protein was associated with resistance to standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed ovarian cancer patients. Methods: Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian...

  1. FOXM1 mediates resistance to docetaxel in gastric cancer via up-regulating Stathmin.

    Science.gov (United States)

    Li, Xiaoxiao; Yao, Ruyong; Yue, Lu; Qiu, Wensheng; Qi, Weiwei; Liu, Shihai; Yao, Yasai; Liang, Jun

    2014-05-01

    Docetaxel is commonly used as an effective chemotherapeutic drug for gastric cancer patients recently. With the increasing emergence of docetaxel resistance nowadays, identification of suitable biomarkers for predicting chemosensitivity to docetaxel may be a key role for improving therapeutic effects for gastric cancer patients. In this study, we investigated the correlation between the expression of transcription factor forkhead box protein M1 (FOXM1) and chemotherapy response to docetaxel in gastric cancer, the possible mechanism for which was further explored. As a result, FOXM1 overexpression was shown to mediate resistance to docetaxel in gastric cancers. It altered microtubule dynamics to protect tumour cells from docetaxel-induced apoptosis. Mechanistic investigations revealed that tubulin-destabilizing protein Stathmin, which mediated docetaxel resistance in FOXM1-silenced gastric cancer cells, is a direct down-stream target of FOXM1, whereas another microtubule dynamics protein mitotic centromere-associated kinesin (MCAK), shown to be related to docetaxel resistance in gastric cancer cells, is not associated with FOXM1 expression significantly. These results were further provided by immunohistochemical analysis, indicating that FOXM1 and Stathmin expression levels were correlated in 103 post-operational gastric cancer specimens. Moreover, when we attenuated FOXM1 expression with FOXM1 inhibitor thiostrepton, docetaxel resistance in gastric cancers was found to be reversed, simultaneously with the down-regulation of FOXM1 and Stathmin. Therefore, FOXM1 can be a useful marker for predicting and monitoring docetaxel response. Through the inhibition of FOXM1, docetaxel resistance can be reversed, and thus FOXM1 could be a new therapeutic target in docetaxel-resistant gastric cancer.

  2. The Effect of Prior Androgen Synthesis Inhibition on Outcomes of Subsequent Therapy with Docetaxel in Patients with Metastatic Castrate Resistant Prostate Cancer: Results from a Retrospective Analysis of a Randomized Phase 3 Clinical Trial (CALGB 90401) (Alliance)

    Science.gov (United States)

    Aggarwal, Rahul; Halabi, Susan; Kelly, William Kevin; George, Daniel; Mahoney, John F.; Millard, Frederick; Stadler, Walter M.; Morris, Michael J.; Kantoff, Philip; Monk, J. Paul; Carducci, Michael; Small, Eric J.

    2013-01-01

    Background Preliminary data suggests a potential decreased benefit of docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with abiraterone acetate, a novel androgen synthesis inhibitor (ASI). CALGB 90401 (Alliance), a phase 3 trial of mCRPC patients treated with docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes following docetaxel. Methods CALGB 90401 randomized 1050 men with chemotherapy-naïve, mCRPC to treatment with docetaxel and prednisone with either bevacizumab or placebo. 1005 men (96%) had data available regarding prior ketoconazole therapy. The effect of prior ketoconazole on overall survival (OS), progression-free survival (PFS), PSA decline, and objective response rate (ORR) observed was assessed using proportional hazards and Poisson regression method adjusted for validated prognostic factors and treatment arm. Results Baseline characteristics between patients with (N=277) and without (N=728) prior ketoconazole therapy were similar. There were no statistically significant differences between patients with and without prior ketoconazole therapy with respect to OS (median OS 21.1 vs. 22.3 months, stratified log-rank p-value=0.635); PFS (median PFS 8.1 vs. 8.6 months, stratified log-rank p-value=0.342); ≥50% PSA decline (61% vs. 66%, relative risk=1.09, adjusted p-value=0.129); or ORR (39% vs. 43%, relative risk=1.11, adjusted p-value=0.366). Conclusions As measured by OS, PFS, PSA and ORR, there is no evidence that prior treatment with ketoconazole impacts clinical outcomes in mCRPC patients treated with subsequent docetaxel-based therapy. Prospective studies are needed to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC. PMID:23913744

  3. TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.

    Science.gov (United States)

    Zhang, Song-Fa; Wang, Xin-Yu; Fu, Zhi-Qin; Peng, Qiao-Hua; Zhang, Jian-Yang; Ye, Feng; Fu, Yun-Feng; Zhou, Cai-Yun; Lu, Wei-Guo; Cheng, Xiao-Dong; Xie, Xing

    2015-01-01

    Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients. Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1 expression, increase of autophagosome formation, and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17 inhibition by siRNA or enforced overexpression by a pcDNA3.1(+)-TXNDC17 plasmid correspondingly decreased or increased the autophagy response and paclitaxel resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17 overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17, through participation of BECN1, induces autophagy and consequently results in paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or target in ovarian cancer therapeutics.

  4. Management of patients with metastatic breast cancer.

    Science.gov (United States)

    Cruz Jurado, J; Richart Aznar, P; García Mata, J; Fernández Martínez, R; Peláez Fernández, I; Sampedro Gimeno, T; Galve Calvo, E; Murillo Jaso, L; Polo Marqués, E; García Palomo, A

    2011-09-01

    Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Aromatase inhibitors (AI) have been extensively studied in this setting. This section summarizes the key data regarding the use of AI in advanced breast cancer. In postmenopausal women, AI are the first line of treatment for untreated patients, or those who had prior AI treatment and progress after 12 months of adjuvant therapy. A longer disease-free interval and absence of visceral disease is associated with a better response. If tumors recur in less than 12 months, it is recommended that tamoxifen (TAM) or the estrogen-receptor antagonist fulvestrant (FUL) treatment be initiated. In the second-line setting, the best option after progression is the administration of either FUL or TAM. In the third-line setting, reintroduction of AI is considered an acceptable option. In premenopausal women who have not received prior treatment or who have progressed after 12 months following adjuvant treatment, it is recommended to initiate therapy with a combination of TAM and a luteinizing hormone-releasing hormone (LHRH) analog. If there is treatment failure with the use of this combination, megestrol acetate or an LHRH agonist plus an AI may be reasonable alternatives. Intensive research is ongoing to understand the mechanisms of resistance to hormone therapy. In human epidermal growth factor receptor 2 positive-patients, combinations with HER2 antagonists are associated with significant clinical activity.

  5. Infections in cancer patients: some controversial issues.

    Science.gov (United States)

    Schimpff, S C; Scott, D A; Wade, J C

    1994-03-01

    Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged

  6. Doctors Seeing More HIV Patients with Multidrug Resistance

    Science.gov (United States)

    ... html Doctors Seeing More HIV Patients With Multidrug Resistance People resistant to older medication also have problems ... to modern drugs had HIV mutations linked with resistance to older drugs called thymidine analogues. Among patients ...

  7. Reversing the intractable nature of pancreatic cancer by selectively targeting ALDH-high, therapy-resistant cancer cells.

    Science.gov (United States)

    Kim, Sang Kyum; Kim, Honsoul; Lee, Da-Hye; Kim, Tae-shin; Kim, Tackhoon; Chung, Chaeuk; Koh, Gou Young; Kim, Hoguen; Lim, Dae-Sik

    2013-01-01

    Human pancreatic ductal adenocarcinoma (PDAC) is a cancer with a dismal prognosis. The efficacy of PDAC anticancer therapies is often short-lived; however, there is little information on how this disease entity so frequently gains resistance to treatment. We adopted the concept of cancer stem cells (CSCs) to explain the mechanism of resistance and evaluated the efficacy of a candidate anticancer drug to target these therapy-resistant CSCs. We identified a subpopulation of cells in PDAC with CSC features that were enriched for aldehyde dehydrogenase (ALDH), a marker expressed in certain stem/progenitor cells. These cells were also highly resistant to, and were further enriched by, treatment with gemcitabine. Similarly, surgical specimens from PDAC patients showed that those who had undergone preoperative chemo-radiation therapy more frequently displayed cancers with ALDH strongly positive subpopulations compared with untreated patients. Importantly, these ALDH-high cancer cells were sensitive to disulfiram, an ALDH inhibitor, when tested in vitro. Furthermore, in vivo xenograft studies showed that the effect of disulfiram was additive to that of low-dose gemcitabine when applied in combination. In conclusion, human PDAC-derived cells that express high levels of ALDH show CSC features and have a key role in the development of resistance to anticancer therapies. Disulfiram can be used to suppress this therapy-resistant subpopulation.

  8. Decitabine reactivated pathways in platinum resistant ovarian cancer.

    Science.gov (United States)

    Fang, Fang; Zuo, Qingyao; Pilrose, Jay; Wang, Yinu; Shen, Changyu; Li, Meng; Wulfridge, Phillip; Matei, Daniela; Nephew, Kenneth P

    2014-06-15

    Combination therapy with decitabine, a DNMTi and carboplatin resensitized chemoresistant ovarian cancer (OC) to platinum inducing promising clinical activity. We investigated gene-expression profiles in tumor biopsies to identify decitabine-reactivated pathways associated with clinical response. Gene-expression profiling was performed using RNA from paired tumor biopsies before and 8 days after decitabine from 17 patients with platinum resistant OC. Bioinformatic analysis included unsupervised hierarchical-clustering, pathway and GSEA distinguishing profiles of "responders" (progression-free survival, PFS>6 months) and "non-responders" (PFSdecitabine (TGF-β and Hh). Gene-expression profiling identified specific pathways altered by decitabine and associated with platinum-resensitization and clinical benefit in OC. Our data could influence patient stratification for future studies using epigenetic therapies.

  9. The role of BCAR4 in tamoxifen resistant breast cancer

    NARCIS (Netherlands)

    M.F. Godinho (Marcia)

    2012-01-01

    textabstractBreast cancer is one of the most common cancers in women, and it is the second leading cause of cancer-related deaths, just behind lung cancer. The antiestrogen tamoxifen has been successfully used for over three decades to treat patients with estrogen receptor alpha-positive breast canc

  10. 食管癌患者术后感染病原菌的耐药性检测与分析%Drug resistance of pathogens causing postoperative infections in patients with esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    赵光磊; 谭辉; 田茂松; 潘铁成; 吴林鸿

    2015-01-01

    OBJECTIVE To investigate the drug resistance of pathogens causing postoperative infections in the pa‐tients with esophageal cancer so as to provide guidance for treatment of the postoperative infections .METHODS A total of 235 esophageal cancer patients with postoperative infections who were treated in the hospital from Sep 2011 to Nov 2014 were enrolled in the study .The species of drug‐resistant pathogens causing the infections and the drug resistance were statistically analyzed ,and the statistical analysis of data was performed by using SPSS18 .0 software .RESULTS Totally 312 strains of pathogens have been isolated ,including 254 (81 .41% ) strains of gram‐negative bacteria ,37 (11 .86% ) strains of gram‐positive bacteria ,and 21 (6 .73% ) strains of fungi .The drug re‐sistance rates of the gram‐negative bacteria to ceftriaxone ,mezlocillin ,and ciprofloxacin were more than 50 .00% , and the drug resistance rate to imipenem was less than 33 .00% .The drug resistance rates of the gram‐positive bac‐teria to oxacillin ,penicillin ,azthromycin ,cefazolin ,and ciprofloxacin were more than 50 .00% ,and the drug re‐sistance rate to vancomycin was 0 .CONCLUSION The gram‐negative bacteria are dominant among the drug‐resist‐ant pathogens causing the postoperative infections in the esophageal cancer patients .It is necessary for the hospital to conduct the appropriate treatment according to the drug resistance of the pathogens .%目的:研究分析食管癌患者术后感染病原菌的耐药性,为治疗食管癌术后感染提供依据。方法选取2011年9月-2014年11月医院收治的235例食管癌术后感染患者,统计分析感染患者病原菌种类及其耐药性,采用SPSS18.0软件对数据进行统计分析。结果共分离出病原菌312株,其中革兰阴性菌254株占81.41%,革兰阳性菌37株占11.86%,真菌21株占6.73%;革兰阴性菌对头孢曲松、美洛西林、环丙沙

  11. 食管癌患者放疗后真菌感染危险因素分析%Risk factors of fungal infections in esophageal cancer patients after radiotherapy and analysis of drug resistance

    Institute of Scientific and Technical Information of China (English)

    郑勤红; 廖小方; 胡伟; 彭政; 邹燕; 徐万苏

    2013-01-01

    OBJECTIVE To explore the risk factors of fungal infections in the esophageal cancer patients after the radiotherapy and analyze the drug resistance so as to reduce the incidence of infections.METHODS The clinical data of the 40 cases of esophageal cancer patients who were complicated with fungal infections after the radiotherapy were investigated and analyzed.RESULTS Of totally 40 strains of pathogens isolated,the Candida albicans was the predominant species,accounting for 72.50%,followed by the Trichosporon (12.5%),Candida tropicalis (5.0%),Candida glabrata (5.0%),and Candida krusei (5.0%).The species of pathogens varied in the drug resistance to six antifungal agents,among which the drug resistance rate to voriconazole was up to 55.00%.CONCLUSION Taking comprehensive prevention measures according to the actual situation of the esophageal cancer patients,reasonably using antibiotics,closely monitoring the change of condition of the chemotherapy patients and the radiotherapy patients,intensifying the nutritional and supportive treatment,and improving the patient's immunity can improve the effect of the infection prevention.%目的 探讨食管癌患者放疗后真菌感染危险因素与耐药性,以降低感染的发生.方法 对40例食管癌放疗后真菌感染患者临床资料进行调查分析.结果 共分离出病原菌40株,其中白色假丝酵母菌最高,占72.50%,其余依次为毛孢子菌、热带假丝酵母菌、光滑假丝酵母菌、克柔假丝酵母菌,分别占12.5%、5.0%、5.0%、5.0%;对6种抗真菌药物均有不同程度的耐药性,其中伏立康唑耐药率高达55.00%.结论 根据食管癌患者实际情况采取综合防治措施,合理应用抗菌药物,严密监测化疗、放疗时患者的病情变化,加强营养及支持治疗,提高患者的自身抵抗力,可提高预防感染和抗感染的效果.

  12. BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells

    NARCIS (Netherlands)

    A. Brinkman (Arend); S. van der Flier (Silvia); E.M. Kok (Elisabeth); L.C.J. Dorssers (Lambert)

    2000-01-01

    textabstractBACKGROUND: Treatment of breast cancer with the antiestrogen tamoxifen is effective in approximately one half of the patients with estrogen receptor-positive disease, but tumors recur frequently because of the development of metastases that are resistant to

  13. Psychometric Evaluation of Cancer Patients

    Directory of Open Access Journals (Sweden)

    S B Bansal, Sanjay Dixit, Geeta Shivram

    2012-01-01

    Full Text Available Background: Mental health is the balanced development of the individual’s personality and the emotional attitude which will enable him or her to live harmoniously with his or her Fellow citizens. Mental health is not exclusively a matter of relation between persons It is also a matter of relation of individuals towards the community in which they live, towards the society of which the community is a part, and towards the social institutions which for a large part guide their life, determine their way of living, working, leisure, and the way they spends and earns the money, the way they sees happiness, stability and security. Objective: To asses and quantify the prevalence of psychological morbidity in cancer patients of government cancer hospital MGM Medical College Indore, M.P. Material and Methods: 100 cancer patients were chosen randomly all of them were interviewed through a questionnaire survey in ward and OPD of cancer hospital in November and December 2009. Data on demographics, and duration of diagnosis were collected. Results: Gender wise prevalence of psychological morbidity Grade II &III; were 94% in males and 86% in females. Chi square test was not significant. According to age the Grade II & III psychological morbidity were 41(46% in 15-45 years age group and 49 (54% in 46-75 years age group which is significantly higher than previous age group .Chi square test (x2 = 7.54 p value < 0.05 Grade II & III psychological morbidity were 52% in 0-6 months duration while it was 38% in more than 6 months duration Chi square test (x2= 8.04, P value < 0.05 statistically significant Conclusion: the prevalence of psychological morbidity was slightly higher in males and older age group, and also high psychological morbidity was seen in recently diagnosed cancer patients. A good counseling, stress relaxation and life style modification program is required to make such patients live their life in a positive and better way.

  14. Hormonal therapy and chemotherapy in patients with hormone-sensitive prostate cancer

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2016-01-01

    Full Text Available Prostate cancer is the most common men`s cancer in men in developed world and the second cause of death in this population. This review focuses on management of advanced castration resistant prostate cancer (CRPC has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer.

  15. Exercise and relaxation intervention for patients with advanced lung cancer

    DEFF Research Database (Denmark)

    Adamsen, Lis; Stage, M; Laursen, J

    2012-01-01

    (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home......Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer......-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group...

  16. Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein.

    Directory of Open Access Journals (Sweden)

    Britta Stordal

    Full Text Available The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A, MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy.

  17. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2014-06-01

    Full Text Available Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC. Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  18. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor; Silke Gillessen

    2014-01-01

    Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  19. How circulating tumor cells escape from multidrug resistance: translating molecular mechanisms in metastatic breast cancer treatment.

    Science.gov (United States)

    Gradilone, Angela; Raimondi, Cristina; Naso, Giuseppe; Silvestri, Ida; Repetto, Lazzaro; Palazzo, Antonella; Gianni, Walter; Frati, Luigi; Cortesi, Enrico; Gazzaniga, Paola

    2011-12-01

    Resistance to anthracyclines is responsible for treatment failure in most patients with metastatic breast cancer. According to recent studies, the expression of specific drug transporters (MRPs) on circulating tumor cells is predictive of prognosis in different cancer types. We observed that patients whose circulating tumor cells expressed MRP1 and MRP2, two drug-export pumps responsible for anthracyclines efflux, who received conventional anthracyclines had a significantly shorter time to progression compared with patients sharing same characteristics who received non pegylated liposomal doxorubicin (P < 0.005). These results may highlight a new appealing role of the liposomal doxorubicin formulation, not only because of its reduced cardiac toxicity but especially referring to its theoretical efficacy in anthracycline-resistant breast cancer patients.

  20. Adaptive immune resistance: How cancer protects from immune attack

    Science.gov (United States)

    Ribas, Antoni

    2015-01-01

    Adaptive immune resistance is a process where the cancer changes its phenotype in response to a cytotoxic or pro-inflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1 blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies. PMID:26272491

  1. RON confers lapatinib resistance in HER2-positive breast cancer cells.

    Science.gov (United States)

    Wang, Quanren; Quan, Haitian; Zhao, Jie; Xie, Chengying; Wang, Lei; Lou, Liguang

    2013-10-28

    Lapatinib-resistance is a major problem for HER2-positive breast cancer treatment. SK-BR-3-LR, a lapatinib-resistant cell clone, was established from HER2-positive SK-BR-3 breast cancer cells following chronic exposure to lapatinib. The PI3K/AKT signaling pathway was demonstrated to be resistant to HER2 inhibition in SK-BR-3-LR cells. However, both small-molecular Recepteur d'Origine Nantais (RON) inhibitors and RON-targeted small interfering RNA (siRNA) effectively restored lapatinib sensitivity in these cells by inhibiting PI3K/AKT activation. Our results demonstrate for the first time the important role of RON in mediating lapatinib resistance and suggest that RON-targeted therapy may become a novel, promising therapeutic strategy after the failure of lapatinib treatment in patients with HER2-positive breast cancer.

  2. 肺部肿瘤化疗对癌症患者耐甲氧西林金黄色葡萄球菌(M RSA)的影响%Lung cancer chemotherapy impact on cancer patients with methicillin-resistant Staphylococcus aureus (MRSA)

    Institute of Scientific and Technical Information of China (English)

    阳曼丽

    2016-01-01

    目的:研究癌症患者肺部肿瘤化疗后耐甲氧西林金黄色葡萄球菌(MRSA )变化情况。方法:回顾性分析100例肺部肿瘤化疗患者的 MRSA 感染资料。从感染者鼻、喉和其他感染部位获得 MRSA 定植拭子,进行生物检验。结果:44例患者为 MRSA 携带者。 MRSA 败血症48例,其中42%的患者中性粒细胞计数<500/μl 。 MRSA 致命并发症仅8例。 MRSA 败血病死率为14.6%。结论:化疗抗肿瘤可用于 MRSA 感染的肺癌患者,并且不必减少剂量或延迟治疗。%Objective :To study the lung cancer chemotherapy for cancer patients methicillin‐resistant Staphylococcus aureus (MRSA) .Methods :We retrospectively analyzed the clinical data of 100 cases of lung cancer chemotherapy were MRSA‐infected patients .Results :44 patients were colonized with MRSA ,and 56 patients colo‐nized and / or infected with MRSA .48 cases of MRSA sepsis .In addition ,during MRSA sepsis ,42% of patients with neutrophil count < 500/μl .However ,MRSA only 8cases of fatal complications .MRSA sepsis‐induced mortali‐ty rate was 14 .6% .Conclusion :The anti‐tumor chemotherapy may be administered to a patient with lung cancer MRSA infection ,and does not necessarily reduce the dose or delay treatment .

  3. Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer.

    Science.gov (United States)

    Tsuruta, Masashi; Nishibori, Hideki; Hasegawa, Hirotoshi; Ishii, Yoshiyuki; Endo, Takashi; Kubota, Tetsuro; Kitajima, Masaki; Kitagawa, Yuko

    2008-11-01

    The resistance of colon cancer to 5-fluorouracil (5-FU) is a critical issue, and the cause of this resistance cannot always be explained based on the known molecules. Heat shock protein 27 (HSP27) mRNA expression has recently been shown to be correlated with 5-FU resistance in 5-FU-resistant cell lines. In this study, we attempted to elucidate the functional mechanism of HSP27 in 5-FU resistance in colon cancer. HSP27 protein levels in several human colon cancer cell lines (LoVo, HCT15, WiDr, HCT116, HT-29 and SW480) were determined by immunoblot and densitometry analysis. The in vitro growth inhibition rates (IR) of the cell lines at various concentrations of 5-FU were assessed by MTT assay. The degree of 5-FU resistance was estimated as the drug concentration inducing 50% IR (IC50). The HSP27 protein level and IC50 were significantly correlated in these cell lines (p=0.010). The effect of HSP27 overexpression on IC50 was evaluated in LoVo cells. HSP27 transfectants significantly increased IC50 and reduced HSP27 resistance. The effect of HSP27 down-regulation by HSP27 siRNA on IC50 was confirmed in HCT15 cells. HSP27 siRNA suppressed HSP27 protein levels and reduced IC50 in a dose-dependent manner. These data indicated that HSP27 is closely connected with 5-FU resistance in colon cancer and suggested that HSP27 levels predicted 5-FU resistance. HSP27 down-regulation overcame 5-FU resistance and HSP27 may be a clinical target in patients with 5-FU-resistant colon cancer.

  4. POSTOPERATIVE HYPERGLYCAEMIA IN NON-DIABETIC INDIAN CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    Pampanagouda

    2016-03-01

    Full Text Available There is limited data available in the literature about the hyperglycaemic response in cancer patients in the postoperative period. Hyperglycaemia resulting from insulin resistance is common in critically ill patients including those who have not previously been diagnosed with diabetes. We tried to analyse the glycaemic response in different cancer patients in the postoperative period, so that this information can be analysed to look for any correlation between the glycaemic response and the surgical outcome, in particular cancer patients. Prospectively, the postoperative blood glucose level was measured at different intervals. Hyperglycaemic response was more at 6th hour and gradually declined over next 72 hours. Hyperglycaemic response was more in carcinoma oesophagus patients and least in thyroid patients. The stress of surgery itself results in metabolic perturbations that alter glucose homeostasis. Persistent hyperglycaemia is a risk factor for endothelial dysfunction, impaired phagocytosis and immunity, oxidative stress, abnormal lipid metabolism, decreased vascular contractility, increased platelet adhesiveness and increased C-reactive protein levels, consequently resulting in cardiovascular morbidity, postoperative sepsis and impaired wound healing. Patients with cancer respond differently to stress and this knowledge might help in the future to develop strategies to reduce and treat during the postoperative period. OBJECTIVE To study the pattern of glycaemic variation in patients with different Cancers during the postoperative period.

  5. Psychiatric Problems in Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Munevver Tunel

    2012-06-01

    Full Text Available Cancer is a physical disorder with concurrent mental and social components. During cancer, the feelings of fear, hopelessness, guilt, helplessness, abandonment perceived as a crisis leading to destruction in the suffering person. Breast cancer is the most common type of cancer among women. Prevalence of psychiatric disorders among cancer patients is approximately 50% and most of disorders are related with the occurrence of cancer and cancer treatment. Majority of patients present with major depression, adjustment disorder, anxiety disorders, sleep disorders, suicidial ideation, and delirium. Treatment of psychiatric disorders and cancer therapy should be conducted along with special consideration of drug interactions. This article reviews the adaptation process experienced by individuals during diagnosis and treatment of breast cancer, it psychological effects, resulting psychiatric comorbidites and their treatments. [Archives Medical Review Journal 2012; 21(3.000: 189-219

  6. Disulfiram targets cancer stem-like cells and reverses resistance and cross-resistance in acquired paclitaxel-resistant triple-negative breast cancer cells

    Science.gov (United States)

    Liu, P; Kumar, I S; Brown, S; Kannappan, V; Tawari, P E; Tang, J Z; Jiang, W; Armesilla, A L; Darling, J L; Wang, W

    2013-01-01

    Background: Triple-negative breast cancer (TNBC) has significantly worse prognosis. Acquired chemoresistance remains the major cause of therapeutic failure of TNBC. In clinic, the relapsed TNBC is commonly pan-resistant to various drugs with completely different resistant mechanisms. Investigation of the mechanisms and development of new drugs to target pan-chemoresistance will potentially improve the therapeutic outcomes of TNBC patients. Methods: In this study, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI)–isobologram, western blot, ALDEFLUOR analysis, clonogenic assay and immunocytochemistry were used. Results: The chemoresistant MDA-MB-231PAC10 cells are highly cross-resistant to paclitaxel (PAC), cisplatin (CDDP), docetaxel and doxorubicin. The MDA-MB-231PAC10 cells are quiescent with significantly longer doubling time (64.9 vs 31.7 h). This may be caused by high expression of p21Waf1. The MDA-MB-231PAC10 cells express high aldehyde dehydrogenase (ALDH) activity and a panel of embryonic stem cell-related proteins, for example, Oct4, Sox2, Nanog and nuclealisation of HIF2α and NF-κBp65. We have previously reported that disulfiram (DS), an antialcoholism drug, targets cancer stem cells (CSCs) and enhances cytotoxicity of anticancer drugs. Disulfiram abolished CSC characters and completely reversed PAC and CDDP resistance in MDA-MB-231PAC10 cells. Conclusion: Cancer stem cells may be responsible for acquired pan-chemoresistance. As a drug used in clinic, DS may be repurposed as a CSC inhibitor to reverse the acquired pan-chemoresistance. PMID:24008666

  7. 头颈部肿瘤患者口腔真菌感染耐药性分析%Drug resistance of fungi causing oral infections in patients with head and neck cancer

    Institute of Scientific and Technical Information of China (English)

    郑晓珍; 郑勤红; 邹燕; 吕珍; 王丹丹

    2014-01-01

    OBJECTIVE To analyze the drug resistance of the fungi causing oral infections in head and neck cancer patients undergoing radiochemotherapy so as to provide guidance for clinical treatment .METHODS A total of 605 patients with head and neck cancer ,who underwent the radiochemotherapy from Jan 2009 to Sep 2013 ,were en-rolled in the study ,then the throat swab samples were collected from the patients with infections ,the drug resist-ance of isolated fungi was analyzed ;the statistical analysis was performed with the use of SPSS 17 .0 software ,the measurement data were defined as mean ± standard deviation and analyzed by using the t-test ,and the count data were analyzed by means of the chi-square test .RESULTS Among the 605 head and neck cancer patients undergoing radiochemotherapy ,the oral infections occurred in 63 cases with the infection rate of 10 .41% .Totally 125 strains of pathogens have been isolated ,including 61 (48 .80% ) strains of bacteria and 64 (51 .20% ) strains of fungi;the Candida albicans was dominant among the fungi ,accounting for 24 .80% (31 strains ) .The main species of fungi were highly resistant to econazole and ketoconazole ,but the drug resistance rates to fluconazole ,5-flucytosine , and amphotericin B were low ,and the strains were most susceptible to amphotericin B ,with the drug resistance rate no more than 3 .23% .CONCLUSION The incidence of fungal infections is high in the head and neck cancer pa-tients undergoing radiochemotherapy ,and the C .albicans is the predominant species of fungi .Fluconazole can achieve significant effect on treatment of the fungal infections ,meanwhile ,flucytosine and amphotericin B can also be applied in the hospital .%目的:针对头颈部肿瘤放化疗患者口腔感染及真菌耐药性进行分析,为临床治疗提供参考依据。方法对2009年1月-2013年9月收治的605例头颈部肿瘤放化疗患者口腔咽拭子样本进行感染分析,并对检出真菌进

  8. State-Of-The-Art Treatment in Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Elena Castro

    2014-11-01

    Full Text Available Prostate cancer (PrCa is the most common cancer type in men in developed countries. In the last few years, a dramatic change has occurred in the understanding of castration-resistant PrCa which has led to the development of new drugs that have an impact on patient survival. This review summarises the recent advances in the management of the disease.

  9. Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

    Institute of Scientific and Technical Information of China (English)

    Ji-Heng Wang; Jing-Ping Du; Ying-Hai Zhang; Xiao-Jun Zhao; Ru-Ying Fan; Zhi-Hong Wang; Zi-Tao Wu; Ying Han

    2011-01-01

    AIM: To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy. METHODS: A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established,and the expression of PrPc, Bcl-2 and Bax was detected in these cells. Apoptosis was determined using Annexin V staining. Western blotting and immunohistochemistry were performed to detect the expression of PrPc in patients receiving chemotherapy and to explore the role of PrPc expression in predicting the chemosensitivity and the outcome of gastric cancer patients receiving chemotherapy. Follow-up was performed for 2 years. RESULTS: PrPc expression was increased with the increase in drug resistance. Bcl-2, together with PrPc, increased the level of anti-apoptosis of cancer cells. Increased PrPc expression predicted the enhanced level of anti-apoptosis and resistance to anticancer drugs. PrPc expression could be used as a marker for predicting the efficacy of chemotherapy and the prognosis of gastric cancer. Increased PrPc expression predicted both poor chemosensitivity and a low 2-year survival rate. Contrarily, low PrPc expression predicted favorable chemosensitivity and a relatively high 2-year survival rate.CONCLUSION: PrPc expression is associated with histological types and differentiation of gastric cancer cells; The PrPc expression level might be a valuable marker in predicting the efficacy of chemotherapy and the prognosis of gastric cancer patients receiving chemotherapy.

  10. Extracellular Vesicle-Mediated Reversal of Paclitaxel Resistance in Prostate Cancer

    Science.gov (United States)

    Wang, Justin Q.; DeChalus, Austin; Chatterjee, Devin N.; Keller, Evan T.; Mizokami, Atsushi; Camussi, Giovanni; Mendelsohn, Andrew R.; Renzulli, Joseph F.; Quesenberry, Peter J.; Chatterjee, Devasis

    2017-01-01

    Prostate cancer (PCa) is the most common solid tumor in males and the second leading cause of cancer-related deaths in males in the United States. The current first line therapy for metastatic PCa is androgen deprivation therapy and is initially effective against the disease. However, castrate resistant prostate cancer (CRPC) develops in many men within 18–36 months, rendering this treatment ineffective. Chemotherapy, with a class of drugs known as taxanes is the standard-of-care cytotoxic option in metastatic castrate resistant PCa (mCRPC). However, the overall survival advantage for chemotherapy in mCRPC is only 2.2 months and the cancer cells often become resistant to these drugs as well. Once patients fail chemotherapy the progression to death is inevitable. Extracellular vesicles (EVs) are involved in cell signaling and play a role in cancer progression. Previous work has demonstrated that EVs are involved in the development of drug resistance in cancer cells. We report the reversal of taxane resistance and tumorigenic phenotype in PCa cells after EVs treatment. This study suggests that EVs represent a potentially novel therapeutic treatment option for CRPC. PMID:27279238

  11. Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol.

    Science.gov (United States)

    Fu, Aiqin; Yu, Ze; Song, Yaobo; Zhang, Enning

    2015-06-01

    Taxol is a front‑line chemotherapeutic agent for the treatment of patients with multiple types of tumor. However, resistance to Taxol remains one of the principal causes of cancer‑associated mortality. Glutamine, which is metabolized via a glutaminase (GLS)‑dependent process, termed glutaminolysis, is important in cell growth and metabolism. The present study reported a novel mechanism underlying Taxol resistance in breast cancer cells. By investigating the glutamine metabolism of breast cancer cells in response to treatment with Taxol in vitro, it was observed that Taxol induced the uptake of glutamine and the expression of GLS1. Notably, Taxol‑resistant cancer cells exhibited upregulation in the metabolism of glutamine and expression of GLS1. In addition, overexpression of GLS1 rendered cancer cells resistant to Taxol, indicating that GLS1 may be the therapeutic target for overcoming Taxol resistance in clinical therapeutics. The results also demonstrated that knock‑down of GLS1 using small interfering RNA, resensitized the Taxol‑resistant breast cancer cells to Taxol.

  12. Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

    Science.gov (United States)

    Ai, Zhihong; Lu, Yang; Qiu, Songbo; Fan, Zhen

    2016-04-01

    Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable α subunit of HIF-1, HIF-1α, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1α degradation but did not downregulate HIF-1α in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1α (HIF-1α ΔODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1α or pharmacological promotion of HIF-1α degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1α improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1α-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer.

  13. Ulinastatin reduces the resistance of liver cancer cells to epirubicin by inhibiting autophagy.

    Directory of Open Access Journals (Sweden)

    Bin Song

    Full Text Available During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI, a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI. We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells, and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy.

  14. 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

    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...

  15. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  16. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer

    Science.gov (United States)

    Somasagara, Ranganatha R.; Tripathi, Kaushlendra; Spencer, Sebastian M.; Clark, David W.; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P.; Piazza, Gary A.; Palle, Komaraiah

    2015-01-01

    Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize β-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer. PMID:26679603

  17. Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

    Directory of Open Access Journals (Sweden)

    Bordón Elisa

    2011-06-01

    Full Text Available Abstract Background Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13 was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp. Radiation-induced apoptosis (RIA at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46. Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively. We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively in multivariate analysis. Conclusions A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low

  18. Current Status of Methods to Assess Cancer Drug Resistance

    Directory of Open Access Journals (Sweden)

    Theodor H. Lippert, Hans-Jörg Ruoff, Manfred Volm

    2011-01-01

    Full Text Available Drug resistance is the main cause of the failure of chemotherapy of malignant tumors, resistance being either preexisting (intrinsic resistance or induced by the drugs (acquired resistance. At present, resistance is usually diagnosed during treatment after a long period of drug administration.In the present paper, methods for a rapid assessment of drug resistance are described. Three main classes of test procedures can be found in the literature, i.e. fresh tumor cell culture tests, cancer biomarker tests and positron emission tomography (PET tests. The methods are based on the evaluation of molecular processes, i.e. metabolic activities of cancer cells. Drug resistance can be diagnosed before treatment in-vitro with fresh tumor cell culture tests, and after a short time of treatment in-vivo with PET tests. Cancer biomarker tests, for which great potential has been predicted, are largely still in the development stage. Individual resistance surveillance with tests delivering rapid results signifies progress in cancer therapy management, by providing the possibility to avoid drug therapies that are ineffective and only harmful.

  19. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

  20. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

    LENUS (Irish Health Repository)

    Doherty, Ben

    2014-01-01

    KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

  1. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm;

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra...

  2. 恶性肿瘤患者放化疗后真菌感染危险因素与耐药分析%Risk factors for fungal infection in cancer patients after chemotherapy of radiotherapy and drug resistance analysis

    Institute of Scientific and Technical Information of China (English)

    吕世良; 贾勇士; 吴树强

    2011-01-01

    OBJECTIVE To analyze the pathogen distribution of specimens causing fungal infection in cancer patients after chemotherapy and chemotherapy and the risk factors that induce fungal infection, so as to effectively prevent and control the fungal infection. METHODS A total of 489 samples of sputum effusion, urine, feces and blood,submitted from Sep 2007 to Jun 2010 were performed the fungal culture and the results of drug susceptibility testing were analyzed. RESULTS Check out a total of 489 cases of patients with 72 strains of fungi, the positive rate was 14. 72% (11. 2% ~ 16.0%), of which Candida albicans is most common, accounting for 70. 83%,followed by a smooth read cocci 13.89%. Age, overuse of antibiotics, hormones and invasive procedures were risk factors for fungal infection. All fungi showed high resistance rate to various antifungal agents such as itraconazole (ITC), amphotericin B (AMB), nystatin (NYS), enconazole (ECO), ketoconazole (KET), miconazole (MIC),ect. Especially for ECO and KET, the resistance rates were as high as 23.61% and 26.39%. The resistance rates to NYS and MIC were over 12.00%. CONCLUSION To rationally use antifungal agents according to the results of drug susceptibility tests, prevent the abuse of antibiotics and control cancer patients caused by needles during the treatment and drug resistance of pathogens can guide the rational application of antibiotics in clinics.%目的 分析恶性肿瘤患者放化疗后真菌感染的菌种分布特征和诱发真菌感染的危险因素以及耐药性,从而对医院真菌感染进行有效的预防和及时的控制.方法对医院2007年9月-2010年6月送检的489份患者痰液、胸腹水、尿液、粪便及血液等标本进行真菌培养及药敏试验分析.结果 489例患者共检查出真菌72株,阳性率为14.72%,其中以白色假丝酵母菌最为常见,占70.83%,其次是热带假丝酵母菌占13.89%;恶性肿瘤放化疗、抗菌药物的滥用,激素及

  3. Sipuleucel-T: in metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Plosker, Greg L

    2011-01-01

    Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T, patients undergo a leukapheresis procedure for collection of autologous peripheral blood mononuclear cells. Preparation of sipuleucel-T involves enrichment for antigen-presenting cells from the leukapheresis product and activation ex vivo with a recombinant fusion protein (PA2024). In the randomized, double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC, sipuleucel-T was associated with a 22% relative reduction in the risk of death (hazard ratio 0.78; p = 0.03), which was the primary endpoint of the trial. After a median follow-up period of 34.1 months, median survival was 4.1 months longer with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant between-group difference for the median time to objective disease progression (a secondary endpoint). Almost all patients treated with sipuleucel-T in clinical trials reported an adverse event, although these were mild or moderate in severity (grade 1 or 2) in most patients. The most common adverse events (e.g. infusion-related events, such as chills and fever) generally occurred within the first day after administration of sipuleucel-T and resolved within 2 days.

  4. miR-21 Expression in Cancer Cells may Not Predict Resistance to Adjuvant Trastuzumab in Primary Breast Cancer

    DEFF Research Database (Denmark)

    Nielsen, Boye Schnack; Balslev, Eva; Poulsen, Tim Svenstrup

    2014-01-01

    , predominantly in cancer cells, or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict...... expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p = 0.69) or the stromal cells population (p = 0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance......Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute...

  5. Skin cancer in patients with psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Thyssen, J P; Gislason, G H

    2016-01-01

    BACKGROUND: Psoriasis is a chronic inflammatory skin disease that is commonly treated with ultraviolet phototherapy and systemic immunosuppressant drugs, which may confer a risk of skin cancer. Previous studies on the risk of skin cancer in patients with psoriasis have shown conflicting results....... OBJECTIVES: We investigated the risk of new-onset melanoma and non-melanoma skin cancer (NMSC), respectively, in a large cohort of patients with psoriasis and psoriatic arthritis. METHODS: Data on all Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2012 were linked at individual...... of skin cancer is only modestly increased in patients with psoriasis, clinicians should remain vigilant....

  6. Fostering hope in the patient with cancer.

    Science.gov (United States)

    Lichwala, Rebecca

    2014-06-01

    When a patient is diagnosed with cancer, feelings such as fear, anxiety, and hopelessness can negatively affect a person's frame of mind. Hope can help a patient decrease anxiety and increase quality of life. Nurses should assess hope, provide interventions, be empathetic, listen, and treat patients with dignity to help improve hope and quality of life. This article features how hope can have a positive impact and provides specific information about how nurses can promote and foster hope in patients with cancer.

  7. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA.

    Science.gov (United States)

    Murtaza, Muhammed; Dawson, Sarah-Jane; Tsui, Dana W Y; Gale, Davina; Forshew, Tim; Piskorz, Anna M; Parkinson, Christine; Chin, Suet-Feung; Kingsbury, Zoya; Wong, Alvin S C; Marass, Francesco; Humphray, Sean; Hadfield, James; Bentley, David; Chin, Tan Min; Brenton, James D; Caldas, Carlos; Rosenfeld, Nitzan

    2013-05-02

    Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection. Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a non-invasive liquid biopsy. Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over 1-2 years. For each case, exome sequencing was performed on 2-5 plasma samples (19 in total) spanning multiple courses of treatment, at selected time points when the allele fraction of tumour mutations in plasma was high, allowing improved sensitivity. For two cases, synchronous biopsies were also analysed, confirming genome-wide representation of the tumour genome in plasma. Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance. These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel; a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin; a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab, and following subsequent treatment with lapatinib, a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib. These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify

  8. Resistance to cancer treatment: the role of somatic genetic events and the challenges for targeted therapies

    Directory of Open Access Journals (Sweden)

    Gerald eBatist

    2011-10-01

    Full Text Available Therapeutic resistance remains a major cause of cancer-related deaths. Resistance can occur from the outset of treatment or as an acquired phenomenon after an initial clinical response. Therapeutic resistance is an almost universal phenomenon in the treatment of metastatic cancers. The advent of molecularly targeted treatments brought greater efficacy in patients whose tumors express a particular target or molecular signature. However, resistance remains a predictable challenge. This article provides an overview of somatic genomic events that confer resistance to cancer therapies. Some examples, including BCR-ABL, EML4-ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. There are also examples of somatic genetic changes in other genes or pathways that result in resistance by circumventing the inhibitor, as in resistance to trastuzumab and BRAF inhibitors. Yet other examples results in activation of cytoprotective genes. The fact that all of these mechanisms of resistance are due to somatic changes in the tumor’s genome makes targeting them selectively a feasible goal. To identify and validate these changes, it is important to obtain biopsies o

  9. Safety of anticoagulant treatment in cancer patients

    NARCIS (Netherlands)

    Wilts, Ineke Theodora; Bleker, Suzanne Mariella; Van Es, Nick; Buller, Harry Roger; Di Nisio, Marcello; Kamphuisen, Pieter Willem

    2015-01-01

    Introduction: Patients with cancer are at increased risk of (recurrent) venous thronnboembolism. They are also at increased risk of bleeding. This makes treatment of venous thromboembolisms (VTE) in cancer patients challenging. Areas covered: In this review, we will focus on the safety of anticoagul

  10. Drug resistance in cancer: molecular evolution and compensatory proliferation.

    Science.gov (United States)

    Friedman, Ran

    2016-03-15

    Targeted therapies have revolutionized cancer treatment. Unfortunately, their success is limited due to the development of drug resistance within the tumor, which is an evolutionary process. Understanding how drug resistance evolves is a prerequisite to a better success of targeted therapies. Resistance is usually explained as a response to evolutionary pressure imposed by treatment. Thus, evolutionary understanding can and should be used in the design and treatment of cancer. In this article, drug-resistance to targeted therapies is reviewed from an evolutionary standpoint. The concept of apoptosis-induced compensatory proliferation (AICP) is developed. It is shown that AICP helps to explain some of the phenomena that are observed experimentally in cancers. Finally, potential drug targets are suggested in light of AICP.

  11. MicroRNAs and cancer resistance: A new molecular plot.

    Science.gov (United States)

    Fanini, F; Fabbri, M

    2016-05-01

    The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy.

  12. The expression and significance of P-glycoprotein, lung resistance protein and multidrug resistance-associated protein in gastric cancer

    Directory of Open Access Journals (Sweden)

    Li Yan

    2009-11-01

    Full Text Available Abstract Background To detect the expression of multidrug resistance molecules P-glycoprotein (P-gp, Lung resistnce protein (LRP and Multidrug resistance-associated protein (MRP and analyze the relationship between them and the clinico-pathological features. Methods The expressions of P-gp, LRP and MRP in formalin-fixed paraffin-embedded tissue sections from 59 gastric cancer patients were determined by a labbelled Streptavidin-Peroxidase (SP immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results The positive rates of P-gp, LRP, MRP were 86.4%, 84.7% and 27.1%, respectively. The difference between the positive rate of P-gp and MRP was significant statistically, as well as the difference between the expression of MRP and LRP. No significant difference was observed between P-gp and LRP, but the positively correlation between the expression of P-gp and LRP had been found. No significant correlation between the expression of P-gp, LRP, MRP and the grade of differentiation were observed. The expression of P-gp was correlated with clinical stages positively (r = 0.742, but the difference with the expression of P-gp in different stages was not significant. Conclusion The expressions of P-gp, LRP and MRP in patients with gastric cancer without prior chemotherapy are high, indicating that innate drug resistance may exist in gastric cancer.

  13. The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer

    DEFF Research Database (Denmark)

    Lin, Xue; Stenvang, Jan; Rasmussen, Mads Heilskov;

    2015-01-01

    or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of 'DNA methylation entropy......' to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences...... by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy....

  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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  15. The multidrug resistance 1 (MDR1) gene polymorphism G-rs3789243-A is not associated with disease susceptibility in Norwegian patients with colorectal adenoma and colorectal cancer; a case control study

    DEFF Research Database (Denmark)

    Andersen, V.; Agerstjerne, L.; Jensen, D.;

    2009-01-01

    Background: Smoking, dietary factors, and alcohol consumption are known life style factors contributing to gastrointestinal carcinogenesis. Genetic variations in carcinogen handling may affect cancer risk. The multidrug resistance 1(MDR1/ABCB1) gene encodes the transport protein P-glycoprotein (a...

  16. The lipid peroxidation in breast cancer patients.

    Science.gov (United States)

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Jeziorski, Arkadiusz; Piekarski, Janusz

    2010-06-01

    The aim of our study was to estimate oxidative stress (by using different biomarkers of lipid peroxidation--isoprostanes and thiobarbituric acid reactive substances (TBARS)) in patients with invasive breast cancer, patients with benign breast diseases and in a control group. We observed a statistically increased level of TBARS in plasma and isoprostanes in urine of patients with invasive breast cancer in comparison with a control group. The concentration of tested biomarkers in plasma or urine from patients with invasive breast cancer was also higher than in patients with benign breast diseases. Moreover, the levels of tested markers in patients with benign breast diseases and in a control group did not differ. Considering the data presented in this study, we suggest that free radicals induce peroxidation of unsaturated fatty acid in patients with breast cancer.

  17. Unravelling mechanisms of cisplatin sensitivity and resistance in testicular cancer

    NARCIS (Netherlands)

    Koster, R.; van Vugt, M. A. T. M.; Timmer-Bosscha, H.; Gietema, J. A.; de Jong, S.

    2013-01-01

    Testicular cancer is the most frequent solid malignant tumour type in men 20-40 years of age. At the time of diagnosis up to 50% of the patients suffer from metastatic disease. In contrast to most other metastatic solid tumours, the majority of metastatic testicular cancer patients can be cured with

  18. Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

    DEFF Research Database (Denmark)

    Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K;

    2012-01-01

    The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

  19. Internet health resources and the cancer patient.

    Science.gov (United States)

    Huang, George J; Penson, David F

    2008-03-01

    The last decade has witnessed an explosion of online information regarding cancer and healthcare. Accompanying this has been a large body of research analyzing the quality of this information, how patients perceive these data and how this affects the doctor-patient relationship. This report reviews this literature, summarizing the current state of internet health resources available to the cancer patient and identifying areas for future research. Studies indicate that there are considerable internet resources available to cancer patients and that patients are using these resources as secondary information sources. Specifically, studies indicate that 16-64% of patients are using the internet to obtain health information. For the most part, patients perceive the online information to be reliable but maintain a healthy degree of skepticism. Studies objectively evaluating cancer information on the internet indicate that there is reasonable quality, although the language level of many sites is higher than that of the average American, which may limit the utility of the websites. Finally, while there is widespread internet use by physicians, healthcare providers are skeptical of their patients' ability to use the internet and may even be somewhat threatened by it. In summary, while there is a fairly large literature on internet resources available to the cancer patient, more research is needed. Specifically, it is important to better understand how patients access health information online and their associated preferences so that we can improve cancer patient's access to high quality health information on the internet to facilitate decision-making and health outcomes.

  20. Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer.

    Science.gov (United States)

    Xiong, Rui; Patel, Hitisha K; Gutgesell, Lauren M; Zhao, Jiong; Delgado-Rivera, Loruhama; Pham, Thao N D; Zhao, Huiping; Carlson, Kathryn; Martin, Teresa; Katzenellenbogen, John A; Moore, Terry W; Tonetti, Debra A; Thatcher, Gregory R J

    2016-01-14

    Almost 70% of breast cancers are estrogen receptor α (ERα) positive. Tamoxifen, a selective estrogen receptor modulator (SERM), represents the standard of care for many patients; however, 30-50% develop resistance, underlining the need for alternative therapeutics. Paradoxically, agonists at ERα such as estradiol (E2) have demonstrated clinical efficacy in patients with heavily treated breast cancer, although side effects in gynecological tissues are unacceptable. A drug that selectively mimics the actions of E2 in breast cancer therapy but minimizes estrogenic effects in other tissues is a novel, therapeutic alternative. We hypothesized that a selective human estrogen receptor partial agonist (ShERPA) at ERα would provide such an agent. Novel benzothiophene derivatives with nanomolar potency in breast cancer cell cultures were designed. Several showed partial agonist activity, with potency of 0.8-76 nM, mimicking E2 in inhibiting growth of tamoxifen-resistant breast cancer cell lines. Three ShERPAs were tested and validated in xenograft models of endocrine-independent and tamoxifen-resistant breast cancer, and in contrast to E2, ShERPAs did not cause significant uterine growth.

  1. Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Isozaki, Hideko [Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Takigawa, Nagio, E-mail: ntakigaw@gmail.com [Department of General Internal Medicine 4, Kawasaki Medical School, Okayama 700-8505 (Japan); Kiura, Katsuyuki [Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama 700-8558 (Japan)

    2015-04-30

    The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed. Although these ALK-TKIs show an excellent response initially, most patients eventually acquire resistance. Therefore, careful consideration of the resistance mechanisms might lead to superior therapeutic strategies. Here, we summarize the history of ALK-TKIs and their underlying resistance mechanisms in both the preclinical and clinical settings. In addition, we discuss potential future treatment strategies in ALK-TKI-naïve and -resistant patients with lung cancer harboring the EML4-ALK fusion gene.

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

    Institute of Scientific and Technical Information of China (English)

    Fei Zhou; Caicun Zhou

    2015-01-01

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

  3. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

    Science.gov (United States)

    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  4. MiR-146-SIAH2-AR Signaling in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2015-09-01

    clinical response and PCa patients invariably relapse with more aggressive Castration-Resistant Prostate Cancer (CRPC). The mechanism of CRPC development...blocks AR-signaling often fails after significant initial clinical response and PCa patients invariably relapse with more aggressive form of PCa...proliferation of both parental LNCaP and MDAPCa2b cells but DHT did not increase proliferation of miR-146a inhibitor expressing cell lines (Fig. 6

  5. Endocrine resistance in breast cancer--An overview and update.

    Science.gov (United States)

    Clarke, Robert; Tyson, John J; Dixon, J Michael

    2015-12-15

    Tumors that express detectable levels of the product of the ESR1 gene (estrogen receptor-α; ERα) represent the single largest molecular subtype of breast cancer. More women eventually die from ERα+ breast cancer than from either HER2+ disease (almost half of which also express ERα) and/or from triple negative breast cancer (ERα-negative, progesterone receptor-negative, and HER2-negative). Antiestrogens and aromatase inhibitors are largely indistinguishable from each other in their abilities to improve overall survival and almost 50% of ERα+ breast cancers will eventually fail one or more of these endocrine interventions. The precise reasons why these therapies fail in ERα+ breast cancer remain largely unknown. Pharmacogenetic explanations for Tamoxifen resistance are controversial. The role of ERα mutations in endocrine resistance remains unclear. Targeting the growth factors and oncogenes most strongly correlated with endocrine resistance has proven mostly disappointing in their abilities to improve overall survival substantially, particularly in the metastatic setting. Nonetheless, there are new concepts in endocrine resistance that integrate molecular signaling, cellular metabolism, and stress responses including endoplasmic reticulum stress and the unfolded protein response (UPR) that provide novel insights and suggest innovative therapeutic targets. Encouraging evidence that drug combinations with CDK4/CDK6 inhibitors can extend recurrence free survival may yet translate to improvements in overall survival. Whether the improvements seen with immunotherapy in other cancers can be achieved in breast cancer remains to be determined, particularly for ERα+ breast cancers. This review explores the basic mechanisms of resistance to endocrine therapies, concluding with some new insights from systems biology approaches further implicating autophagy and the UPR in detail, and a brief discussion of exciting new avenues and future prospects.

  6. Cancer surveillance of patients from familial pancreatic cancer kindreds.

    Science.gov (United States)

    Brentnall, T A

    2000-05-01

    The family history can be used to determine which family members warrant surveillance and when to start it. Surveillance should be started at least 1 decade before the earliest age of pancreatic cancer in the family. EUS is the basic, least-invasive surveillance tool; however, findings are similar to those seen in chronic pancreatitis. All patients who have a positive EUS or who have symptoms warrant ERCP. Changes on ERCP of ductal stricturing and clubbed or saccular side branches are suggestive of patients who may need pancreatectomy in the setting of hereditary pancreatic cancer. The goal for surveillance of familial pancreatic cancer patients is to diagnose them before the development of cancer, when they have dysplasia or carcinoma in situ, and to perform a complete pancreatectomy. Timing is crucial for determining when a patient warrants surgery; if performed too early, the patient is put at risk for the morbidity and mortality of a total pancreatectomy, which is not inconsequential. If the patient survives the operation, he or she is often left a brittle diabetic. The alternative of diagnosing too late is more worrisome because the patient dies of pancreatic cancer. An essential ingredient to a good patient outcome is a team approach to these patients, using gastroenterologists, surgeons, and pathologists who have expertise and interest in pancreatic disease.

  7. Prognostic factors in young ovarian cancer patients

    DEFF Research Database (Denmark)

    Klar, M; Hasenburg, A; Hasanov, M;

    2016-01-01

    OBJECTIVES: We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients 40 years of age with advanced epithelial ovarian cancer. METHODS: A total of 5055 patients...... epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles. RESULTS: For patients

  8. Cancer patients and characteristics of pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Hasenberg, U.; Paul, T. [Department of Radiology, University Hospital Essen (Germany); Feuersenger, A. [Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen (Germany); Goyen, M. [Department of Radiology, University Medical Center Hamburg-Eppendorf (Germany); Kroeger, K. [Department of Angiology, University Hospital Essen (Germany)], E-mail: knut.kroeger@uk-essen.de

    2009-03-15

    Objective: To check the hypothesis that cancer patients suffer from extended pulmonary embolism (PE) more frequently than patients without cancer we analysed PEs proved by computed tomography (CT)-imaging. Patients and methods: One hundred and fifty consecutive CT scans at the University Hospital of Essen from March 2002 until December 2004 which proved a definite case of pulmonary embolism were retrospectively reviewed (79 men, 71 women; mean age 57 {+-} 15 years). Underlying disease and blood parameters were included (haemoglobin, haematocrit, fibrinogen and total protein, if determined within 48 h before the CT scans). Results: Patients with malignant disease were older (59 {+-} 12 years vs. 54 {+-} 19 years, p = 0.05) and tend to have a higher rate of central PEs (52% vs. 34%, p = 0.08) than patients without malignancies. The odds of a central PE in cancer patients was about twice as high as in patients without a malignant disease (Odds ratio: 2.08, 95%-confidence interval: 1.06-4.10; age-adjusted Odds ratio 1.88, 95%-confidence interval: 0.92-3.84). Additional adjustment for the clinical information dyspnoea, inhospital patient and clinically expected PE did not deteriorate the odds. Thrombus density determined in patients with central PE only shows a trend towards a lower density in patients with malignant disease (52 {+-} 13 HE vs. 45 {+-} 15 HE, p = 0.13). There is no statistical evidence that thrombus density is related to one of the blood parameters or even blood density measured in the pulmonary artery. Conclusion: Although this is a retrospective study including a small number of patients it shows that cancer patients are at a higher risk for central PE than patients without cancer. Characteristics of the intrapulmonal thrombus in cancer and non-cancer patients seem to be different.

  9. Oral cancer knowledge among Turkish dental patients

    Directory of Open Access Journals (Sweden)

    Melda Misirlioglu

    2013-01-01

    Full Text Available Aims: To determine the level of oral cancer awareness and knowledge among patients referred to the Department of Oral and Maxillofacial Radiology in Central Anatolia. Settings and Design: The study was conducted with 1,125 patients who applied to the school of dentistry for routine dental examinations. The authors collect information with a 20-item written questionnaire from the participants about oral cancer risk factors, epidemiology, etiology, and signs and symptoms. Statistical Analysis: Descriptive statistics of demographic variables and other data were reported as means and percentages. Statistical analysis was performed by means of SPSS +11.0 statistical package. Results: Overall, only 48.9% of all patients showed awareness of oral cancer, with awareness especially poor among lower socioeconomic groups. Awareness of oral cancer risk factors and signs and symptoms did not vary significantly between men and women (P > 0.5; however, older participants (aged 40-64 years were more familiar with oral cancer signs than younger participants. More than half of all participants (56.8% were unaware of the common clinical presentations of oral cancer. Conclusions: The results of this survey showed knowledge regarding oral cancer to be quite low. Thus, educational programs are needed to increase public awareness about oral cancer, and dentists should request patients undergo examinations for oral cancer to ensure early detection.

  10. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients.

    Science.gov (United States)

    Gazzaniga, Paola; Gradilone, Angela; Petracca, Arianna; Nicolazzo, Chiara; Raimondi, Cristina; Iacovelli, Roberto; Naso, Giuseppe; Cortesi, Enrico

    2010-08-01

    The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) and particularly a subpopulation of more aggressive, stem-like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L-OHP) and 5-fluoruracil (5-FU) based regimens. Forty patients with metastatic colorectal cancer were enrolled. CTCs were isolated from peripheral blood and analysed for the expression of aldheyde dehydrogenase 1 (ALDH1), CD44, CD133 (used as markers of stemness), multidrug resistance related protein 5 (MRP5 used as marker of resistance to 5-FU and L-OHP) and survivin (used as a marker of apoptosis resistance). CTCs were found in 27/40 (67%) patients. No correlation was found between the expression of either CD44 and CD133 in CTCs and the outcome of patients, while a statistically significant shorter progression-free survival was found in patients with CTCs positive for the expression of ALDH1, survivin and MRP5. These results support the idea that isolating survivin and MRP5+ CTCs may help in the selection of metastatic colorectal cancer patients resistant to standard 5-FU and L-OHP based chemotherapy, for which alternative regimens may be appropriate.

  11. Cancer in Patients With Gabapentin (GPRD)

    Science.gov (United States)

    2012-02-02

    Pain, Neuropathic; Epilepsy; Renal Pelvis Cancer; Pancreatic Cancer; Breast Cancer; Nervous System Cancer; Chronic Pancreatitis; Stomach Cancer; Renal Cell Carcinoma; Diabetes; Bladder Cancer; Bone and Joint Cancer; Penis Cancer; Anal Cancer; Cancer; Renal Cancer

  12. Supportive care needs of Iranian cancer patients

    Directory of Open Access Journals (Sweden)

    Azad Rahmani

    2014-01-01

    Full Text Available Background: A supportive needs assessment is an essential component of any care program. There is no research evidence regarding the supportive care needs of cancer patients in Iran or other Middle Eastern countries. Aims: The aim of this study was to determine the supportive care needs of Iranian cancer patients. Materials and Methods: This descriptive study was conducted in a referral medical center in the northwest of Iran. A total of 274 cancer patients completed the Supportive Care Needs Survey (SCNS-59. Descriptive statistics were used for data analysis. Results: In 18 items of the SCNS, more than 50% of the participants reported that their needs were unmet. Most frequently, unmet needs were related to the health system, information, physical, and daily living domains, and most met needs were related to sexuality, patient care, and support domains. Conclusions: Iranian cancer patients experience many unmet needs and there is an urgent need for establishing additional supportive care services in Iran.

  13. Depression in cancer patients: a critical review

    Directory of Open Access Journals (Sweden)

    Pasquini Massimo

    2007-02-01

    Full Text Available Abstract Cancer patients experience several stressors and emotional upheavals. Fear of death, interruption of life plans, changes in body image and self-esteem, changes in social role and lifestyle are all important issues to be faced. Moreover, Depressive Disorders may impact the course of the disease and compliance. The cost and prevalence, the impairment caused, and the diagnostic and therapeutic uncertainty surrounding depressive symptoms among cancer patients make these conditions a priority for research. In this article we discuss recent data, focusing on detection of Depressive Disorders, biological correlates, treatments and unmet needs of depressed cancer patients.

  14. [Touching cancer: shiatsu as complementary treatment to support cancer patients].

    Science.gov (United States)

    Argash, Oz; Caspi, Opher

    2008-01-01

    In recent years there has been an increase in the interest of cancer patients in receiving complementary medicine therapies as supportive measures to cure the disease. In response, medical units that combine conventional and complementary medicine (integrative medicine) have been established in leading cancer centers worldwide. In Israel, a special integrative medicine unit that combines mind-body, Chinese medicine, nutrition, herbs, supplements, and manual therapies (such as shiatsu) before, during and after conventional anti-cancer therapies has been established as an integral part of the Davidoff Comprehensive Cancer Center in 2006. Shiatsu represents a group of manual therapeutic techniques, including acupressure. Shiatsu offers cancer patients a non-pharmacologic method to relieve symptoms and improve quality of life throughout the course of illness. Research indicates that acupressure is relatively effective and safe for common cancer-related symptoms such as nausea, vomiting and insomnia. In our experience, shiatsu is also relatively effective and safe for other common symptoms such as fatigue, muscular pain and body image dissatisfaction. Yet, insufficient evidence exists to delineate the best means by which shiatsu and other manual therapies could or should be integrated into routine cancer care. The purpose of the present paper is to describe what is currently known about this topic in order to support decision-making that is based on facts, rather than on myths and misconceptions. We call for more research that examines the effectiveness and safety of shiatsu and other manual therapies in the care of cancer patients.

  15. Chrysin and its emerging role in cancer drug resistance.

    Science.gov (United States)

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Gogoi, Ranadeep

    2015-07-05

    This letter illustrates the significant chemosensitizing effects of chrysin to resistance cancer cells and refers to the article on "Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53" by Li et al., published in your journal recently. Recent studies have demonstrated that chrysin is able to sensitize or kill cancer cells which are resistant to chemotherapeutic drugs such as cisplatin, doxorubicin and adriamycin. Owing to its potential anti-cancer effects and devoid of toxicity to non-transformed cells, further research is required to completely explore its chemosensitizing effects in other cancers and also assess and evaluate its safety, before going for possible human application.

  16. Nanodrug Delivery in Reversing Multidrug Resistance in Cancer Cells

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    Sonali eKapse-Mistry

    2014-07-01

    Full Text Available Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance(MDR which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp, multidrug resistance-associated proteins(MRP1, MRP2 and breast cancer resistance protein(BCRP. Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective and promising platforms for treatment of drug resistant cancer cells. Nanocarriers have potential to improve drug therapeutic index, ability for multifunctionality, divert ABC-transporter mediated drug efflux mechanism and selective targeting to tumor cells, cancer stem cells, tumor initiating cells or cancer microenvironment. Selective nanocarrier targeting to tumor overcomes dose-limiting side effects, lack of selectivity, tissue toxicity, limited drug access to tumor tissues, high drug doses and emergence of multiple drug resistance with conventional or combination chemotherapy. Current review highlights various nanodrug delivery systems to overcome mechanism of MDR by neutralizing, evading or exploiting the drug efflux pumps and those independent of drug efflux pump mechanism by silencing Bcl-2 and HIF1 gene expressions by siRNA and miRNA, modulating ceramide levels and targeting NF-B. Theragnostics combining a cytotoxic agent, targeting moiety, chemosensitizing agent and diagnostic imaging aid are highlighted as effective and innovative systems for tumor localization and overcoming MDR. Physical approaches such as combination of drug with thermal/ultrasound/photodynamic therapies to overcome MDR are focused. The review focuses on newer drug delivery systems developed to overcome

  17. Re-recognition of treatments in patients of non-small cell lung cancer harboring EGFR-TKI resistance%非小细胞肺癌EGFR-TKI耐药治疗策略再认识∗

    Institute of Scientific and Technical Information of China (English)

    何圆(综述); 尤长宣(审校)

    2015-01-01

    Globally, lung cancer is the leading cause of cancer⁃related death with high morbidity, mortality and poor prognosis. The epidermal growth factor receptor⁃tyrosine kinase inhibitor( EGFR⁃TKI) , a means of molecularly targeted therapy, offers a novel ap⁃proach for the treatment of patients with NSCLC harboring EGFR mutation effectively. However, the problem of EGFR⁃TKI resistance ex⁃ists inevitably. A number of promising strategies based on different mechanisms have now been evaluated in phaseⅠ/Ⅱtrials. These in⁃clude EGFR⁃TKI discontinuation, EGFR⁃TKI continuing, EGFR⁃TKI+local treatment, EGFR+other molecularly targeted drugs, EGFR⁃TKI+chemotherapy, EGFR⁃TKI rechallenge, chemotherapy, chemotherapy+other molecularly targeted drugs and EGFR⁃TKI+immunother⁃apy. The purpose of this paper will draw a summary on the progress of treatments in patients with NSCLC harboring EGFR⁃TKI resistance.%肺癌是全球范围内首位癌性死亡因素,发病率、死亡率高,预后欠佳。作为一种分子靶向治疗手段,表皮生长因子酪氨酸激酶抑制剂(EGFR⁃TKI)为EGFR突变的非小细胞肺癌(NSCLC)患者提供了一个新的治疗方向,且疗效显著,然而不可避免的是EGFR⁃TKI耐药问题。鉴于Ⅰ/Ⅱ期临床试验结果,目前有关EGFR⁃TKI耐药治疗策略包括:EGFR⁃TKI停药、继续EGFR⁃TKI、EGFR⁃TKI+局部治疗、EGFR⁃TKI+化疗、EGFR+其他分子靶向药物治疗、EGFR⁃TKI再尝试、化疗、化疗+其他分子靶向药物治疗、EGFR⁃TKI+免疫治疗等,前景值得期待。本文就当前NSCLC患者EGFR⁃TKI耐药治疗进展作一综述。

  18. Altered Ca2+-Homeostasis of Cisplatin-Treated and Low Level Resistant Non-Small-Cell and Small-Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kathrin Schrödl

    2009-01-01

    Full Text Available Background: Chemotherapy often leads to encouraging responses in lung cancer. But, in the course of the treatment, resistance to chemotherapy ultimately limits the life expectancy of the patient. We aimed at investigating if treatment with cisplatin alters the intracellular Ca2+-homeostasis of lung cancer cells and how this may be related to cisplatin resistance.

  19. Cystathionine beta-synthase (CBS contributes to advanced ovarian cancer progression and drug resistance.

    Directory of Open Access Journals (Sweden)

    Sanjib Bhattacharyya

    Full Text Available BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA, in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  20. MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    Mei Liu; Xin Zhang; Chen-Fei Hu; Qing Xu; Hong-Xia Zhu; Ning-Zhi Xu

    2014-01-01

    Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.

  1. Gastric cancer patients at high-risk of having synchronous cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Ho Lee; Jae-Gahb Park; Jae-Moon Bae; Ja Seong Bae; Keun Won Ryu; Jong Seok Lee; Sook Ryun Park; Chan Gyoo Kim; Myoung Cheorl Kook; Il Ju Choi; Young Woo Kim

    2006-01-01

    AIM: To identify patients with a high-risk of having a synchronous cancer among gastric cancer patients.METHODS: We retrospectively analyzed the prospective gastric cancer database at the National Cancer Center,Korea from December 2000 to December 2004. The clinicopathological characteristics of patients with synchronous cancers and those of patients without synchronous cancers were compared. Multivariate analysis was performed to identify the risk factors for the presence of a synchronous cancer in gastric cancer patients.RESULTS: 111 of 3291 gastric cancer patients (3.4%)registered in the database had a synchronous cancer.Among these 111 patients, 109 had a single synchronous cancer and 2 patients had two synchronous cancers. The most common form of synchronous cancer was colorectal cancer (42 patients, 37.2%) followed by lung cancer (21 patients, 18.6%). Multivariate analyses revealed that elderly patients with differentiated early gastric cancer have a higher probability of a synchronous cancer.CONCLUSION: Synchronous cancers in gastric cancer patients are not infrequent. The physicians should try to find synchronous cancers in gastric cancer patients,especially in the elderly with a differentiated early gastric cancer.

  2. Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance

    Directory of Open Access Journals (Sweden)

    Tameka A Bailey

    2011-01-01

    Full Text Available The Human Epidermal Growth Factor Receptor 2 (Her2, ErbB2 or Neu is overexpressed in about 20 - 25% of breast cancers and is causally linked to oncogenesis, providing opportunities for targeted therapy. Trastuzumab (Herceptin™, Genentech Inc, San Francisco, CA, a humanized monoclonal antibody against ErbB2, is a successful example of this concept and has vastly improved the response to treatment and overall survival in a majority of ErbB2+ breast cancer patients. However, lack of response in some patients as well as relapse during the course of therapy in others, continue to challenge researchers and clinicians alike towards a better understanding of the fundamental mechanisms of Trastuzumab action and resistance to treatment. The exact in vivo mechanism of action of Trastuzumab remains enigmatic, given its direct effects on the ErbB2 signaling pathway as well as indirect contributions from the immune system, by virtue of the ability of Trastuzumab to elicit Antibody-Dependent Cellular Cytotoxicity. Consequently, multiple mechanisms of resistance have been proposed. We present here a comprehensive review of our current understanding of the mechanisms, both of Trastuzumab action and clinical resistance to Trastuzumab-based therapies. We also review newer strategies (based on ErbB2 receptor biology that are being explored to overcome resistance to Trastuzumab therapy.

  3. New developments in the treatment of castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Roxanne Wadia

    2014-08-01

    Full Text Available In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer (CRPC have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRPC, as well as the new drugs and targets, which have evolved from this basic research.

  4. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Byeong Mo Kim

    2015-11-01

    Full Text Available Ionizing radiation (IR, such as X-rays and gamma (γ-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  5. Breast cancer and possible mechanisms of therapy resistance

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2013-03-01

    Full Text Available Breast cancer represents one of the most common cancers in women and is a major life threatening illness found all over the world. Therapy approaches include irradiation and surgery, with chemotherapy considered an important strategy to treat breast cancer. Platinum based anticancer drugs, such as cisplatin (cis-di-amino-dichloride-platin, CDDP, carboplatin, orthoplatin, etc., have been successfully used in breast cancer therapy because they activate multiple mechanisms to induce apoptosis in tumor cells. Nevertheless, during chemotherapy, drug resistance frequently develops; this impairs the successful treatment of breast cancer and often leads to patients’ decease. While combinations of anticancer drugs used in chemotherapy regimens reduced the occurrence of drug resistance (e.g. doxorubicin + docetaxel, doxorubicin + cyclophosphamide, docetaxel + herceptin + carboplatin the molecular mechanism of those effects are not completely understood. Here we review possible mechanisms related to breast cancer treatment and resistance to current therapies as well as possible new therapeutic targets (e.g. calcium signaling which could be used in the future.

  6. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy.

    Science.gov (United States)

    Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

    2015-11-10

    Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  7. Combined effects of lapatinib and bortezomib in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and activity of bortezomib against lapatinib-resistant breast cancer cells.

    Science.gov (United States)

    Ma, Chuandong; Niu, Xiuqing; Luo, Jianmin; Shao, Zhimin; Shen, Kunwei

    2010-10-01

    Lapatinib and bortezomib are highly active against breast cancer cells. Breast cancer patients who initially respond to lapatinib may eventually manifest acquired resistance to this treatment. Thus, the identification of novel agents that may prevent or delay the development of acquired resistance to lapatinib is critical. In the current study, we show that the combination of lapatinib and bortezomib results in a synergistic growth inhibition in human epidermal receptor 2 (HER2)-overexpressing breast cancer cells and that the combination enhances apoptosis of SK-BR-3 cells. Importantly, we found that the combination of lapatinib plus bortezomib more effectively blocked activation of the HER2 pathway in SK-BR-3 cells, compared with monotherapy. In addition, we established a model of acquired resistance to lapatinib by chronically challenging SK-BR-3 breast cancer cells with increasing concentrations of lapatinib. Here, we showed that bortezomib notably induced apoptosis of lapatinib-resistant SK-BR-3 pools and further inhibited HER2 signaling in the resistant cells. Taken together, the current data indicate a synergistic interaction between lapatinib and bortezomib in HER2-overexpressing breast cancer cells and provide the rationale for the clinical evaluation of these two noncross-resistant targeted therapies. The combination of lapatinib and bortezomib may be a potentially novel approach to prevent or delay the onset of acquired resistance to lapatinib in HER2-overxpressing/estrogen receptor (ER)-negative breast cancers.

  8. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

    NARCIS (Netherlands)

    Eertwegh, A.J. van den; Versluis, J.; Berg, H.P. van den; Santegoets, S.J.; Moorselaar, R.J. van; Sluis, T.M. van der; Gall, H.E.; Harding, T.C.; Jooss, K.; Lowy, I.; Pinedo, H.M.; Scheper, R.J.; Stam, A.G.; Blomberg, B.M. von; Gruijl, T.D. de; Hege, K.; Sacks, N.; Gerritsen, W.R.

    2012-01-01

    BACKGROUND: The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte ant

  9. Utilizing Data from Cancer Patient & Survivor Studies

    Science.gov (United States)

    Utilizing Data from Cancer Patient & Survivor Studies and Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2011 workshop sponsored by the Epidemiology and Genomics Research Program.

  10. Cognitive Behavioral Therapy in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Cem Soylu

    2014-09-01

    Full Text Available Cognitive behavioral therapy is one of the structured but flexible psychosocial interventions that could be applied to patients with cancer. In many studies the positive effects of cognitive behavioral therapy in reducing psychological morbidity and improving the quality of life of cancer patients have been shown. In this article, the contents and techniques of adapted cognitive behavioral therapy for patients with cancer and its effectiveness in commonly seen psychiatric disorders have been reviewed. The aim of this article is to contribute positively to physicians and nurses in Turkey for early detection of psychological distress and referral to the therapist that would clearly increase the quality of life of cancer patients. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 257-270

  11. Overcoming multidrug resistance(MDR) in cancer by nanotechnology

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The emerging nanotechnology-based drug delivery holds tremendous potential to deliver chemotherapeutic drugs for treatment of multidrug resistance(MDR) cancer.This drug delivery system could improve the pharmacokinetic behavior of antitumor drugs,deliver chemotherapeutic drugs to target sites,control release of drugs,and reduce the systemic toxicity of drugs in MDR cancer.This review addresses the use of nanotechnology to overcome MDR classified on the bases of the fundamental mechanisms of MDR and various approaches to deliver drugs for treatment of MDR cancer.

  12. Mechanisms of Resistance to Target Therapies in Non-small Cell Lung Cancer.

    Science.gov (United States)

    Facchinetti, Francesco; Proto, Claudia; Minari, Roberta; Garassino, Marina; Tiseo, Marcello

    2017-03-23

    Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i.e. MET amplification, KRAS mutations); (3) phenotype transformation (to small cell lung cancer, epithelial-mesenchymal transition). These basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. Novel-generation molecules include osimertinib, for EGFR-T790M-positive patients, and new ALK-TKIs. Nevertheless, the possible concomitant presence of multiple resistance mechanisms, as well as their heterogeneity among cells and disease localizations, makes research in this field particularly arduous. In this chapter, available evidence and perspectives concerning precise mechanisms of escape to pharmacological inhibition in oncogene-addicted NSCLC are reported for single targets, including but not limited to EGFR and ALK.

  13. Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer.

    Science.gov (United States)

    Mohd Nafi, Siti Norasikin; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Haider, Syed; Li, Ji-Liang; Bridges, Esther; Capala, Jacek; Ioannis, Roxanis; Harris, Adrian L; Kong, Anthony

    2014-08-15

    The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response. There was also increased nuclear HER4 staining in the tumours from BT474 xenograft mice and human patients treated with trastuzumab. Furthermore, nuclear HER4 predicted poor clinical response to trastuzumab monotherapy in patients undergoing a window study and was shown to be an independent poor prognostic factor in HER2 positive breast cancer. Our data suggest that HER4 plays a key role in relation to trastuzumab resistance in HER2 positive breast cancer. Therefore, our study provides novel findings that HER4 activation, cleavage and nuclear translocation influence trastuzumab sensitivity and resistance in HER2 positive breast cancer. Nuclear HER4 could be a potential prognostic and predictive biomarker and understanding the role of HER4 may provide strategies to overcome trastuzumab resistance in HER2 positive breast cancer.

  14. β-Diketone modified trastuzumab: a next-generation of Herceptin for resistant breast cancer cells?

    Science.gov (United States)

    Lu, Jianguo; Pu, Jun; Lu, Xiaozhao; Fu, Haiyan; Wei, Mengying; Yang, Guodong

    2012-11-01

    Despite the initial efficacy of trastuzumab (commercially named Herceptin), acquired resistance in a majority of patients remains the biggest hurdle in breast cancer therapy. Recently, the Scripps Research Institute developed a method termed "instant immunity", in which antibodies (chemical programmed antibody) are rapidly induced by chemicals like β-diketone. When β-diketone is chemically linked to peptides specifically targeting cancer cells, the instant chemical programmed antibody would clear the cancer cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC). This novel strategy has a super advantage over passive immunization or immunization with recombinant or vectored vaccines because it induces a universal immune response and memory. Theoretically, combination of the cancer cell specific recognition advantage of trastuzumab and cancerous cell clearance of active immunization would be an option for trastuzumab resistant patients, which harbors both the advantages of cancer specific targeting of trastuzumab and active immunization of the "instant immunity", implicating a better clinical outcome. Further studies are needed to verify our hypothesis, which is worth validating.

  15. Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Huber, Marie L; Haynes, Laura; Parker, Chris

    2012-01-01

    Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused....... The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month...... survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two...

  16. Symptom monitoring in treatment of cancer patients

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To examine self-reported symptoms by the patients receiving cancer therapy, and find out the symptoms that should be coped with and managed during the treatment. Methods A pilot study was conducted on self-reported symptoms on 185 patients receiving chemotherapy and/or radiotherapy for different cancers. The Therapy-Related Symptoms Checklist (TRSC) was used. Results Severe symptoms on the TRSC subscales: loss of appetite, feeling sluggish, weight loss, nausea and hair loss, were reported by the p...

  17. The cellular cancer resistance of the SR/CR mouse

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

    2012-01-01

    injection showed formations of immune cells morphologically resembling polymorphonuclear granulocytes and macrophages adjoining the cancer cells. The results point to the potential involvement of innate immune cells in cancer immunology. Our data support migration of polymorphonuclear granulocytes......The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally. The tumor cell targeting and destruction mechanisms have not been identified. By fluorescence......-activated cell sorting analysis, the immune response of SR/CR mice after intraperitoneal injection of cancer cells was investigated and compared with parent strain mice. A massive influx of leukocytes into the peritoneal cavity was found. A large fraction of these leukocytes were polymorphonuclear granulocytes...

  18. HIF2α contributes to antiestrogen resistance via positive bilateral crosstalk with EGFR in breast cancer cells

    DEFF Research Database (Denmark)

    Alam, Muhammad Wasi; Persson, Camilla Ulrika; Reinbothe, Susann

    2016-01-01

    The majority of breast cancers express estrogen receptor α (ERα), and most patients with ERα-positive breast cancer benefit from antiestrogen therapy. The ERα-modulator tamoxifen and ERα-downregulator fulvestrant are commonly employed antiestrogens. Antiestrogen resistance remains a clinical...... challenge, with few effective treatments available for patients with antiestrogen-resistant breast cancer. Hypoxia, which is intrinsic to most tumors, promotes aggressive disease, with the hypoxia-inducible transcription factors HIF1 and HIF2 regulating cellular responses to hypoxia. Here, we show...... that the ERα-expressing breast cancer cells MCF-7, CAMA-1, and T47D are less sensitive to antiestrogens when hypoxic. Furthermore, protein and mRNA levels of HIF2α/HIF2A were increased in a panel of antiestrogen-resistant cells, and antiestrogen-exposure further increased HIF2α expression. Ectopic expression...

  19. Ovarian stimulation in patients with breast cancer.

    Science.gov (United States)

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  20. Cancer-drug induced insulin resistance : Innocent bystander or unusual suspect

    NARCIS (Netherlands)

    Ariaans, G.; de Jong, S.; Gietema, J. A.; Lefrandt, J. D.; de Vries, E. G. E.; Jalving, M.

    2015-01-01

    Epidemiological and experimental evidence strongly suggests an association between type 2 diabetes mellitus and cancer. Insulin resistance, causing hyperinsulinaemia and eventually hyperglycaemia, appears to increase cancer incidence and disease progression. In addition, insulin resistance seems to

  1. Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

    DEFF Research Database (Denmark)

    Joshi, Tejal; Elias, Daniel; Stenvang, Jan

    2016-01-01

    Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of mi...... and siRNAmediated gene knockdown, we showed that both SNAI2 and FYN significantly affect the growth of TamR cell lines. Finally, we show that a combination of 2 miRNAs (miR-190b and miR-516a-5p) exhibiting altered expression in TamR cell lines were predictive of treatment outcome in a cohort of ER......+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer....

  2. Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2.

    Science.gov (United States)

    Han, Zheng-Xiang; Wang, Hong-Mei; Jiang, Guan; Du, Xiu-Ping; Gao, Xiang-Yang; Pei, Dong-Sheng

    2013-06-01

    Lung cancer is the leading cause of death from malignancy in people and over 85% of these patients eventually die from disseminated disease. Paclitaxel (TAX) is widely used as an antimicrotubule agent for the treatment of lung cancer. Unfortunately, the resistance to this antimicrotubule agent occurs frequently. Stathmin (STMN1) is a ubiquitous microtubule destabilizing protein linked to cancer and cell health and its expression level often correlates with cancer stage progression and prognosis for survival. Overexpression of the antiapoptotic protein Bcl-2 has been shown to prolong drug-induced growth arrest, potentially inducing resistance. In this study, we used a short hairpin RNA (shRNA) approach to evaluate the effect of STMN1 and Bcl-2 downregulation in the sensitivity to TAX in lung cancer cells. We achieved significant downregulation of STMN1 and Bcl-2 mRNA and protein expression by a combination of double shRNA treatment strategy. Our experimental data showed that inhibition of STMN1 and Bcl-2 expression with RNA interference can sensitize lung cancer cells to TAX. These findings suggest a novel approach to improve the efficacy of certain antimicrotubule agents against lung cancer by regulating the function of STMN1 and Bcl-2.

  3. Insulin resistance, its consequences for the clinical course of the disease, and possibilities of correction in endometrial cancer

    NARCIS (Netherlands)

    Berstein, LM; Kvatchevskaya, JO; Poroshina, TE; Kovalenko, IG

    2004-01-01

    Objectives: To study the frequency of insulin resistance (IR) in endometrial cancer patients, its relation to the clinical course of the disease and DNA damage, and to evaluate possible approaches to the pharmacological correction of IR in the patients studied. Methods: The signs of insulin resistan

  4. Identification of resistance mechanisms in erlotinib-resistant subclones of the non-small cell lung cancer cell line HCC827 by exome sequencing

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Alcaraz, Nicolas; Lund, Rikke Raaen

    Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as 70% of patients show significant tumor regression upon treatment (Santarpia et. al., 2013). However, all patients relapse due to development of acquired resistance, which...... mutations in erlotinib-resistant subclones of the NSCLC cell line, HCC827. Materials & Methods: We established 3 erlotinib-resistant subclones (resistant to 10, 20, 30 µM erlotinib, respectively). DNA libraries of each subclone and the parental HCC827 cell line were prepared in biological duplicates using...... exhibited a significant difference in viability over a time course of 25 days when treated with erlotinib. Importantly, the resistant clones did not acquire the T790M or other EGFR or KRAS mutations, potentiating the identification of novel resistance mechanisms in these clones. For the sensitive and the 3...

  5. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mecha

  6. Modulation of breast cancer resistance protein mediated atypical multidrug resistance using RNA interference delivered by adenovirus

    Institute of Scientific and Technical Information of China (English)

    LI Wen-tong; ZHOU Geng-yin; WANG Chun-ling; GUO Cheng-hao; SONG Xian-rang; CHI Wei-ling

    2005-01-01

    @@ Clinical multidrug resistance (MDR) of malignancies to many antineoplastic agents is the major obstacle in the successful treatment of cancer. The emergence of breast cancer resistance protein (BCRP), a member of the adenosine triphosphate (ATP) binding cassette (ABC) transporter family, has necessitated the development of antagonists. To overcome the BCRP-mediated atypical MDR, RNA interference (RNAi) delivered by adenovirus targeting BCRP mRNA was used to inhibit the atypical MDR expression by infecting MCF-7/MX100 cell lines with constructed RNAi adenovirus.

  7. Oncolytic Virotherapy Targeting Lung Cancer Drug Resistance

    Science.gov (United States)

    2013-08-01

    peptides that bind to and inactivate small molecules such as cisplatin; (3) upregulate DNA repair enzymes that reverse therapy-induced DNA lesions; and...but multidrug-resistant tumor cells still possess clonal potential and after a short period of remission expand further and acquire metastatic

  8. Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA.

    Science.gov (United States)

    Hayes, Erin L; Lewis-Wambi, Joan S

    2015-01-01

    Endocrine therapies such as tamoxifen and aromatase inhibitors are the standard treatment options for estrogen receptor-positive breast cancer patients. However, resistance to these agents has become a major clinical obstacle. Potential mechanisms of resistance to endocrine therapies have been identified, often involving enhanced growth factor signaling and changes in the expression or action of the estrogen receptor, but few studies have addressed the role of noncoding RNA (ncRNA). Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). miRNAs are small RNA molecules that regulate gene expression via translational inhibition or degradation of mRNA transcripts, while lncRNAs are larger RNA molecules that have been shown to play a role in multiple cellular maintenance functions such as protein scaffolding, chromatin looping, and regulation of mRNA stability. Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. This review serves as an overview of the roles of miRNA and lncRNA in breast cancer progression and the development of endocrine resistance. Ideally, future experiments in the field should include identification of ncRNAs that could be potential therapeutic targets in endocrine-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for endocrine-resistant breast cancer patients.

  9. Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression

    Institute of Scientific and Technical Information of China (English)

    Takeo Nakanishi; Douglas D. Ross

    2012-01-01

    Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) is an ATP-binding cassette (ABC) transporter identified as a molecular cause of multidrug resistance (MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism; it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal (stemness),and invasiveness (aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α, estrogen receptor, and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modificationare likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will

  10. Circulating gangliosides of breast-cancer patients.

    Science.gov (United States)

    Wiesner, D A; Sweeley, C C

    1995-01-27

    Gangliosides were isolated from the sera of recently diagnosed breast-cancer patients and from individuals who were apparently free of disease. Quantificative and qualitative analyses were carried out by 2-dimensional high-performance thin-layer chromatography and gas chromatography. The locations of isolated gangliosides on thin-layer chromatograms were determined by visualization with resorcinol, and each spot was quantified by digital image densitometry. The ganglioside profiles of cancer patients were compared to those of the control group, revealing a significant increase in total lipid-bound sialic acid and a specific increase in polysialogangliosides in the patients with breast cancer. Furthermore, an increase was noted in the ratio of gangliosides of the b-series biosynthetic pathway over those of the a-series in the cancer sera, as compared to the controls. Gas chromatographic analysis of the peracetylated methanolysis mixtures derived from the total ganglioside fraction of cancer patients supported the HPTLC data, with an increase in total sialic acid, galactose, and sphingosine residues. No unusual gangliosides were found in the mixture from breast-cancer patients.

  11. Mesenchymal Stem Cell-Induced Doxorubicin Resistance in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Dar-Ren Chen

    2014-01-01

    Full Text Available Triple negative breast cancer (TNBC is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs, tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM, noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients.

  12. Mesenchymal stem cell-induced doxorubicin resistance in triple negative breast cancer.

    Science.gov (United States)

    Chen, Dar-Ren; Lu, Dah-Yuu; Lin, Hui-Yi; Yeh, Wei-Lan

    2014-01-01

    Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC) transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients.

  13. Contemporary agents in the management of metastatic castration-resistant prostate cancer

    Science.gov (United States)

    Kapoor, Anil; Wu, Christopher; Shayegan, Bobby; Rybak, Adrian P.

    2016-01-01

    Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC. Cabazitaxel, abiraterone acetate, and enzalutamide are three agents recently approved for the treatment of mCRPC, having shown overall survival benefit in patients previously treated with docetaxel, while both abiraterone acetate and enzalutamide have also shown promise in the pre-docetaxel setting. Sipuleucel-T has shown overall survival benefit in asymptomatic mCRPC, while radium-223 provides survival benefit to patients with mCRPC who are symptomatic from their skeletal metastases in both docetaxel-naïve patients and post-docetaxel patients. Denosumab, an anti-RANKL antibody, has been approved for the prevention of skeletal-related events in patients with prostate cancer bone metastases. This review examines the phase 3 trials supporting the use of theses novel agents in the treatment of mCRPC. While these agents provide incremental increases in patient survival, further study to determine the best choice, combination, and/or sequencing of administration is still necessary. PMID:28096932

  14. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  15. Emerging targeted therapies for castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo eAdamo

    2012-05-01

    Full Text Available Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC. Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone and denosumab have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel hormone-therapeutic, intracellular molecular pathways inhibiting, anti-angiogenic, bone microenvironment targeting and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan. Optimal timing, right combination and/or sequencing of emerging therapies as well as use of more sensitive biological markers to individualize therapies for CRPC remain challenging and studies to investigate these aspects are needed.

  16. Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Rosenberg JE

    2012-01-01

    Full Text Available Yasser Rehman1, Jonathan E Rosenberg21Division of Hospital Medicine, UMass Memorial Healthcare, Worcester, MA, USA; 2Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC, which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17. This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.Keywords: CRPC, abiraterone, CYP17, inhibitors, androgens, castration resistant prostate cancer

  17. Reversal of Multidrug Resistance in Breast Cancer

    Science.gov (United States)

    1994-08-23

    cellular resistance to multiple therapeutic agents such as anthracyclines, vinca alkaloids , epipodophyllotoxins, taxol, and actinomycin-D. MDR1 gene...Sci USA 84:3004.1987. Zacher, V., Thomas, R.A., and Goustin, A.S. Absolute quantification of target DNA: a simple competitive PCR for efficient...target appears to be the microtubular apparatus, but unlike vinca alkaloids or epipodophyllotoxin, Paclitaxel actually promotes microtubular assemblyin

  18. Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.

    Science.gov (United States)

    Bhirde, Ashwinkumar A; Chikkaveeraiah, Bhaskara V; Srivatsan, Avinash; Niu, Gang; Jin, Albert J; Kapoor, Ankur; Wang, Zhe; Patel, Sachin; Patel, Vyomesh; Gorbach, Alexander M; Leapman, Richard D; Gutkind, J Silvio; Hight Walker, Angela R; Chen, Xiaoyuan

    2014-05-27

    Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm(2), 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.

  19. Multidisciplinary approach for patients with esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Victoria M Villaflor; Marco E Allaix; Bruce Minsky; Fernando A Herbella; Marco G Patti

    2012-01-01

    Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced.There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease.Often,esophageal cancer is not diagnosed until patients present with dysphagia,odynophagia,anemia or weight loss.When symptoms occur,the stage is often stage Ⅲ or greater.Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection.The treatment of patients who have locally advanced esophageal cancer is more complex and controversial.Despite multiple trials,treatment recommendations are still unclear due to conflicting data.Sadly,much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically.Additionally,studies have been underpowered or stopped early due to poor accrual.In the United States,concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient.Patients who have metastatic disease are treated palliatively.The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer,and to review the literature which guides our treatment recommendations.

  20. Positive feelings among terminally ill cancer patients.

    Science.gov (United States)

    Van der Lee, M L; Swarte, N B; Van der Bom, J G; Van den Bout, J; Heintz, A P M

    2006-03-01

    For a realistic perspective on what it is like to have cancer and be in the last months of life, it is necessary to also study the positive feelings people may still experience. We set out to describe positive feelings experienced by terminally ill patients. The Depression Adjective Checklist was completed by 96 cancer patients with an estimated life expectancy of less than 3 months. On average patients endorsed 30% (3.6/12) of the positive mood items, and 25% (5.4/22) of the negative mood items. The larger part of terminally ill cancer patients with an estimated life expectancy of less than 3 months reported one or more positive mood states. A positive mood state such as 'being interested' was endorsed by more than half (65%) of the patients, other positive feelings were endorsed by a substantial proportion of patients, for example: 38% of patients endorsed feeling 'jovial' and 35% reported being 'optimistic'. Although having incurable cancer often leads to feelings of depression, mood is variable and many patients experience at least some positive feelings.

  1. Identification of Bone-Derived Factors Conferring De Novo Therapeutic Resistance in Metastatic Prostate Cancer.

    Science.gov (United States)

    Lee, Yu-Chen; Lin, Song-Chang; Yu, Guoyu; Cheng, Chien-Jui; Liu, Bin; Liu, Hsuan-Chen; Hawke, David H; Parikh, Nila U; Varkaris, Andreas; Corn, Paul; Logothetis, Christopher; Satcher, Robert L; Yu-Lee, Li-Yuan; Gallick, Gary E; Lin, Sue-Hwa

    2015-11-15

    Resistance to currently available targeted therapies significantly hampers the survival of patients with prostate cancer with bone metastasis. Here we demonstrate an important resistance mechanism initiated from tumor-induced bone. Studies using an osteogenic patient-derived xenograft, MDA-PCa-118b, revealed that tumor cells resistant to cabozantinib, a Met and VEGFR-2 inhibitor, reside in a "resistance niche" adjacent to prostate cancer-induced bone. We performed secretome analysis of the conditioned medium from tumor-induced bone to identify proteins (termed "osteocrines") found within this resistance niche. In accordance with previous reports demonstrating that activation of integrin signaling pathways confers therapeutic resistance, 27 of the 90 osteocrines identified were integrin ligands. We found that following cabozantinib treatment, only tumor cells positioned adjacent to the newly formed woven bone remained viable and expressed high levels of pFAK-Y397 and pTalin-S425, mediators of integrin signaling. Accordingly, treatment of C4-2B4 cells with integrin ligands resulted in increased pFAK-Y397 expression and cell survival, whereas targeting integrins with FAK inhibitors PF-562271 or defactinib inhibited FAK phosphorylation and reduced the survival of PC3-mm2 cells. Moreover, treatment of MDA-PCa-118b tumors with PF-562271 led to decreased tumor growth, irrespective of initial tumor size. Finally, we show that upon treatment cessation, the combination of PF-562271 and cabozantinib delayed tumor recurrence in contrast to cabozantinib treatment alone. Our studies suggest that identifying paracrine de novo resistance mechanisms may significantly contribute to the generation of a broader set of potent therapeutic tools that act combinatorially to inhibit metastatic prostate cancer.

  2. 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.

  3. Understanding taste dysfunction in patients with cancer.

    Science.gov (United States)

    McLaughlin, Laura; Mahon, Suzanne M

    2012-04-01

    Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.

  4. Myofacial trigger points in advanced cancer patients

    Directory of Open Access Journals (Sweden)

    Hideaki Hasuo

    2016-01-01

    Full Text Available Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation.We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points.

  5. Fertility preservation in young cancer patients

    Directory of Open Access Journals (Sweden)

    Ariel Revel

    2010-01-01

    Full Text Available As a result of advances in treatment, almost 80% of children and adolescents who receive a diagnosis of cancer become long-term survivors. The increased survival rate of children and adolescents with cancer has resulted in a major interest in the long-term effects of cancer treatment on the possibility for future fertility. Currently established methods for the preservation of fertility are available only for pubertal males and females. Pubertal male cancer patients should be encouraged to freeze numerous sperm samples even when sperm count and motility are poor. In these cases, intracytoplasmic sperm injection is a powerful technique compared with intrauterine insemination since thawed sperm samples with poor parameters can produce relatively high fertilization rates resulting in normal pregnancies and deliveries. Married pubertal women should be proposed ovulation induction, follicular aspiration, and fertilization with husband sperm. Single women could benefit from vitrification of oocytes. This requires a delay of about 3 weeks in the commencement of chemotherapy to enable follicular growth. Fertility preservation for prepubertal patients is more of a problem. Young girls could be offered cryopreservation of gametes in the gonadal tissue. Cryopreservation of testicular tissue was suggested for fertility preservation for young boys, but this method is totally experimental and not currently offered. Discussing future fertility is part of the consultation of young female and male patients facing potentially gonadotoxic cancer therapy. It is the role of reproductive specialists to create various options in their laboratory to preserve fertility potential of cancer patients.

  6. [Metabolico-nutritional changes in the cancer patient].

    Science.gov (United States)

    Rossi Fanelli, F; Cangiano, C; Muscaritoli, M; Cascino, A

    1989-09-01

    The severe impairment of the nutritional state, which usually accompanies malignant diseases, heavily contributes to the high morbidity and mortality rates observed in cancer patients. Nevertheless, the utility of an artificial energy supply to these patients is still controversial because the nutrients given to replete the host may also stimulate tumor growth. Consequently, a correct nutritional approach for cancer patients should be based upon a well-defined understanding of tumor as well as host-metabolic needs. In this regard, the most typical metabolic abnormalities observed in cancer patients and experimental animals are examined. Specific modifications of the plasma levels of different groups of amino acids--including glucogenic, aromatic, sulphur-containing and branched-chain amino acids--have been observed in cancer patients independently of the their degree of malnutrition, glucose tolerance and tumor diffusion. This may reflect a series of specific modifications induced by the neoplastic tissue on host's protein turnover. Little information is available regarding the protein metabolism in the neoplastic tissue. A number of attempts have been made to reduce tumor growth by withholding single amino acids considered essential to the tumor; nevertheless, the results obtained are still controversial. The two major abnormalities of carbohydrate metabolism observed in cancer patients are an increased glucose turnover and an impaired glucose tissue disposal. The former seems to be due to an increased glucogenesis, whereas the latter may be attributed to an insulin resistance in contrast to the high anaerobic glucose utilization observed in the neoplastic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?

    Science.gov (United States)

    Mita, Alain C; Figlin, Robert; Mita, Monica M

    2012-12-15

    The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support.

  8. Engagement of Patients With Advanced Cancer

    Science.gov (United States)

    2016-11-15

    End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

  9. TFPI1 mediates resistance to doxorubicin in breast cancer cells by inducing a hypoxic-like response.

    Directory of Open Access Journals (Sweden)

    Gerald F Davies

    Full Text Available Thrombin and hypoxia are important players in breast cancer progression. Breast cancers often develop drug resistance, but mechanisms linking thrombin and hypoxia to drug resistance remain unresolved. Our studies using Doxorubicin (DOX resistant MCF7 breast cancer cells reveals a mechanism linking DOX exposure with hypoxic induction of DOX resistance. Global expression changes between parental and DOX resistant MCF7 cells were examined. Westerns, Northerns and immunocytochemistry were used to validate drug resistance and differentially expressed genes. A cluster of genes involved in the anticoagulation pathway, with Tissue Factor Pathway Inhibitor 1 (TFPI1 the top hit, was identified. Plasmids overexpressing TFPI1 were utilized, and 1% O2 was used to test the effects of hypoxia on drug resistance. Lastly, microarray datasets from patients with drug resistant breast tumors were interrogated for TFPI1 expression levels. TFPI1 protein levels were found elevated in 3 additional DOX resistant cells lines, from humans and rats, indicating evolutionarily conservation of the effect. Elevated TFPI1 in DOX resistant cells was active, as thrombin protein levels were coincidentally low. We observed elevated HIF1α protein in DOX resistant cells, and in cells with forced expression of TFPI1, suggesting TFPI1 induces HIF1α. TFPI1 also induced c-MYC, c-SRC, and HDAC2 protein, as well as DOX resistance in parental cells. Growth of cells in 1% O2 induced elevated HIF1α, BCRP and MDR-1 protein, and these cells were resistant to DOX. Our in vitro results were consistent with in vivo patient datasets, as tumors harboring increased BCRP and MDR-1 expression also had increased TFPI1 expression. Our observations are clinically relevant indicating that DOX treatment induces an anticoagulation cascade, leading to inhibition of thrombin and the expression of HIF1α. This in turn activates a pathway leading to drug resistance.

  10. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian

    2013-01-01

    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  11. Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss.

    Science.gov (United States)

    Beauchamp, Ellen M; Woods, Brittany A; Dulak, Austin M; Tan, Li; Xu, Chunxiao; Gray, Nathanael S; Bass, Adam J; Wong, Kwok-kin; Meyerson, Matthew; Hammerman, Peter S

    2014-02-01

    The treatment of non-small cell lung cancer has evolved dramatically over the past decade with the adoption of widespread use of effective targeted therapies in patients with distinct molecular alterations. In lung squamous cell carcinoma (lung SqCC), recent studies have suggested that DDR2 mutations are a biomarker for therapeutic response to dasatinib and clinical trials are underway testing this hypothesis. Although targeted therapeutics are typically quite effective as initial therapy for patients with lung cancer, nearly all patients develop resistance with long-term exposure to targeted drugs. Here, we use DDR2-dependent lung cancer cell lines to model acquired resistance to dasatinib therapy. We perform targeted exome sequencing to identify two distinct mechanisms of acquired resistance: acquisition of the T654I gatekeeper mutation in DDR2 and loss of NF1. We show that NF1 loss activates a bypass pathway, which confers ERK dependency downstream of RAS activation. These results indicate that acquired resistance to dasatinib can occur via both second-site mutations in DDR2 and by activation of bypass pathways. These data may help to anticipate mechanisms of resistance that may be identified in upcoming clinical trials of anti-DDR2 therapy in lung cancer and suggest strategies to overcome resistance.

  12. [Multidisciplinary therapy for 984 cancer patients--hyperthermic immunotherapy].

    Science.gov (United States)

    Takeda, Tsutomu; Miyazawa, Kenki; Takeda, Takashi; Takeda, Hiroko; Takeda, Yutaka

    2010-11-01

    We treated 984 advanced or recurrent cancer patients with hyperthermia or immunotherapy (2005/7-2009/12). We have 137 clinical benefit cases (CR, PR and long SD) including 22 complete response (CR) cases. Effective rates of immunotherapy increased from 9.8% to 17.8% using hyperthermia. In the cases of ovarian cancer, head and neck cancer, lung cancer, prostatic cancer, gastric cancer, thyroid cancer and breast cancer, all confirmed high effective rates with hyperthermic immunotherapy.

  13. Patient Delay in Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Pedersen, Anette Fischer; Hansen, Rikke P; Vedsted, Peter

    2013-01-01

    , at patienter med kolorektal¬kræft, som har oplevet blødning fra endetarmen, har længere forsinkelser i forløbet (39 dage) end patienter, som ikke har haft dette symptom (15 dage). Tidligere studier har tolket det som et tegn på, at patienter med rektal blødning regner med, at blødningen skyldes godartede...... lidelser. Dette studie finder som noget nyt, at mange patienter med rektal blødning har tænkt mere over kræft i perioden op til første lægebesøg end patienter uden dette symptom. En forkert tolkning af symptomet er altså ikke den eneste forklaring på forsinkelserne i forløbet for denne patientgruppe....... Fundene i studiet åbner for den mulighed, at forsinkelserne hos nogle patienter kan skyldes bekymring for, hvad lægen vil finde, og at de derfor tøver med at konsultere lægen. Denne tøven kan hænge sammen med følelses¬mæssige barrierer, fx at patienten er flov over symptomerne eller frygter forestående...

  14. How Exercise Can Benefit Patients With Cancer.

    Science.gov (United States)

    Musanti, Rita

    2016-12-01

    Thirty years ago, the first article on exercise for patients with cancer appeared in the cancer research literature. The time from that first article to the present has included oncology nurses taking the lead in investigations related to exercise and cancer-related symptoms, most notably cancer-related fatigue (CRF). The Oncology Nursing Society (ONS) has been instrumental in publishing much of the research on exercise and cancer and continues in that tradition by issuing this supplement to the Clinical Journal of Oncology Nursing. In addition, ONS has facilitated the translation of research findings to practicing oncology nurses by convening meetings, participating in expert opinion consensus groups, and disseminating evidence through Putting Evidence Into Practice resources.

  15. LC-MS Based Sphingolipidomic Study on A2780 Human Ovarian Cancer Cell Line and its Taxol-resistant Strain

    Science.gov (United States)

    Huang, Hao; Tong, Tian-Tian; Yau, Lee-Fong; Chen, Cheng-Yu; Mi, Jia-Ning; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-01-01

    Drug resistance elicited by cancer cells continue to cause huge problems world-wide, for example, tens of thousands of patients are suffering from taxol-resistant human ovarian cancer. However, its biochemical mechanisms remain unclear. Sphingolipid metabolic dysregulation has been increasingly regarded as one of the drug-resistant mechanisms for various cancers, which in turn provides potential targets for overcoming the resistance. In the current study, a well-established LC-MS based sphingolipidomic approach was applied to investigate the sphingolipid metabolism of A2780 and taxol-resistant A2780 (A2780T) human ovarian cancer cell lines. 102 sphingolipids (SPLs) were identified based on accurate mass and characteristic fragment ions, among which 12 species have not been reported previously. 89 were further quantitatively analyzed by using multiple reaction monitoring technique. Multivariate analysis revealed that the levels of 52 sphingolipids significantly altered in A2780T cells comparing to those of A2780 cells. These alterations revealed an overall increase of sphingomyelin levels and significant decrease of ceramides, hexosylceramides and lactosylceramides, which concomitantly indicated a deviated SPL metabolism in A2780T. This is the most comprehensive sphingolipidomic analysis of A2780 and A2780T, which investigated significantly changed sphingolipid profile in taxol-resistant cancer cells. The aberrant sphingolipid metabolism in A2780T could be one of the mechanisms of taxol-resistance. PMID:27703266

  16. Increased STAT1 signaling in endocrine-resistant breast cancer.

    Directory of Open Access Journals (Sweden)

    Rui Huang

    Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

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

    DEFF Research Database (Denmark)

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

    , and head and neck cancer. No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. Methods: Eligibility criteria are confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end...... to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue...

  18. Quantitative proteomics as a tool to identify resistance mechanisms in erlotinib-resistant subclones of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine

    Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as approximately 70% of patients show significant tumor regression when treated (Santarpia et. al., 2013). However, all patients relapse due to development of acquired resistance......, which in 43-50% of cases are caused by a secondary mutation (T790M) in EGFR. Importantly, a majority of resistance cases are still unexplained (Lin & Bivona, 2012). Our aim is to identify novel resistance mechanisms – and potentially new drug targets - in erlotinib-resistant subclones of the NSCLC cell...... of erlotinib, and in biological triplicates on a Q-Exactive mass spectrometer. Only proteins identified with minimum 2 unique peptides and in minimum 2 of 3 replicates were accepted. Results: Importantly, the resistant clones did not acquire the T790M or other EGFR or KRAS mutations, potentiating...

  19. Update on options for treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2010-03-01

    Full Text Available Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC, the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16 in CRPC, several newer cytotoxic drugs (epothilones, satraplatin, targeted agents (abiraterone, MDV3100 and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cells

  20. Cancer epigenetics: a perspective on the role of DNA methylation in acquired endocrine resistance

    Institute of Scientific and Technical Information of China (English)

    Michael P. Trimarchi; Mary Mouangsavanh; Tim Hui-Ming Huang

    2011-01-01

    Epigenetic mechanisms,including DNA methylation,are responsible for determining and maintaining cell fate,stably differentiating the various tissues in our bodies.Increasing evidence shows that DNA methylation plays a significant role in cancer,from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis.Recent studies also suggest a role for DNA methylation in drug resistance.This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance,with a focus on breast cancer.In addition,we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance.Hormone ablation is the therapy of choice for hormone-sensitive breast tumors,yet as many as 40% of patients inevitably relapse,and these hormone refractory tumors often have a poor prognosis.Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment.Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells.Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood,and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts.Going forward,DNA methylome profiling will become increasingly central to epigenetic research,heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible.

  1. Mental health of patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Τogas Κ.

    2016-07-01

    Full Text Available Background: Lung cancer is a very common type of cancer. The psychological reactions of these patients haven't been studied yet. Aim: The examination of the mental health of lung cancer patients. Methods: A bibliographical review of relevant articles was conducted at the electronic data bases of Pubmed, Pcych Info and Scholar Google by key-words. The quest included researches and reviews which have been published in Greek and English language between 1990- 2013. Results: Lung cancer is the second most common type of cancer and the main cause of death from cancer. The psychological reaction depends on the symptomatology, the co- morbidity, the cell type, the physical and social functionality, the therapy. The most important needs of the patients are the emotional ones as well as the need of information. The patients mention the highest levels of psychological discontent and stigmatization in comparison to other types of cancer. They show lots of psychological disorders, with depression to be the most common (11%- 44%. Very few researches have examine the confrontation strategies. Health professionals are the main source of information for the patients and the help that they provide is correlated with all the dimensions of the quality of life (except of the social ones. Oncologists don't recognize in a satisfying degree the patients with distress. Most of the patients use in a limited degree the mental health services. Important determinants of survival are the emotional distress, depression and the coping strategies. Different methods of psychotherapy can be applied in order to diminish the psychological distress. The behavioural interventions decrease nausea and sickness and the disturbance of pain and anxiety. The palliative and supportive care have to be applied as sooner as possible. Conclusion: The psychological reaction in lung cancer is complicated. There is need for appliance of psychotherapeutic interventions at the patients, in order to

  2. Palliative care in cancer: managing patients' expectations.

    Science.gov (United States)

    Ghandourh, Wsam A

    2016-12-01

    Advanced cancer patients commonly have misunderstandings about the intentions of treatment and their overall prognosis. Several studies have shown that large numbers of patients receiving palliative radiation or chemotherapy hold unrealistic hopes of their cancer being cured by such therapies, which can affect their ability to make well-informed decisions about treatment options. This review aimed to explore this discrepancy between patients' and physicians' expectations by investigating three primary issues: (1) the factors associated with patients developing unrealistic expectations; (2) the implications of having unrealistic hopes and the effects of raising patients' awareness about prognosis; and (3) patients' and caregivers' perspective on disclosure and their preferences for communication styles. Relevant studies were identified by searching electronic databases including Pubmed, EMBASE and ScienceDirect using multiple combinations of keywords, which yielded a total of 65 articles meeting the inclusion criteria. The discrepancy between patients' and doctors' expectations was associated with many factors including doctors' reluctance to disclose terminal prognoses and patients' ability to understand or accept such information. The majority of patients and caregivers expressed a desire for detailed prognostic information; however, varied responses have been reported on the preferred style of conveying such information. Communication styles have profound effects on patients' experience and treatment choices. Patients' views on disclosure are influenced by many cultural, psychological and illness-related factors, therefore individuals' needs must be considered when conveying prognostic information. More research is needed to identify communication barriers and the interventions that could be used to increase patients' satisfaction with palliative care.

  3. [Venous thromboembolism in patients with cancer].

    Science.gov (United States)

    Lecumberri, Ramón; Feliu, Jesús; Rocha, Eduardo

    2006-06-03

    The association between neoplastic diseases and venous thromboembolism (VTE) is known since long time ago. The nature of this association is bidirectional. On one hand, cancer increases the incidence of venous thrombosis and, on the other hand, the hemostatic system does play a key role in the tumorigenesis process. However, despite recent advances in the field, prophylaxis and treatment of VTE in cancer patients is still a challenge, due to the complexity of this type of patients. This review is focused on some important points regarding management of VTE in cancer patients such as physiopathology, epidemiology, search for hidden malignancy, prognostic impact, prophylaxis in the medical and surgical setting, or initial and long-term treatment.

  4. Survival of ovarian cancer patients in Denmark

    DEFF Research Database (Denmark)

    Edwards, Hellen McKinnon; Noer, Mette Calundann; Sperling, Cecilie Dyg;

    2016-01-01

    BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study...... period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were...... identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22...

  5. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population.

    Science.gov (United States)

    An, Yi; Kiang, Alan; Lopez, Jay Patrick; Kuo, Selena Z; Yu, Michael Andrew; Abhold, Eric L; Chen, Jocelyn S; Wang-Rodriguez, Jessica; Ongkeko, Weg M

    2012-01-01

    It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC) on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP), which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

  6. Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population.

    Directory of Open Access Journals (Sweden)

    Yi An

    Full Text Available It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP, which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

  7. EXPRESSING DISTRESS IN PATIENTS WITH ADVANCED CANCER

    Directory of Open Access Journals (Sweden)

    Maura Gabriela FELEA

    2014-11-01

    Full Text Available Negative emotions (distress are recognized as part of the psychological profile of patients diagnosed with advanced stage cancer. However, most patients are not accustomed to verbalize feelings towards their physician, and generally towards family and medical care personnel. The purpose of this paper is to analyze the expression of emotions by patients in advanced stages of cancer, respectively the means by which they get to express emotions. To this respect, we identified the most common types of emotions expressed, or metaphors used by patients to describe their emotions and topics that trigger emotions. Words and phrases most commonly used are in relation to: fear, anxiety, depression, guilt, negligence, concern. They are uttered in order to depict the network created between disclosed emotions and topics on health status, symptoms, adverse effects and therapeutic choice, patient privacy, and social and family issues.

  8. COPING STRATEGIES IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    J. R. Gardanova

    2015-01-01

    Full Text Available Diagnostics of psycho-emotional disorders of patients with malignant diseases of the prostate is not doubt, because timely correction contributes to the shortening of rehabilitation period and restoration of the quality of life of patients after treatment. Detection and diagnosis of prostate cancer for many patients is stressful and causes changes in the affective sphere, and manifests itself in increased levels of anxiety and depression in men. To cope with stress is possible due to the used coping strategies.Purpose. Studying the coping mechanisms in prostate cancer patients.Materials and methods. 56 men treated in FGBU "LRTS" Russian Ministry of Health. The average age was 65.7 ± 6.1 years. The average duration of the disease prostate cancer is 3 ± 2 months. All men were subjected to the standard algorithm for the evaluation of hormonal status, the PSA, taking a history, inspection and physical examination, magnetic resonance imaging and scintigraphy of bones of a skeleton. All the patients underwent laparoscopic radical prostatectomy. Psychological testing with the use of the method of "Coping test" the scale of reactive and personal anxiety for the differentiated evaluation of anxiety. Results. The most common for prostate cancer revealed constructive coping strategies are "planning solve", "selfcontrol" and "search of social support". According to the scale Spielberg–Hanin a high level of situational anxiety was revealed.Conclusion. According to the results of the research, patients with prostate cancer are likely to use constructive coping strategies, that leads to stabilization of psycho-emotional state of men and promotes more effective adaptation in the terms of stress, that is caused by treatment of prostate cancer.

  9. 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

  10. In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: A practical guide with case studies

    Directory of Open Access Journals (Sweden)

    Martina eMcDermott

    2014-03-01

    Full Text Available The development of a drug-resistant cell line can take from 3-18 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 optimising 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 2-8 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, H460 and temozolomide-resistant melanoma (Malme-3M and HT144 cell lines. Continuous selection produced 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 drug

  11. Predictors of treatment resistance in patients with schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Støvring, Henrik; Sørensen, Holger J

    2016-01-01

    BACKGROUND: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known...... about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. METHODS: In this population-based cohort study, we...

  12. Cancer Stem Cells: Targeting the Roots of Cancer, Seeds of Metastasis, and Sources of Therapy Resistance

    Science.gov (United States)

    Adorno-Cruz, Valery; Kibria, Golam; Liu, Xia; Doherty, Mary; Junk, Damian J.; Guan, Dongyin; Hubert, Chris; Venere, Monica; Mulkearns-Hubert, Erin; Sinyuk, Maksim; Alvarado, Alvaro; Caplan, Arnold I.; Rich, Jeremy; Gerson, Stanton L.; Lathia, Justin; Liu, Huiping

    2015-01-01

    With the goal to remove the roots of cancer, eliminate metastatic seeds, and overcome therapy resistance, the 2014 inaugural International Cancer Stem Cell (CSC) Conference at Cleveland, OH, convened together over 320 investigators, including 55 invited world-class speakers, 25 short oral presenters, and 100 poster presenters, to gain an in-depth understanding of CSCs and explore therapeutic opportunities targeting CSCs. The meeting enabled intriguing discussions on several topics including: genetics and epigenetics; cancer origin and evolution; microenvironment and exosomes; metabolism and inflammation; metastasis and therapy resistance; single cell and heterogeneity; plasticity and reprogramming; as well as other new concepts. Reports of clinical trials targeting CSCs emphasized the urgent need for strategically designing combinational CSC-targeting therapies against cancer. PMID:25604264

  13. VMAT planning study in rectal cancer patients

    OpenAIRE

    Shang, Jun; Kong, Wei; Wang, Yan-Yang; Ding, Zhe; Yan, Gang; Zhe, Hong

    2014-01-01

    Background To compare the dosimetric differences among fixed field intensity-modulated radiation therapy (IMRT), single-arc volumetric-modulated arc therapy (SA-VMAT) and double-arc volumetric-modulated arc therapy (DA-VMAT) plans in rectal cancer. Method Fifteen patients with rectal cancer previously treated with IMRT in our institution were selected for this study. For each patient, three plans were generated with the planning CT scan: one using a fixed beam IMRT, and two plans using the VM...

  14. RESISTANT HYPERTENSION IN A PATIENT WITH METABOLIC SYNDROME

    OpenAIRE

    O. M. Drapkina; J. S. Sibgatullina

    2016-01-01

    Clinical case of resistant hypertension in a patient with metabolic syndrome is presented. Features of hypertension in metabolic syndrome and features of metabolic syndrome in women of pre- and postmenopausal age are also considered. Understanding the features of metabolic syndrome in women, as well as features of hypertension and metabolic syndrome will improve the results of treatment in patients with resistant hypertension.

  15. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    Science.gov (United States)

    2015-09-01

    nitrogen) aliquot of PC3 cells (ATCC: human prostate adenocarcinoma). 2. Disperse into 75 cm2 flask containing RPMI 1640 media supplemented with 10% fetal ...compound #88 shows high cell killing efficacy in prostate cancer cell lines, including taxol resistant cells that stems from the induction of apoptosis...approach engages computational modeling to identify compounds that target a specific, mismatch repair protein-­‐dependent cell death pathway. A

  16. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    OpenAIRE

    Ömer Acar; Tarık Esen; Lack, Nathan A.

    2013-01-01

    Hindawi Publishing Corporation The ScientificWorld Journal Volume 2013, Article ID 379641, 8 pages http://dx.doi.org/10.1155/2013/379641 Review Article New Therapeutics to Treat Castrate-Resistant Prostate Cancer Ömer Acar,1 TarJk Esen,1,2 and Nathan A. Lack1 1 VKF American Hospital, Guzelbahce sokak, Nisantasi, Istanbul 34365, Turkey 2 School of Medicine, Koc¸ University, Rumelifeneri Yolu, Sariyer, Istanbul 34450, Turkey Correspondence should be addressed to Natha...

  17. Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

    Science.gov (United States)

    Caffo, Orazio; Lunardi, Andrea; Trentin, Chiara; Maines, Francesca; Veccia, Antonello; Galligioni, Enzo

    2016-01-01

    The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer.

  18. Integrative Molecular Profiling Reveals Asparagine Synthetase Is a Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Cogdell, David; Dhillon, Jasreman; Tzelepi, Vassiliki; Efstathiou, Eleni; Koumakpayi, Ismaël H.; Saad, Fred; Luo, Dijun; Bismar, Tarek A.; Aparicio, Ana; Troncoso, Patricia; Navone, Nora; Zhang, Wei

    2013-01-01

    The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells. PMID:22245216

  19. Renal cancer in kidney transplanted patients.

    Science.gov (United States)

    Frascà, Giovanni M; Sandrini, Silvio; Cosmai, Laura; Porta, Camillo; Asch, William; Santoni, Matteo; Salviani, Chiara; D'Errico, Antonia; Malvi, Deborah; Balestra, Emilio; Gallieni, Maurizio

    2015-12-01

    Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90% of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.

  20. Cachexia in patients with oesophageal cancer.

    Science.gov (United States)

    Anandavadivelan, Poorna; Lagergren, Pernilla

    2016-03-01

    Oesophageal cancer is a debilitating disease with a poor prognosis, and weight loss owing to malnutrition prevails in the majority of patients. Cachexia, a multifactorial syndrome characterized by the loss of fat and skeletal muscle mass and systemic inflammation arising from complex host-tumour interactions is a major contributor to malnutrition, which is a determinant of tolerance to treatment and survival. In patients with oesophageal cancer, cachexia is further compounded by eating difficulties owing to the stage and location of the tumour, and the effects of neoadjuvant therapy. Treatment with curative intent involves exceptionally extensive and invasive surgery, and the subsequent anatomical changes often lead to eating difficulties and severe postoperative malnutrition. Thus, screening for cachexia by means of percentage weight loss and BMI during the cancer trajectory and survivorship periods is imperative. Additionally, markers of inflammation (such as C-reactive protein), dysphagia and appetite loss should be assessed at diagnosis. Routine assessments of body composition are also necessary in patients with oesophageal cancer to enable assessment of skeletal muscle loss, which might be masked by sarcopenic obesity in these patients. A need exists for clinical trials examining the effectiveness of therapeutic and physical-activity-based interventions in mitigating muscle loss and counteracting cachexia in these patients.

  1. Fluorescense laparoscopy in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    V. A. Lukin

    2013-01-01

    Full Text Available The results of fluorescence laparoscopy in 60 patients with gastric cancer in P.A.Herzen MCRI are represented in the article. All patients had gastric cancer stage III. Undifferentiated cancer was diagnosed in 3 (5% patients, signet ring cell carcinoma – in 42 (70%, low differentiated adenocarcinoma – in 15 (25%. Fluorescence diagnosis was performed using fluorescence laparoscope by Carl Storz (Germany with wavelengths 380-460 nm and alasens given per os at a dose of 30 mg/kg body weight 3 h before study. During the investigation the examination of parietal and visceral peritoneum, great omentum with instrumental revision of pelvic organs was made. The technique of fluorescence diagnosis and assessment of its results are described. According to results of the study occult tumor microdissemination over peritoneum was detected in 10 (16.7% patients. The sensitivity of fluorescence laparoscopy in patients with gastric cancer accounted for 87.5%, specificity – 76%. The data of fluorescence diagnosis allowed to perform staging of tumor process and influenced on following management. 

  2. Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer.

    Science.gov (United States)

    Nebeling, L C; Lerner, E

    1995-06-01

    Traditionally, a ketogenic diet is given to drug-resistant children with epilepsy to improve seizure control. Inducing a ketogenic state in patients with cancer may be a useful adjunct to cancer treatment by affecting tumor glucose metabolism and growth while maintaining the patient's nutritional status. A ketogenic diet consisting of 60% medium-chain triglyceride (MCT) oil, 20% protein, 10% carbohydrate, and 10% other dietary fats was provided to a select group of pediatric patients with advanced-stage cancer to test the effects of dietary-induced ketosis on tumor glucose metabolism. Issues of tolerance and compliance for patients consuming an oral diet (consisting of normal table foods and daily MCT oil "shakes") and for patients receiving an enteral formula are reviewed. Preliminary use of the MCT oil-based diet suggests a potential in pediatric patients with cancer.

  3. Tamoxifen-resistant breast cancer cells possess cancer stem-like cell properties

    Institute of Scientific and Technical Information of China (English)

    LIU Hui; ZHANG Heng-wei; SUN Xian-fu; GUO Xu-hui; HE Ya-ning; CUI Shu-de; FAN Qing-xia

    2013-01-01

    Background Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis.Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy.Although acquired resistance to endocrine treatment has been extensively studied,the underlying mechanisms are unclear.We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy.Therefore,we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.Methods Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively.Stem-cell markers (SOX-2,OCT-4,and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR.Morphological observation was performed to characterize EMT.Results After induction of TAM resistance,TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P <0.05),indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells.TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P <0.01),demonstrating the elevated CSC properties of TAM-R MCF7 cells.Consistently,qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2,OCT-4,and CD133,compared to those of WT MCF7 cells (P <0.05).Morphologically,TAM-R MCF7 cells showed a fibroblastic phenotype,but WT MCF7 cells were epithelial-like.After induction of TAM resistance,qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail,vimentin,and N-cadherin and decreased levels of E-cadherin,which are considered as EMT characteristics (P <0

  4. Kundalini yoga as a support therapy for cancer patients

    OpenAIRE

    Kröneck, Mia

    2016-01-01

    This study was designed to describe cancer patient’s experience of kundalini yoga and its effect on their internal coping resources. The intention of this study is to put forward kundalini yoga as a support therapy for cancer patients for improving their wellbeing during active cancer treatment. This is a descriptive study. An academic literature review was conducted for cancer, cancer treatment, internal coping resources and yoga as therapy topics. Four voluntary female cancer patients (...

  5. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Directory of Open Access Journals (Sweden)

    John Koren

    Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  6. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Science.gov (United States)

    Koren, John; Miyata, Yoshinari; Kiray, Janine; O'Leary, John C; Nguyen, Lana; Guo, Jianping; Blair, Laura J; Li, Xiaokai; Li, Xiokai; Jinwal, Umesh K; Cheng, Jin Q; Gestwicki, Jason E; Dickey, Chad A

    2012-01-01

    MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  7. Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

    Science.gov (United States)

    Robinson, Dan R; Wu, Yi-Mi; Vats, Pankaj; Su, Fengyun; Lonigro, Robert J; Cao, Xuhong; Kalyana-Sundaram, Shanker; Wang, Rui; Ning, Yu; Hodges, Lynda; Gursky, Amy; Siddiqui, Javed; Tomlins, Scott A; Roychowdhury, Sameek; Pienta, Kenneth J; Kim, Scott Y; Roberts, J Scott; Rae, James M; Van Poznak, Catherine H; Hayes, Daniel F; Chugh, Rashmi; Kunju, Lakshmi P; Talpaz, Moshe; Schott, Anne F; Chinnaiyan, Arul M

    2013-12-01

    Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies. A survey of The Cancer Genome Atlas (TCGA) identified four endometrial cancers with similar mutations of ESR1. The five new LBD-localized ESR1 mutations identified here (encoding p.Leu536Gln, p.Tyr537Ser, p.Tyr537Cys, p.Tyr537Asn and p.Asp538Gly) were shown to result in constitutive activity and continued responsiveness to anti-estrogen therapies in vitro. Taken together, these studies suggest that activating mutations in ESR1 are a key mechanism in acquired endocrine resistance in breast cancer therapy.

  8. Patient representatives' views on patient information in clinical cancer trials

    DEFF Research Database (Denmark)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. METHODS: Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I......-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. RESULTS: Two major themes emerged: emotional responses and cognitive...

  9. Protein Analytical Assays for Diagnosing, Monitoring, and Choosing Treatment for Cancer Patients

    Directory of Open Access Journals (Sweden)

    Alicia D. Powers

    2012-01-01

    Full Text Available Cancer treatment is often hindered by inadequate methods for diagnosing the disease or insufficient predictive capacity regarding therapeutic efficacy. Targeted cancer treatments, including Bcr-Abl and EGFR kinase inhibitors, have increased survival for some cancer patients but are ineffective in other patients. In addition, many patients who initially respond to targeted inhibitor therapy develop resistance during the course of treatment. Molecular analysis of cancer cells has emerged as a means to tailor treatment to particular patients. While DNA analysis can provide important diagnostic information, protein analysis is particularly valuable because proteins are more direct mediators of normal and diseased cellular processes. In this review article, we discuss current and emerging protein assays for improving cancer treatment, including trends toward assay miniaturization and measurement of protein activity.

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

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

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

  11. Fertility preservation in young patients with cancer

    Directory of Open Access Journals (Sweden)

    Virender Suhag

    2015-01-01

    Full Text Available Infertility can arise as a consequence of treatment of oncological conditions. The parallel and continued improvement in both the management of oncology and fertility cases in recent times has brought to the forefront the potential for fertility preservation in patients being treated for cancer. Many survivors will maintain their reproductive potential after the successful completion of treatment for cancer. However total body irradiation, radiation to the gonads, and certain high dose chemotherapy regimens can place women at risk for acute ovarian failure or premature menopause and men at risk for temporary or permanent azoospermia. Providing information about risk of infertility and possible interventions to maintain reproductive potential are critical for the adolescent and young adult population at the time of diagnosis. There are established means of preserving fertility before cancer treatment; specifically, sperm cryopreservation for men and in vitro fertilization and embryo cryopreservation for women. Several innovative techniques are being actively investigated, including oocyte and ovarian follicle cryopreservation, ovarian tissue transplantation, and in vitro follicle maturation, which may expand the number of fertility preservation choices for young cancer patients. Fertility preservation may also require some modification of cancer therapy; thus, patients' wishes regarding future fertility and available fertility preservation alternatives should be discussed before initiation of therapy.

  12. 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...

  13. Lung cancer in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    R Palacios

    2012-11-01

    Full Text Available Purpose: Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods: The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992–2012 were reviewed, and all patients with a lung cancer were analysed. Results: There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%, and smokers (96.6%; mean pack-years 35.2, with a median age of 48.0 (41.7–52.9 years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7% patients were Aids cases, and 29 (47.5% had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42–232, the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85–397, and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0% and 23 (38.3% cases, respectively. There were 49 (80.3% cases with advanced stages (III and IV at diagnosis. The distribution of treatments was: only palliative 23 (39.7%, chemotherapy 14 (24.1%, surgery and chemotherapy 8 (13.8%, radiotherapy 7 (12.1%, surgery 4 (6.9%, and other combined treatments 2 (3.4%. Forty-six (76.7% patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%. Conclusions: The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis

  14. Methicillin-resistant Staphylococcus sp. colonizing health care workers of a cancer hospital

    Directory of Open Access Journals (Sweden)

    Dayane de Melo Costa

    2014-09-01

    Full Text Available The aim of the study was to analyze epidemiological and microbiological aspects of oral colonization by methicillin-resistant Staphylococcus of health care workers in a cancer hospital. Interview and saliva sampling were performed with 149 health care workers. Antimicrobial resistance was determined by disk diffusion and minimum inhibitory concentration. Polymerase Chain Reaction, Internal Transcribed Spacer-Polymerase Chain Reaction and Pulsed Field Gel Electrophoresis were performed for genotypic characterization of methicillin-resistant Staphylococcus. Risk factors were determined by logistic regression. Methicillin-resistant Staphylococcus colonization prevalence was 19.5%, denture wearing (p = 0.03, habit of nail biting (p = 0.04 and preparation and administration of antimicrobial (p = 0.04 were risk factors identified. All methicillin-resistant Staphylococcus were S. epidermidis, 94.4% of them had mecA gene. Closely related and indistinguishable methicillin-resistant S. epidermidis were detected. These results highlight that HCWs which have contact with patient at high risk for developing infections were identified as colonized by MRSE in the oral cavity, reinforcing this cavity as a reservoir of these bacteria and the risk to themselves and patients safety, because these microorganisms may be spread by coughing and talking.

  15. Src and CXCR4 are involved in the invasiveness of breast cancer cells with acquired resistance to lapatinib.

    Science.gov (United States)

    De Luca, Antonella; D'Alessio, Amelia; Gallo, Marianna; Maiello, Monica R; Bode, Ann M; Normanno, Nicola

    2014-01-01

    Lapatinib is a dual EGFR and ErbB-2 tyrosine kinase inhibitor that has significantly improved the clinical outcome of ErbB-2-overexpressing breast cancer patients. However, patients inexorably develop mechanisms of resistance that limit the efficacy of the drug. In order to identify potential targets for therapeutic intervention in lapatinib-resistant patients, we isolated, from ErbB-2-overexpressing SK-Br-3 breast cancer cells, the SK-Br-3 Lap-R-resistant subclone, which is able to routinely grow in 1 µM lapatinib. Resistant cells have a more aggressive phenotype compared with parental cells, as they show a higher ability to invade through a matrigel-coated membrane. Lapatinib-resistant cells have an increased Src kinase activity and persistent levels of activation of ERK1/2 and AKT compared with parental cells. Treatment with the Src inhibitor saracatinib in combination with lapatinib reduces AKT and ERK1/2 phosphorylation and restores the sensitivity of resistant cells to lapatinib. SK-Br-3 Lap-R cells also show levels of expression of CXCR4 that are higher compared with parental cells and are not affected by Src inhibition. Treatment with saracatinib or a specific CXCR4 antibody reduces the invasive ability of SK-Br-3 Lap-R cells, with the two drugs showing cooperative effects. Finally, blockade of Src signaling significantly increases TRAIL-induced cell death in SK-Br-3 Lap-R cells. Taken together, our results demonstrate that breast cancer cells with acquired resistance to lapatinib have a more aggressive phenotype compared with their parental counterpart, and that Src signaling and CXCR4 play an important role in this phenomenon, thus representing potential targets for therapeutic intervention in lapatinib-resistant breast cancer patients.

  16. Therapeutic resistance in cancer:microRNA regulation of EGFR signaling networks

    Institute of Scientific and Technical Information of China (English)

    German G. Gomez; Jill Wykosky; Ciro Zanca; Frank B. Furnari; Webster K. Cavenee

    2013-01-01

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor (EGFR) regulate cellular homeostatic processes. EGFR activates downstream signaling cascades that promote tumor cell survival, proliferation and migration. Dysregulation of EGFR signaling as a consequence of overexpression, amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes. Consequently, concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR. However, limited therapeutic beneifts to cancer patients have been derived from EGFR-targeted therapies. A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses. Here, we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs (miRs) as downstream effector molecules utilized by EGFR to promote tumor initiation, progression and that play a role in resistance to EGFR inhibitors. We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.

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

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Pallisgård, Niels;

    2013-01-01

    OBJECTIVE: The increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian...... cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. PATIENTS AND METHODS: Major eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type......-free and overall survival in the intention-to-treat population was 2.7 months (2.5-3.2 months, 95% confidence interval) and 8.1 months (5.6-11.7 months, 95% confidence interval), respectively. The most common treatment-related grade 3 toxicities included skin toxicity (42%), fatigue (19%), and vomiting (12...

  18. Working with children of cancer patients.

    Science.gov (United States)

    Slivka, H H; Magill, L

    1993-02-01

    Through the use of verbal and nonverbal techniques, a social worker and music therapist have combined their fields into an integral therapeutic modality to provide patients with cancer and their children opportunities to experience intimacy in a time of crisis. Skilled verbal interventions and the sensitive application of the expressive and less threatening medium of music create a relaxed environment where families and patients may explore deeply and express freely.

  19. Mechanisms for Breast Cancer Cell Resistance to Doxorubicin and Solutions to Resistance and Side Effects

    Science.gov (United States)

    2001-10-01

    formaldehyde virtual crosslink 1523 pp. 1001N VVUU-LYJLVU/4P5bC 11U1t II1dLLCI "© 2000 Elsevier Science Inc . All rights reserved. PHI S0006-2952(00)00521-S... Science Inc . KEY WORDS. adriamycin; GSH conjugation; GST inhibition; multidrug resistance; MCF-7; DOX The resistance of cancer cells acquired upon exposure...with K, at 250 in the 1-2 ýLM range, scarcely dependent on their stereochemistry at C(7). BIOCHEM PHARMACOL 60;12:1915-1923, 2000. © 2000 Elsevier

  20. Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer.

    Science.gov (United States)

    Turkington, R C; Longley, D B; Allen, W L; Stevenson, L; McLaughlin, K; Dunne, P D; Blayney, J K; Salto-Tellez, M; Van Schaeybroeck, S; Johnston, P G

    2014-02-06

    The discovery of underlying mechanisms of drug resistance, and the development of novel agents to target these pathways, is a priority for patients with advanced colorectal cancer (CRC). We previously undertook a systems biology approach to design a functional genomic screen and identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of drug resistance. The aim of this study was to examine the role of FGFR4 in drug resistance using RNAi and the small-molecule inhibitor BGJ398 (Novartis). We found that FGFR4 is highly expressed at the RNA and protein levels in colon cancer tumour tissue compared with normal colonic mucosa and other tumours. Silencing of FGFR4 reduced cell viability in a panel of colon cancer cell lines and increased caspase-dependent apoptosis. A synergistic interaction was also observed between FGFR4 silencing and 5-fluorouracil (5-FU) and oxaliplatin chemotherapy in colon cancer cell lines. Mechanistically, FGFR4 silencing decreased activity of the pro-survival STAT3 transcription factor and expression of the anti-apoptotic protein c-FLIP. Furthermore, silencing of STAT3 resulted in downregulation of c-FLIP protein expression, suggesting that FGFR4 may regulate c-FLIP expression via STAT3. A similar phenotype and downstream pathway changes were observed following FGFR4 silencing in cell lines resistant to 5-FU, oxaliplatin and SN38 and upon exposure of parental cells to the FGFR small-molecule inhibitor BGJ398. Our results indicate that FGFR4 is a targetable regulator of chemo-resistance in CRC, and hence inhibiting FGFR4 in combination with 5-FU and oxaliplatin is a potential therapeutic strategy for this disease.

  1. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer.

    Science.gov (United States)

    Matassa, D S; Amoroso, M R; Lu, H; Avolio, R; Arzeni, D; Procaccini, C; Faicchia, D; Maddalena, F; Simeon, V; Agliarulo, I; Zanini, E; Mazzoccoli, C; Recchi, C; Stronach, E; Marone, G; Gabra, H; Matarese, G; Landriscina, M; Esposito, F

    2016-09-01

    Tumour cells have long been considered defective in mitochondrial respiration and mostly dependent on glycolytic metabolism. However, this assumption is currently challenged by several lines of evidence in a growing number of tumours. Ovarian cancer (OC) is one of the most lethal cancers worldwide, but it continues to be a poorly understood disease and its metabolic features are far to be elucidated. In this context, we investigated the role of tumour necrosis factor receptor-associated protein 1 (TRAP1), which is found upregulated in several cancer types and is a key modulator of tumour cell metabolism. Surprisingly, we found that TRAP1 expression inversely correlated with grade, stage and lower survival in a large cohort of OC patients. Accordingly, TRAP1 silencing induced resistance to cisplatin, resistant cells showed increased oxidative metabolism compared with their sensitive counterpart, and the bioenergetics cellular index of higher grade tumours indicated increased mitochondrial respiration. Strikingly, cisplatin resistance was reversible upon pharmacological inhibition of mitochondrial oxidative phosphorylation by metformin/oligomycin. At molecular level, increased oxidative metabolism in low TRAP1-expressing OC cells and tissues enhanced production of inflammatory mediators such as interleukin (IL)-6 and IL-8. Mechanistically, we identified members of the multidrug resistance complex (MDR) as key mediators of such metabolism-driven, inflammation-induced process. Indeed, treatment of OC cell lines with TNFα and IL6 induced a selective increase in the expression of TAP1 and multidrug resistance protein 1, whereas TAP1 silencing sensitized cells to cisplatin-induced apoptosis. Our results unveil a novel role for TRAP1 and oxidative metabolism in cancer progression and suggest the targeting of mitochondrial bioenergetics to increase cisplatin efficacy in human OC.

  2. [Treatment of elderly patients with breast cancer

    DEFF Research Database (Denmark)

    Paaschburg, B.; Pedersen, A.; Tuxen, M.K.;

    2008-01-01

    The latest investigations have been searched in order to present new guidelines for the treatment of elderly patients with primary breast cancer. It is concluded that breast-conserving surgery should be offered as well as the sentinel node technique. Axillary lymph node dissection is not necessary...

  3. Pharmacogenetics of antiemetics in Indonesian cancer patients

    NARCIS (Netherlands)

    Perwitasari, Dyah Aryani

    2012-01-01

    Nausea and vomiting are well known side effects related to chemotherapy. Indeed, nausea and vomiting are the most distressing side effects of chemotherapy in cancer patients. Dopamine, serotonin and neurokinin1 are thought to be the neurotransmitters that play role in the pathophysiology of Chemothe

  4. Multidimensional fatigue and its correlates in hospitalised advanced cancer patients.

    NARCIS (Netherlands)

    Echteld, M.A.; Passchier, J.; Teunissen, S.; Claessen, S.; Wit, R. de; Rijt, C.C.D. van der

    2007-01-01

    Although fatigue is a multidimensional concept, multidimensional fatigue is rarely investigated in hospitalised cancer patients. We determined the levels and correlates of multidimensional fatigue in 100 advanced cancer patients admitted for symptom control. Fatigue dimensions were general fatigue (

  5. Communication in Cancer Care (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about communicating with the cancer patient and his or her family, including unique aspects of communication with cancer patients, factors affecting communication, and training in communication skills.

  6. Is Chemo Overused in Younger Colon Cancer Patients?

    Science.gov (United States)

    ... fullstory_163245.html Is Chemo Overused in Younger Colon Cancer Patients? Study found the treatment often wasn't ... 25, 2017 (HealthDay News) -- Young and middle-aged colon cancer patients may be getting chemotherapy more often than ...

  7. MiR-30a Decreases Multidrug Resistance (MDR) of Gastric Cancer Cells

    Science.gov (United States)

    Li, Chunying; Zou, Jinhai; Zheng, Guoqi; Chu, Jiankun

    2016-01-01

    Background The effectiveness of chemotherapy for gastric cancer is largely limited by either intrinsic or acquired drug resistance. In this study, we aimed to explore the association between miR-30a dysregulation and multidrug resistance (MDR) in gastric cancer cells. Material/Methods We recruited 20 patients with advanced gastric cancer. Chemosensitivity was assessed after completion of the chemotherapy. SGC-7901 and SGC-7901/DDP cells were transfected for miR-30a overexpression or knockdown. Then, MTT assay was performed to assess the IC50 of DPP and 5-FU in SGC-7901 and SGC-7901/DDP cells. Flow cytometry analysis was used to detect DPP- and 5-FU-induced cell apoptosis. Western blot analysis and immunofluorescence staining were used to assess EMT of the cells. Results MiR-30a was significantly downregulated in the chemoresistant tissues. In both SGC-7901 and SGC-7901/DDP cells, miR-30a overexpression decreased the expression of P-gp, a MDR-related protein. MTT assay and flow cytometry analysis showed that miR-30a inhibition increased chemoresistance, while miR-30a overexpression decreased chemoresistance in gastric cancer cells. Both Western blot analysis and immunofluorescence staining confirmed that miR-30a inhibition decreased E-cadherin but increased N-cadherin in SGC-7901 cells, while miR-30a overexpression increased E-cadherin but decreased N-cadherin in SGC-7901 cells. Conclusions MiR-30a can decrease multidrug resistance (MDR) of gastric cancer cells. It is also an important miRNA modulating EMT of the cancer cells.

  8. MEK activity controls IL-8 expression in tamoxifen-resistant MCF-7 breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Jeon, Myeongjin; Lee, Jeong Eon; Nam, Seok Jin

    2016-04-01

    Although tamoxifen reduces disease progression, tamoxifen resistance occurs during the course of estrogen receptor-positive [ER+] breast cancer treatment. In the present study, we investigated the possibility that interleukin-8 (IL-8) is a prognostic marker for tamoxifen resistance and aimed to clarify the regulation of IL-8 expression in tamoxifen-resistant cells. Clinically, IL-8 expression is positively correlated with survival in luminal A type breast cancer patients, but not in luminal B type breast cancer patients. In addition, the levels of IL-8 mRNA and protein expression were significantly increased in tamoxifen-resistant (TamR) cells compared to tamoxifen-sensitive (TamS) cells. To determine the regulatory mechanism of IL-8 expression in TamR cells, we analyzed the activities of signaling molecules. Our results showed that the phosphorylation levels of MEK and Akt were markedly increased in TamR cells, but there was no change in the phosphorylation level of p38 MAPK. On the contrary, we observed that elevated IL-8 mRNA expression was suppressed by a specific MEK1/2 inhibitor, UO126, but not by the specific PI-3K inhibitor LY294002, in TamR cells, whereas, we found that overexpression of constitutively active-MEK (CA-MEK) significantly increased the levels of IL-8 mRNA expression in TamS cells. Finally, we investigated the effect of the specific CXCR1/2 inhibitor SB225002 on anchorage-independent growth of TamR cells, and found that the growth was completely suppressed by SB225002. Taken together, our results demonstrate that IL-8 expression is regulated through a MEK/ERK-dependent pathway in TamR cells, suggesting that IL-8 and its receptors may be promising therapeutic targets for overcoming tamoxifen resistance.

  9. Sorafenib overcomes irinotecan resistance in colorectal cancer by inhibiting the ABCG2 drug-efflux pump.

    Science.gov (United States)

    Mazard, Thibault; Causse, Annick; Simony, Joelle; Leconet, Wilhem; Vezzio-Vie, Nadia; Torro, Adeline; Jarlier, Marta; Evrard, Alexandre; Del Rio, Maguy; Assenat, Eric; Martineau, Pierre; Ychou, Marc; Robert, Bruno; Gongora, Celine

    2013-10-01

    Despite recent advances in the treatment of colorectal cancer (CRC), tumor resistance is a frequent cause of chemotherapy failure. Therefore, new treatment options are needed to improve survival of patients with irinotecan-refractory CRCs, particularly those bearing KRAS mutations that preclude the use of anti-EGFR therapies. In this study, we investigated whether sorafenib could reverse irinotecan resistance, thereby enhancing the therapeutic efficacy of routinely used irinotecan-based chemotherapy. We used both in vitro (the HCT116, SW48, SW620, and HT29 colon adenocarcinoma cell lines and four SN-38-resistant HCT-116 and SW48 clones) and in vivo models (nude mice xenografted with SN-38-resistant HCT116 cells) to test the efficacy of sorafenib alone or in combination with irinotecan or its active metabolite, SN-38. We have shown that sorafenib improved the antitumoral activity of irinotecan in vitro, in both parental and SN-38-resistant colon adenocarcinoma cell lines independently of their KRAS status, as well as in vivo, in xenografted mice. By inhibiting the drug-efflux pump ABCG2, sorafenib favors irinotecan intracellular accumulation and enhances its toxicity. Moreover, we found that sorafenib improved the efficacy of irinotecan by inhibiting the irinotecan-mediated p38 and ERK activation. In conclusion, our results show that sorafenib can suppress resistance to irinotecan and suggest that sorafenib could be used to overcome resistance to irinotecan-based chemotherapies in CRC, particularly in KRAS-mutated tumors.

  10. Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

    Science.gov (United States)

    Pinto, Filipe; Pértega-Gomes, Nelma; Vizcaíno, José R.; Andrade, Raquel P.; Cárcano, Flavio M.; Reis, Rui Manuel

    2016-01-01

    Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients. PMID:27049720

  11. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  12. Sipuleucel-T: autologous cellular immunotherapy for men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.

    Science.gov (United States)

    Sims, Robert B

    2011-01-01

    Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  13. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    OpenAIRE

    Sims, Robert B.

    2011-01-01

    Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  14. Novel therapeutic approaches for the treatment of castration-resistant prostate cancer.

    Science.gov (United States)

    Heidegger, Isabel; Massoner, Petra; Eder, Iris E; Pircher, Andreas; Pichler, Renate; Aigner, Friedrich; Bektic, Jasmin; Horninger, Wolfgang; Klocker, Helmut

    2013-11-01

    Prostate cancer is a leading cause of cancer death in men in developed countries. Once the tumor has achieved a castration-refractory metastatic stage, treatment options are limited with the average survival of patients ranging from two to three years only. Recently, new drugs for treatment of castration-resistant prostate cancer (CRPC) have been approved, and others are in an advanced stage of clinical testing. In this review we provide an overview of the new therapeutic agents that arrived in the clinical praxis or are tested in clinical studies and their mode of action including hormone synthesis inhibitors, new androgen receptor blockers, bone targeting and antiangiogenic agents, endothelin receptor antagonists, growth factor inhibitors, novel radiotherapeutics and taxanes, and immunotherapeutic approaches. Results and limitations from clinical studies as well as future needs for improvement of CRPC treatments are critically discussed.

  15. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer

    NARCIS (Netherlands)

    M.F.E. Godinho (Marcia F.E.); A.M. Sieuwerts (Anieta); M.P. Look (Maxime); D.N. Meijer (Dies); J.A. Foekens (John); L.C.J. Dorssers (Lambert); T.L.A. van Agthoven (Thecla)

    2010-01-01

    textabstractBackground:Breast cancer anti-oestrogen resistance 4 (BCAR4) was identified in a search for genes involved in anti-oestrogen resistance in breast cancer. We explored whether BCAR4 is predictive for tamoxifen resistance and prognostic for tumour aggressiveness, and studied its function.Me

  16. Association of insulin resistance with breast, ovarian, endometrial and cervical cancers in non-diabetic women.

    Science.gov (United States)

    Sun, Wanwan; Lu, Jieli; Wu, Shengli; Bi, Yufang; Mu, Yiming; Zhao, Jiajun; Liu, Chao; Chen, Lulu; Shi, Lixin; Li, Qiang; Yang, Tao; Yan, Li; Wan, Qin; Liu, Yan; Wang, Guixia; Luo, Zuojie; Tang, Xulei; Chen, Gang; Huo, Yanan; Gao, Zhengnan; Su, Qing; Ye, Zhen; Wang, Youmin; Qin, Guijun; Deng, Huacong; Yu, Xuefeng; Shen, Feixia; Chen, Li; Zhao, Liebin; Wang, Tiange; Sun, Jichao; Xu, Min; Xu, Yu; Chen, Yuhong; Dai, Meng; Zhang, Jie; Zhang, Di; Lai, Shenghan; Li, Donghui; Ning, Guang; Wang, Weiqing

    2016-01-01

    Hyperinsulinemia and insulin resistance were reported to play a crucial role in diabetes-cancer relationship. This study aimed to explore the associations between insulin resistance and several female cancers in a non-diabetic population. This cross-sectional study was conducted in 121,230 middle-aged and elderly non-diabetic women. Cancer diagnosis was self-reported and further validated by medical records. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.50. The prevalence of both premenopausal and postmenopausal breast cancer, postmenopausal ovarian cancer and premenopausal endometrial cancer were higher in insulin-resistant participants than in insulin-sensitive participants (premenopausal breast cancer, 0.45 vs 0.28%; postmenopausal breast cancer, 0.86 vs 0.63%; postmenopausal ovarian cancer, 0.17 vs 0.09%; premenopausal endometrial cancer, 0.43 vs 0.25%, respectively, all P insulin resistance had higher odds ratio (OR) of breast cancer, both premenopausal and postmenopausal (OR 1.98, 95% confidence interval (CI) 1.19-3.32; OR 1.29, 95% CI 1.01-1.63), postmenopausal ovarian cancer (OR 2.17, 95% CI 1.10-3.40) as well as total endometrial cancer (OR 1.47, 95% CI 1.02-2.12). Subgroup analysis revealed that the possitive association between insulin resistance and risk of prevalent breast cancer was observed in popualtion with younger age, overweight or obesity, higher education and impaired glucose tolerance (IGR). No relationships were observed for the risk of prevalent cervical cancers with insulin resistance. Non-diabetic women with insulin resistance had higher risk of prevalent breast, ovarian and endomatrial cancer, which suggests special attentions to these female cancer screening and prevention.

  17. Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone

    DEFF Research Database (Denmark)

    Brasso, Klaus; Thomsen, Frederik B; Schrader, Andres J

    2015-01-01

    , AND PARTICIPANTS: Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment...... prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. RESULTS AND LIMITATIONS: We identified 137 patients who prior to enzalutamide had progressed following a median....... Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS. CONCLUSIONS: Median OS...

  18. Deregulation of let-7e in epithelial ovarian cancer promotes the development of resistance to cisplatin

    Science.gov (United States)

    Cai, J; Yang, C; Yang, Q; Ding, H; Jia, J; Guo, J; Wang, J; Wang, Z

    2013-01-01

    Drug resistance remains a major clinical obstacle to successful treatment in ovarian cancer patients, and the evidence of microRNAs involvement in drug resistance has been emerging recently. In this report, we investigated the role of let-7e in the development of cisplatin-resistant ovarian cancer. On the cellular level, let-7e expression was significantly reduced in cisplatin-resistant human epithelial ovarian cancer (EOC) cell line A2780/CP compared with parental A2780 cell and decreased in a concentration-dependent manner in A2780, SKOV3 and ES2 cells treated with cisplatin. Overexpression of let-7e by transfection of agomir could resensitize A2780/CP and reduce the expression of cisplatin-resistant-related proteins enhancer of zeste 2 (EZH2) and cyclin D1 (CCND1), whereas let-7e inhibitors increased resistance to cisplatin in parental A2780 cells. Quantitative methylation-specific PCR analysis showed hypermethylation of the CpG island adjacent to let-7e in A2780/CP cells, and demethylation treatment with 5-aza-CdR or transfection of pYr-let-7e-shRNA plasmid containing unmethylated let-7e DNA sequence could restore let-7e expression and partly reduce the chemoresistance. In addition, cisplatin combined with let-7e agomirs inhibited the growth of A2780/CP xenograft more effectively than cisplatin alone. Diminished expression of EZH2 and CCND1 and higher cisplatin concentrations in tumor tissue of mice subjected to administration of let-7e agomirs in addition to cisplatin were revealed by immunohistochemistry and atomic absorption spectroscopy, respectively. Taken together, our findings suggest that let-7e may act as a promising therapeutic target for improvement of the sensibility to cisplatin in EOC. PMID:24100610

  19. Research Progress of the Resistance Mechanism of Non-small Cell Lung Cancer 
to EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Huihui LIU

    2013-10-01

    Full Text Available Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months, most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

  20. Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts.

    Science.gov (United States)

    Lipner, Matthew B; Marayati, Raoud; Deng, Yangmei; Wang, Xianxi; Raftery, Laura; O'Neil, Bert H; Yeh, Jen Jen

    2016-01-01

    There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics.

  1. miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27(kip1) pathway.

    Science.gov (United States)

    Wang, Dan-Dan; Yang, Su-Jin; Chen, Xiu; Shen, Hong-Yu; Luo, Long-Ji; Zhang, Xiao-Hui; Zhong, Shan-Liang; Zhao, Jian-Hua; Tang, Jin-Hai

    2016-11-01

    The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27 (kip1) pathway. Firstly, in vivo, we verified that miR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their negative controls, respectively. The results showed that inhibition of miR-222 in MCF-7/Adr significantly increased the expressions of PTEN and p27 (kip1) and decreased phospho-Akt (p-Akt) both in mRNA and protein levels (p cancer cells to Adr through PTEN/Akt/p27 (kip1) signaling pathway, which provided a potential target to increase the sensitivity to Adr in breast cancer treatment and further improved the prognosis of breast cancer patients.

  2. [Selenium and oxidative stress in cancer patients].

    Science.gov (United States)

    Gorozhanskaia, É G; Sviridova, S P; Dobrovol'skaia, M M; Zybrikhina, G N; Kashnia, Sh R

    2013-01-01

    In order to identify the features of violations of free-radical processes in blood serum of 94 untreated cancer patients with different localization of the tumor (cancer of the stomach, colon, breast, ovarian, hemoblastoses) were determined selenium levels and indicators of oxidative stress (sum of metabolites of nitrogen--NOx, the level of superoxide dismutase--Cu/ZnSOD and malondiialdehyde-MDA, and the activity of catalase). In addition, 40 patients with malignant liver disease and clinical signs of liver failure in the early postoperative period was carried out a comparative evaluation of the efficacy of selenium-containing drug "Selenaze" (sodium selenite pentahydrate). It was found that selenium levels in cancer patients by 25-30% below the norm of 110-120 mg/l at a rate of 73.0 +/- 2.6 mg/l. Low levels of NOx was detected in patients with all tumor localizations (22.1 +/- 1.1 microM, with normal range 28.4 +/- 0.9 microM). The exceptions were patients with extensive malignant process in the liver, in which the NOx levels were significantly higher than normal (p selenium levels by 10-12%, which was accompanied by a decrease in the content of SOD and NOx, and contributed to earlier recovery of detoxic and synthetic liver function. These findings point to an intensification of oxidative stress and metabolic disorders in the malignant process, which is the basis for metabolic correction.

  3. Fungal agents isolated from cancer patients.

    Science.gov (United States)

    Alvarez Gasca, M A; Argüero Licea, B; Pliego Castañeda, A; García Tena, S

    1998-01-01

    With the aim to know the frequency of mycotic agents in patients with different types of cancer, samples were obtained from 81 patients from the Hospital de Oncología, Centro Médico Nacional Siglo XXI, IMSS from May 1995 through May 1996. In a conventional grouping seven (7) ambulatory patients were found in early stages, twenty seven (27) occasionally hospitalized patients were found in intermediate stage and forty seven (47) hospitalized patients in terminal stage of cancer. The different samples were processed through routine mycologycal methods and the following fungi species were isolated and identified: fifty four strains (58%) of Candida albicans followed by eleven strains (11.8%) of Candida tropicalis, six strains (6.45%) of Candida parapsilosis, five strains (5.37%) of Candida krusei, four strains (4.3%) of Candida humicola and five strains (5.37%) of Rodothorula rubra. From medical devices like catheter tips, drainage catheters (Pen rouse, Foley) and gallbladder catheters; four (4) strains of C. albicans, three (3) strains of Rodothorula rubra and two (2) strains of Aspergillus sp were isolated. Of the Candida non albicans it was relevant to find C. krusei more frequently than Rodothorula rubra, Aspergillus sp and Penicillum sp. The frequency of the presence of fungi increases commensurately to the advancement of the clincal stage of the cancer.

  4. "Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2006-07-01

    Full Text Available Abstract Background In a significant proportion of metastatic breast cancer (MBC patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance, it is generally believed that the chance of achieving clinical benefit (CB with further endocrine therapy is minimal. Methods Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. Results In oestrogen receptor (ER positive MBC patients with assessable disease, CB was achieved in 159 (71.3% (1st line patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line, 46.1% (on 3rd line and 20% (on 4th line with a median duration of response (DOR in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7% patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line and 22.2% (on 3rd line with a median DOR in those with CB of 22.7 months and 14 months respectively. Conclusion The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

  5. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4.

    Science.gov (United States)

    Wei, Xueju; Wang, Weibin; Wang, Lanlan; Zhang, Yuanyuan; Zhang, Xian; Chen, Mingtai; Wang, Fang; Yu, Jia; Ma, Yanni; Sun, Guotao

    2016-04-01

    Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21.

  6. False-Positive Results of 68ga-Dotatate and 11c-Cholıne Pet/CT in Patients with Hormone-Resistant Prostate Cancer at Biochemical Recurrence are Related to Inflamed Lesions

    Directory of Open Access Journals (Sweden)

    Omar Alonso

    2015-02-01

    Full Text Available Objective: For an oncological tracer is relevant to know the uptake in inflamed/infected lesions. Thus, in the framework of a prospective trial aiming to compare the clinical value of 68Ga-DOTATATE and 11C-Choline PET/CT in patients with hormoneresistant prostate cancer at biochemical recurrence, we evaluated the false-positive findings of both techniques. Methods: The study group comprised 64 prostate cancer patients with PSA relapse under androgen deprivation therapy, with a median trigger PSA level of 4.25 ng/mL (range: 0.22-291 ng/mL. Within 1-2 weeks, a PET/CT study was performed with 68Ga-DOTATATE and 11C-Choline with an approximately dose of 100 MBq and 400 MBq, respectively, using a 64-slice PET/CT with time-of-flight correction. Correlative imaging, histopathology and/or clinical follow-up were considered as reference standard. Results: Both techniques showed positive local, regional and distant findings in 31 patients. Results were concordant in 57 cases (89%, with discordant findings observed in patients with bone (n=2 and regional lymph nodes lesions (n=5. On a per patient basis, sensitivity, specificity, positive and negative predictive values with their 95% confidence intervals were the same for both techniques: 0.82 (0.65-0.93, 0.90 (0.73-0.98, 0.90 (0.73-0.98 and 0.81 (0.65-0.93, respectively. False-positive lesions (n=5 were found, for both tracers, in 3 patients and were located in the prostate bed (n=1 and regional lymph nodes (n=4, being 3 discordant. In all cases, pathology revealed non-specific inflammatory lesions. Conclusion: This study demonstrates avid 68Ga-DOTATATE and 11C-Choline accumulation in inflammatory tissue, which may limit the specificity of these techniques for the detection of occult metastatic disease.

  7. Leuconostoc Spp. Bacteremia in a Patient with Sigmoid Colon Cancer

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    Havva Avcikucuk

    2013-10-01

    Full Text Available Leuconostoc species are opportunistic pathogens that rarely encountered as an infection agent. It has been reported that, this pathogen could cause infections especially in immunsupressive patients, after invasive procedures and antibiotic treatment. In this report, we aim to present a case with intrinsically vancomycin resistant Leuconostoc spp. that was isolated in blood culture. Fifty six years old male patient with type II diabetes mellitus and chronic obstructive pulmonary disease had been operated for sigmoid colon cancer one a half years ago. He was taken radiotherapy and chemotherapy right after the operation. The patient was admitted to our hospital with a complaint of stenosis in colostomy opening. Empiricial treatment was started for high fever. Gram positive coccus was reported in the blood culture(Bactec 9050, Becton-Dickinson, USA. The isolate was identified as Leuconostoc spp. with API 20 Strep (BioMerieux, French kit. Antibiotic susceptibility test was performed by the disk diffusion method according to CLSI (Clinical and Laboratory Standards Institute recommendations. The isolate was found susceptible to linezolid and quinupristin-dalfopristine, while it was resistant to penicilin, ampicillin, erythromycin, tetracycline, vancomycin and teicoplanin by the disk diffusion method. Vancomycin resistance was confirmed by E-test (AB Biodisk, Solna, Sweden.

  8. Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.

    Science.gov (United States)

    Huber, Marie L; Haynes, Laura; Parker, Chris; Iversen, Peter

    2012-02-22

    Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately addressing this alternative explanation for the trial results.

  9. [Treatment sequence using newly developed agents for men with castration resistant prostate cancer].

    Science.gov (United States)

    Fujimoto, Naohiro

    2014-12-01

    Abiraterone acetate(AA), enzalutamide (EZL) and cabazitaxel (CBZ) are becoming available in Japan. Clinical trials demonstrated the benefit of these agents in men with castration resistant prostate cancer (CRPC). However, data on sequence therapy using these agents are very limited. Based on the mechanisms of agents and clinical data, AA and EZL may be indicated in early stage and CBZ may be indicated in late stage of CRPC. Prostate cancer is significantly heterogeneous between individuals and useful biomarkers for deciding the best treatment are unavailable yet. Therefore, it is hard to establish a standard sequence of the treatments. Until clinical trials demonstrate the best treatment sequence, individualized therapy is required for each patient based on patient and disease characteristics.

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

    Directory of Open Access Journals (Sweden)

    Yuan LI

    2012-02-01

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

  11. Prediction of paclitaxel resistance in breast cancer: is CYP1B1*3 a new factor of influence?

    Science.gov (United States)

    Gehrmann, Mathias; Schmidt, Markus; Brase, Jan C; Roos, Peter; Hengstler, Jan G

    2008-07-01

    This article focuses on the recent findings by Marsh and colleagues, and also discusses recent findings with regards to breast cancer. Taxanes are amongst the most active agents in the treatment of breast cancer. However, many tumors are intrinsically resistant. Therefore, it would be an enormous progress, if factors could be identified that reliably differentiate between taxane-sensitive and -resistant patients. Marsh and colleagues analyzed the CYP1B1*3 (Val432Leu) polymorphism in patients with high-risk stage III and IV breast cancer, who received dose-intense paclitaxel in combination with doxorubicin and cyclophosphamide. They report for the first time that patients with two leucine alleles in codon 432 of CYP1B1 experience a longer progression-free survival compared with patients with the Val/Leu or Val/Val genotypes. If confirmed in independent cohorts CYP1B1*3 may prove to be an important factor that helps to differentiate between paclitaxel-sensitive and resistant breast cancer patients. However, the mechanism behind the association between CYP1B1*3 and prognosis of paclitaxel-treated patients remains unclear. Several studies provide strong evidence that CYP1B1 does not influence tumor progression independently from paclitaxel chemotherapy, and that CYP1B1 itself does not alter paclitaxel resistance. In addition, CYP1B1 mRNA expression does not correlate with paclitaxel sensitivity of primary tumor cells. Although still speculative, a possible explanation is an association between CYP1B1*3 with still unknown factors that, on their part, influence paclitaxel sensitivity. In the future, studies with SNP chips and studies on the transcriptome, proteome and metabolome level should be performed in order to identify signatures differentiating between paclitaxel-sensitive and -resistant patients.

  12. The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer

    DEFF Research Database (Denmark)

    Lin, Xue; Stenvang, Jan; Rasmussen, Mads Heilskov

    2015-01-01

    toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. Results: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38......Background: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic...... or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of 'DNA methylation entropy...

  13. Alterations in ovarian cancer cell adhesion drive taxol resistance by increasing microtubule dynamics in a FAK-dependent manner.

    Science.gov (United States)

    McGrail, Daniel J; Khambhati, Niti N; Qi, Mark X; Patel, Krishan S; Ravikumar, Nithin; Brandenburg, Chandler P; Dawson, Michelle R

    2015-04-17

    Chemorefractory ovarian cancer patients show extremely poor prognosis. Microtubule-stabilizing Taxol (paclitaxel) is a first-line treatment against ovarian cancer. Despite the close interplay between microtubules and cell adhesion, it remains unknown if chemoresistance alters the way cells adhere to their extracellular environment, a process critical for cancer metastasis. To investigate this, we isolated Taxol-resistant populations of OVCAR3 and SKOV3 ovarian cancer cell lines. Though Taxol-resistant cells neither effluxed more drug nor gained resistance to other chemotherapeutics, they did display increased microtubule dynamics. These changes in microtubule dynamics coincided with faster attachment rates and decreased adhesion strength, which correlated with increased surface β1-integrin expression and decreased focal adhesion formation, respectively. Adhesion strength correlated best with Taxol-sensitivity, and was found to be independent of microtubule polymerization but dependent on focal adhesion kinase (FAK), which was up-regulated in Taxol-resistant cells. FAK inhibition also decreased microtubule dynamics to equal levels in both populations, indicating alterations in adhesive signaling are up-stream of microtubule dynamics. Taken together, this work demonstrates that Taxol-resistance dramatically alters how ovarian cancer cells adhere to their extracellular environment causing down-stream increases in microtubule dynamics, providing a therapeutic target that may improve prognosis by not only recovering drug sensitivity, but also decreasing metastasis.

  14. Evolving landscape and novel treatments in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Paul J Toren; Martin E Gleave

    2013-01-01

    Treatment options for castrate-resistant prostate cancer (CRPC) have advanced in recent years and significantly improved the outlook for patients with this aggressive and lethal disease.Further understanding of the biologyof CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor (AR) directed therapy.The treatment landscape is rapidly changing and further biologically rationale,biomarker-based ongoing clinical trials are needed.We review the recent results of major clinical trials in CRPC.New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis,microtubules,chaperones,AR and intracellular kinases,as well as immunotherapy,radiopharmaceuticals and bone-targeted agents.The recent improvement in prognosis for CRPC brings continued optimism for further improvements.Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

  15. Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci

    Directory of Open Access Journals (Sweden)

    Ahu Kara

    2015-02-01

    Full Text Available Background:Vancomycin-resistant enterococci colonization has been reported to increase the risk of developing infections, including bloodstream infections.Aim:In this study, we aimed to share our experience with the vancomycin-resistant enterococci bloodstream infections following gastrointestinal vancomycin-resistant enterococci colonization in pediatric population during a period of 18 months.Method:A retrospective cohort of children admitted to a 400-bed tertiary teaching hospital in Izmir, Turkey whose vancomycin-resistant enterococci colonization was newly detected during routine surveillances for gastrointestinal vancomycin-resistant enterococci colonization during the period of January 2009 and December 2012 were included in this study. All vancomycin-resistant enterococci isolates found within 18 months after initial detection were evaluated for evidence of infection.Findings: Two hundred and sixteen patients with vancomycin-resistant enterococci were included in the study. Vancomycin-resistant enterococci colonization was detected in 136 patients (62.3% while they were hospitalized at intensive care units; while the remaining majority (33.0% were hospitalized at hematology-oncology department. Vancomycinresistant enterococci bacteremia was present only in three (1.55% patients. All these patients were immunosuppressed due to human immunodeficiency virus (one patient and intensive chemotherapy (two patients.Conclusion:In conclusion, our study found that 1.55% of vancomycin-resistant enterococcicolonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycinresistant enterococci bloodstream infections.

  16. Colorectal cancer stem cells : regulation of the phenotype and implications for therapy resistance

    NARCIS (Netherlands)

    Emmink, B.L.

    2014-01-01

    In this thesis different aspects of cancer stem cells in colorectal cancer are discribed. We focus on the therapy resistance of cancer stem cells and the effect that reactive oxygen species and hypoxia have on the cancer stem cell phenotype. For this purpose a novel culture method to propagate cance

  17. Fertility Preservation for Cancer Patients: A Review

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    Tosin Ajala

    2010-01-01

    Full Text Available Infertility can arise as a consequence of treatment of oncological conditions. The parallel and continued improvement in both the management of oncology and fertility cases in recent times has brought to the fore-front the potential for fertility preservation in patients being treated for cancer. Oncologists must be aware of situations where their treatment will affect fertility in patients who are being treated for cancer and they must also be aware of the pathways available for procedures such as cryopreservation of gametes and/or embryos. Improved cancer care associated with increased cure rates and long term survival, coupled with advances in fertility treatment means that it is now imperative that fertility preservation is considered as part of the care offered to these patients. This can only be approached within a multidisciplinary setting. There are obvious challenges that still remain to be resolved, especially in the area of fertility preservation in prepubertal patients. These include ethical issues, such as valid consent and research in the area of tissue retrieval, cryopreservation, and transplantation.

  18. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian;

    2013-01-01

    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...

  19. Lysophosphatidate induces chemo-resistance by releasing breast cancer cells from taxol-induced mitotic arrest.

    Directory of Open Access Journals (Sweden)

    Nasser Samadi

    Full Text Available BACKGROUND: Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals. METHODOLOGY/PRINCIPAL FINDINGS: In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase. CONCLUSIONS/SIGNIFICANCE: This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this

  20. Multiorgan resection in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Radovanović Dragan L.

    2004-01-01

    Full Text Available Introduction Multiorgan resection for a malignancy is a very comlicated procedure, but there is always the question: does it work? In everyday clinical practice gastric cancer in phases III and IV is rather frequent. Unfortunately, our patients are under the age of 55 years. D2 lymphadenectomy is not as extensive as D2 %/ or D3, so one must ask himself if multiorgan resection is worth the risk. Material and methods We evaluated two groups of patients: group I consisted of 34 patients who underwent total or subtotal gastrectomy, systematic lymphadenectomy and resection of one or more organs; group II (control consisted of 167 patients who underwent total or subtotal gastrectomy and systematic lymphadenectomy. These two groups of patients were analzyed in regard to: Bormann's classification, histopathologic type, early mortality, early postoperative complications, lymph node dissection and long-term survival. Results According to Bormann's classification the most common type of carcinoma in both groups was ulcerovegetativ tumor (70.6% in I and 58% in II. In the first group of patients a great number of patients had poorly differentiated adenocarcinomas (47%, while in the second group the most common histologic type was well differentiated intestinal carcinoma (28%. Patients with multiorgan resections had higher rates of early postoperative mortality and morbiditiy (mortality - 14.7% and complications - 26.5% than patients in control group (mortality - 4.8% and complications - 11.4%. The most frequent causes of postopertive mortality and morbidity were anastomotic leakage and wound infections in both groups. Metastatic lymph node invelvement was higher in the first group (41%, than in the second (28%. Long-term survival was best in the control group (38.5 months. Patients with multiorgan resection had better survival (25.4 months than inoperable cases (only 5 months. Discussion Patients undergoing multiorgan resection usually have advanced gastric

  1. Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo.

    Science.gov (United States)

    Li, Xin; Xu, Jinmei; Tang, Xi; Liu, Yilun; Yu, Xiaoping; Wang, Zhi; Liu, Weihua

    2016-05-01

    Trastuzumab (Herceptin®) is a recombinant humanized monoclonal antibody that is targeted against the human epidermal growth factor receptor 2 (HER2) tyrosine kinase receptor. Trastuzumab has been successfully used to treat patients with HER2-positive breast cancer, which accounts for ~25% of invasive breast cancer. However, the majority of patients who initially respond to trastuzumab demonstrate disease progression within 1 year of treatment. Therefore, identifying alternative drugs that overcome trastuzumab resistance and target HER2 may increase the magnitude and duration of response. Through a high‑throughput screening approach, we previously identified numerous anthocyanins that exert activity in HER2‑positive human breast cancer cell lines. The present study aimed to evaluate the anti‑tumor properties of anthocyanins against parental HER2‑positive cells and derivative trastuzumab‑resistant cells in vitro and in vivo. Cell proliferation, western blotting, Annexin V staining, migration and invasion assays were used to determine the effects of anthocyanins in vitro. Cyanidin-3-glucoside and peonidin-3-glucoside were able to inhibit phosphorylation of HER2, induce apoptosis, suppress migration and invasion, and inhibit tumor cell growth. Coupled with the fact that anthocyanins have been used for decades as supplements for the treatment of various types of cancer in Asia, the present study may have established a framework for the development and testing of anthocyanins as a novel treatment paradigm used to overcome classical trastuzumab-resistance and to improve the outcome of this disease.

  2. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK.

    Science.gov (United States)

    Zou, Dongling; Wang, Dong; Li, Rong; Tang, Ying; Yuan, Li; Long, Xingtao; Zhou, Qi

    2015-09-01

    Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.

  3. 基于PDTX模型研究原发性肺癌顺铂耐药与ERCC1 IGFBP5表达水平的关系%Relationship between cisplatin resistance of primary lung cancer and expression levels of ERCC1 and IGFBP5 in patient-derived tumor xenograft models

    Institute of Scientific and Technical Information of China (English)

    展丙香; 程龙强; 罗朋; 章菊; 王保龙

    2015-01-01

    Objective:To establish a lung cancer model of patient-derived tumor xenografts (PDTX) and to explore the relation-ship between primary cisplatin resistance and ERCC1 and IGFBP5 expression levels. Methods:Lung cancer tissues from 84 patients who underwent surgery were collected and implanted into nude mice. Patient characteristics for the first generation xenografts that were and were not engrafted were compared. Passage 3 xenografts were treated with cisplatin. The expression levels of ERCC1 and IGFBP5 in cisplatin-resistant and cisplatin-sensitive groups were detected using immunohistochemistry assay. Results:The model success rates were 32.14%(27/84) in first-generation xenografts, 88.89%(24/27) in second-generation xenografts, and 95.83%(23/24) in third-gener-ation xenografts. The tumorigenicity of first-generation xenografts was correlated with size, differentiation, clinical stage, and histologi-cal type. PDTX tumors maintain the histological type of parental tumors through serial passage in nude mice. ERCC1 expression level was significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group, whereas the IGFBP5 expression level was lower in the cisplatin-resistant group than in the cisplatin-sensitive group. Conclusion:Lung cancer PDTX models were successfully es-tablished, and histological characteristics of the primary cancers were retained. Therefore, the models may serve a function in preclini-cal research of lung tumor biology and for exploring the drug resistance mechanism of tumors. The cisplatin resistance of primary lung cancer may be correlated with the expression level of ERCC1 and IGFBP5 in lung carcinoma.%目的:构建PDTX(patient-derived tumor xenografts)肺癌模型,探索ERCC1、IGFBP5的表达水平与原发性肺癌顺铂耐药的关系.方法:取新鲜切除的84例肺癌组织移植于裸鼠(BALB/c)的皮下,构建PDTX模型,分析一代成瘤率与临床病理参数关系.三代移植瘤接受顺铂化疗,采

  4. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer

    Science.gov (United States)

    Li, Jianneng; Alyamani, Mohammad; Zhang, Ao; Chang, Kai-Hsiung; Berk, Michael; Li, Zhenfei; Zhu, Ziqi; Petro, Marianne; Magi-Galluzzi, Cristina; Taplin, Mary-Ellen; Garcia, Jorge A; Courtney, Kevin; Klein, Eric A; Sharifi, Nima

    2017-01-01

    Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation. DOI: http://dx.doi.org/10.7554/eLife.20183.001 PMID:28191869

  5. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer.

    Science.gov (United States)

    Li, Jianneng; Alyamani, Mohammad; Zhang, Ao; Chang, Kai-Hsiung; Berk, Michael; Li, Zhenfei; Zhu, Ziqi; Petro, Marianne; Magi-Galluzzi, Cristina; Taplin, Mary-Ellen; Garcia, Jorge A; Courtney, Kevin; Klein, Eric A; Sharifi, Nima

    2017-02-13

    Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.

  6. A single-center experience with abiraterone as treatment for metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Thortzen, Anita; Thim, Stine; Røder, Martin Andreas;

    2016-01-01

    BACKGROUND: Continuous stimulation of the androgen receptor (AR) axis is a prerequisite for growth in castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) is a potent inhibitor of extracellular and intracellular androgen synthesis by inhibition of the CYP-17 enzyme system, which...... has been shown to be up-regulated in CRPC. AA was recently introduced in the management of patients with metastatic CRPC (mCRPC) both before and after taxane-based chemotherapy. The purpose of this study is to report the initial clinical experience obtained from mCRPC patients managed on AA......% of the patients. Time to biochemical and radiological progression was 3.5 and 4.9 months, respectively. Overall survival was 13.2 months (95% CI: 9.0-17.4). CONCLUSION: Our initial experience with AA in the routine management of patients with mCRPC demonstrates an efficacy-effectiveness gap compared with clinical...

  7. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy.

    Science.gov (United States)

    El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard

    2016-03-14

    Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  8. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohamed El-Tanani

    2016-03-01

    Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  9. Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K521 Polymorphism.

    Science.gov (United States)

    Braig, Friederike; Kriegs, Malte; Voigtlaender, Minna; Habel, Beate; Grob, Tobias; Biskup, Karina; Blanchard, Veronique; Sack, Markus; Thalhammer, Anja; Ben Batalla, Isabel; Braren, Ingke; Laban, Simon; Danielczyk, Antje; Goletz, Steffen; Jakubowicz, Elzbieta; Märkl, Bruno; Trepel, Martin; Knecht, Rainald; Riecken, Kristoffer; Fehse, Boris; Loges, Sonja; Bokemeyer, Carsten; Binder, Mascha

    2017-03-01

    Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K521 (K-allele), which is expressed in >40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation. In several EGFR-mediated cancer models, cetuximab failed to inhibit downstream signaling or to kill cells harboring a high K-allele frequency. Cetuximab affinity for EGFR-K521 was reduced slightly, but ligand-mediated EGFR activation was intact. We found a lack of glycan sialyation on EGFR-K521 that associated with reduced protein stability, suggesting a structural basis for reduced cetuximab efficacy. CetuGEX, an antibody with optimized Fc glycosylation targeting the same epitope as cetuximab, restored HNSCC sensitivity in a manner associated with antibody-dependent cellular cytotoxicity rather than EGFR pathway inhibition. Overall, our results highlight EGFR-K521 expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients. Further, they offer a preclinical rationale for the use of ADCC-optimized antibodies to treat tumors harboring this EGFR isoform. Cancer Res; 77(5); 1188-99. ©2016 AACR.

  10. Insulin resistance and exercise tolerance in heart failure patients

    DEFF Research Database (Denmark)

    Snoer, Martin; Monk-Hansen, Tea; Olsen, Rasmus Huan

    2012-01-01

    Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.......Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage....

  11. MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1.

    Science.gov (United States)

    Wu, Di-di; Li, Xue-Song; Meng, Xiao-Na; Yan, Jing; Zong, Zhi-Hong

    2016-08-01

    Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P ovarian cancer in vivo (P ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

  12. Piecing the Puzzle Together: Docetaxel Cycles and Current Considerations in the Treatment of Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Feinman, Hannah E; Price, Douglas K; Figg, William D

    2017-02-25

    Docetaxel is the current first line therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is no standard number of docetaxel cycles given to patients. In their post hoc analysis of the Mainsail study, de Morrée et al. show that the number of docetaxel cycles administered to a patient is a significant factor contributing to overall survival. These findings warrant further investigation into the standardization of the number of docetaxel cycles administered.

  13. Partial response of liver metastases treated with abiraterone in castration-resistant prostate cancer: A case report

    OpenAIRE

    Marech,Ilaria; Vacca, Angelo; SIVESTRIS, NICOLA; Gnoni,Antonio; Lorusso, Vito

    2013-01-01

    Docetaxel is the current first-line treatment for castration-resistant prostate cancer (CRPC), following failure to respond to maximal androgen blockade (MAB). Patients who fail to respond to docetaxel may receive cabazitaxel or abiraterone; however, there are no recommendations on which of these two agents should be used first. Here, we present a case of a male patient suffering from CRPC with liver and lymph node metastases, in which abiraterone achieved a partial response, according to REC...

  14. Quantitative proteomics identifies central players in erlotinib resistance of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Lund, Rikke Raaen; Beck, Hans Christian

    compared to the parental cell line. By network analysis, we found cell survival, proliferation and migration to be induced, and apoptosis and adhesion to be repressed across the 3 resistant clones vs the parental cell line. The resistant cells generally lost phosphorylation of EGFR, MET, FGFR and Src......Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as 70% of patients show significant tumor regression when treated. However, all patients relapse due to development of acquired resistance, which in 43-50% of cases are caused......, but surprisingly not of AKT and FOXO1/3a, indicating that AKT is the main signaling hub for survival. Also Erk1/2 phsphorylation is pertained although at decreased levels. Conclusions: In conclusion, cancer-related networks such as proliferation and apoptosis were found to be regulated, supporting the validity...

  15. Not telling the truth: circumstances leading to concealment of diagnosis and prognosis from cancer patients.

    Science.gov (United States)

    Shahidi, J

    2010-09-01

    While autonomy has gradually become a key concept in the doctor-patient relationship, truth-telling is far from being the norm in many countries in the world. Despite the general agreement on the benefits of open communication between physicians and cancer patients, there is still strong resistance against disclosure of cancer diagnosis and prognosis in many cultures. Although fear of causing psychological morbidity to patients and their reluctance to find out the truth are two main justifications of non-disclosure attitudes, there are other important contributing factors that need to be further explored and better understood including those related to the relatives, doctors and healthcare systems. Cultural disparities in attitudes towards truth-telling persist; however, these differences should not be used as excuses not to respect the rights and individual preferences of cancer patients by making assumptions based on their age, sex, type of cancer, language and/or cultural background.

  16. Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer

    Science.gov (United States)

    Sobani, Zain A; Sawant, Ashwin; Jafri, Mikram; Correa, Amit Keith; Sahin, Ibrahim Halil

    2016-01-01

    Epidermal growth factor receptor (EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer (CRC). Evidence from clinical trials indicates that cetuximab and panitumumab (anti-EGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS (KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade. PMID:27777877

  17. Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study.

    Science.gov (United States)

    Adamsen, L; Stage, M; Laursen, J; Rørth, M; Quist, M

    2012-12-01

    Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer patients with advanced stages of disease, during treatment. The patients experienced physical, functional and emotional benefits. This study confirmed that supervised training in peer-groups was beneficial, even in a cancer population with full-blown symptom burden and poor prognosis.

  18. Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells.

    Science.gov (United States)

    Lan, Wei-Guang; Xu, Dian-Hong; Xu, Chen; Ding, Chang-Ling; Ning, Fang-Ling; Zhou, Yan-Li; Ma, Long-Bo; Liu, Chang-Min; Han, Xia

    2016-07-01

    The development of multidrug resistance (MDR) is a crucial cause of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Long non-coding RNAs (lncRNAs) have been proven to be critical in carcinogenesis and metastasis of gastric cancer. However, little is known about the roles of ANRIL (antisense non-coding RNA in the INK4 locus) in gastric cancer MDR. The aim of our study is to identify the biological function of ANRIL in gastric cancer MDR. In our results, ANRIL was highly expressed in gastric cancer tissues of cisplatin-resistant and 5-fluorouracil (5-FU)-resistant patients, and the same upregulation trends were observed in cisplatin-resistant cells (BGC823/DDP) and 5-FU-resistant cells (BGC823/5-FU). In addition, BGC823/DDP and BGC823/5-FU cells transfected with ANRIL siRNA and treated with cisplatin or 5-FU, respectively, exhibited significant lower survival rate, decreased invasion capability, and high percentage of apoptotic tumor cells. The influence of ANRIL knockdown on MDR was assessed by measuring IC50 of BGC823/DDP and BGC823/5-FU cells to cisplatin and 5-FU, the result showed that silencing ANRIL decreased the IC50 values in gastric cancer cells. Moreover, qRT-PCR and western blotting revealed that ANRIL knockdown decreased the expression of MDR1 and MRP1, both of which are MDR related genes; regression analysis showed that the expression of ANRIL positively correlated with the expression of MDR1 and MRP1, resprectively In summary, knockdown of lncRNA ANRIL in gastric cancer cells inhibits the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

  19. Why Breast Cancer Patients Seek Traditional Healers

    Directory of Open Access Journals (Sweden)

    Mazanah Muhamad

    2012-01-01

    Full Text Available Traditional healing is a common practice in low and middle income countries such as Malaysia. Eighty percent of Malaysians consult traditional healers or “bomoh” at some time in their life for health-related issues. The purpose of our study was to explore why breast cancer patients visit traditional healers. This is a qualitative study utilizing in-depth interviews with 11 cancer survivors who sought both traditional and Western medicine. The findings revealed the following reasons for which patients seek traditional healers: (1 recommendation from family and friends, (2 sanction from family, (3 perceived benefit and compatibility, (4 healer credibility, and (5 reservation with Western medicine and system delay. These factors work together and are strongly influenced by the Malaysian cultural context. The issue with the Western health system is common in a developing country with limited health facilities.

  20. CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro.

    Science.gov (United States)

    Zhu, Zhuangyan; Mu, Yaqin; Qi, Caixia; Wang, Jian; Xi, Guoping; Guo, Juncheng; Mi, Ruoran; Zhao, Fuxi

    2015-02-01

    Ovarian cancer (OC) is the most frequent cause of mortality among gynecological malignancies, with a 5-year survival rate of approximately 30%. The standard regimen for OC therapy includes a platinum agent combined with a taxane, to which the patients frequently acquire resistance. Resistance arises from the oxidation of anticancer drugs by CYP1B1, a cytochrome P450 enzyme overexpressed in malignant OC. The aim of the present study was to determine the role of CYP1B1 expression in the drug resistance of OC to the taxane, paclitaxel (PTX). Immunohistochemical staining was used to assess CYP1B1 expression in a panel of ovarian samples (53 primary cancer samples, 14 samples of metastastic cancer, 30 benign tumor samples and 19 normal tissue samples). Semi-quantitative RT-PCR was also performed to determine CYP1B1 expression in several OC cell lines. Finally, we used proliferation and toxicity assays, as well as a mouse xenograft model using nude mice to determine whether α-naphthoflavone (ANF), a CYP1B1 specific inhibitor, reduces resistance to PTX. CYP1B1 was overexpressed in the samples from primary and metastatic loci of epithelial ovarian cancers. In some cell lines, PTX induced CYP1B1 expression, which resulted in drug resistance. Exposure to ANF reduced drug resistance and enhanced the sensitivity of OC cells to PTX in vitro and in vivo. The expression profile of CYP1B1 suggests that it has the potential to be a useful diagnostic marker and prognostic factor for malignant OC. The inhibition of CYP1B1 expression by specific agents may provide a novel therapeutic strategy for the treatment of patients resistant to PTX and may improve the prognosis of these patients.

  1. Family Caregivers for Cancer Patients in Thailand

    OpenAIRE

    2013-01-01

    This integrative review was conducted to describe findings from Thai studies concerning family caregivers for cancer patients. Twenty-three studies that were published from 1994 to 2009 were considered. There were 15 quantitative studies and 8 qualitative studies. The stress and coping model developed by Lazarus and Folkman was the most popular theory that was used to guide the studies. The variables that were explored...

  2. Hematological Support of a Cancer Patient

    OpenAIRE

    Shear, J.M.; Rock, G.

    1988-01-01

    Transfusion medicine has come to function as a pivotal support in the treatment of cancer patients in the late 1980s. The authors of this article discuss the indications for, and uses of, various blood components, including packed red blood cells, leukocyte-poor and/or washed blood cells, random donor and single donor platelets, granulocyte concentrates, fresh frozen plasma, and cryoprecipitate. They also discuss common and not-so-common risks, reactions, and diseases associated with the tran...

  3. Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years.

    Science.gov (United States)

    Panczyk, Mariusz

    2014-08-01

    During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation, as a result of large international research projects (Human Genome Project, the 1000 Genomes Project International HapMap Project, and Programs for Genomic Applications NHLBI-PGA). This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer. For clinical use in the treatment of patients with colorectal cancer (CRC), in addition to fluoropyrimidines, another two new cytostatic drugs were allowed: irinotecan and oxaliplatin. Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted. The last 20 years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance. One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells. Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine. Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics. Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential. This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy. The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review.

  4. Distribution and drug resistance of pathogens causing pulmonary infections in lung cancer patients%肺癌患者肺部感染病原菌分布与耐药性分析

    Institute of Scientific and Technical Information of China (English)

    骆松梅; 纪建松; 朱超; 蒋晓梅

    2015-01-01

    OBJECTIVE To investigate the distribution and drug susceptibility of pathogens causing pulmonary in‐fections in the lung cancer patients so as to provide guidance for the clinical use of antibiotics .METHODS The clini‐cal data of 304 lung cancer patients who were hospitalized from Jan 2010 to Oct 2012 were retrospectively ana‐lyzed ,then the pathogens that were cultured from the submitted specimens collected from the participants with pulmonary infections were identified by using the microorganism identification system of Biomerivex ,the drug sus‐ceptibility testing was performed with the use of K‐B method ,and the relevant information was input to conduct the statistical analysis .RESULTS The pulmonary infections occurred in 86 lung cancer patients ,with the infection rate of 28 .3% .A total of 32 strains of pathogens have been isolated ,of which 81 .3% were the gram‐negative bacteria ,15 .6% were the gram‐positive cocci ,3 .1% were the fungi ,and 6 .3% were others ;the Haemophilus parainfluenzae,Klebsiellapneumoniae,Pseudomonasaeruginosa,Escherichiacoli,andAcinetobacterbauman‐nii were the species of the gram‐negative bacteria ;the Staphylococcus epidermidis ,Enterococcus f aecium ,and Staphylococcus hominis were the species of gram‐positive cocci ;the Candida albicans was the species of fungi . CONCLUSION The gram‐negative bacteria are dominant among the pathogens causing the pulmonary infections in the lung cancer patients ,and the study of the pathogens can provide guidance for reasonable clinical use of antibi‐otics for the lung cancer patients complicated with pulmonary infections .%目的:了解医院肺癌患者发生肺部感染病原菌种类以及药敏性,为其临床抗菌药物使用提供合理依据。方法回顾性分析医院2010年1月-2012年10月304例肺癌住院患者临床资料,对发生肺部感染患者送检标本检出的病原菌使用Biomerivex公司的微生物鉴定仪进行鉴定,药敏试验采

  5. [The cancer patient in science and society].

    Science.gov (United States)

    Günther, H

    1991-11-01

    The 2nd Dresden hematonocological meeting, organized by the Department of hematology and oncology of the Medical Academy "Carl Gustav Carus" and by the Tumorzentrum Dresden, focused ethical and anthropological topics. Death and dying, care and health prevention in modern oncology as well as the broad field of supportive care were discussed. The goal of the meeting was to find long time concepts of a patient oriented medical care in cancer patients. This will only be possible in interdisciplinary structures including philosophers, theologians, clinicians and general practitioners. The rapid progress of medical development in Eastern Germany must not forget this goal.

  6. Classification of neuropathic pain in cancer patients

    DEFF Research Database (Denmark)

    Brunelli, Cinzia; Bennett, Michael I; Kaasa, Stein

    2014-01-01

    and on the relevance of patient-reported outcome (PRO) descriptors for the screening of NP in this population. An international group of 42 experts was invited to participate in a consensus process through a modified 2-round Internet-based Delphi survey. Relevant topics investigated were: peculiarities of NP...... in patients with cancer, IASP NeuPSIG diagnostic criteria adaptation and assessment, and standardized PRO assessment for NP screening. Median consensus scores (MED) and interquartile ranges (IQR) were calculated to measure expert consensus after both rounds. Twenty-nine experts answered, and good agreement...

  7. How to present online information to older cancer patients

    NARCIS (Netherlands)

    Bol, N.

    2015-01-01

    Providing information to cancer patients is crucial within cancer care. As the Internet is becoming an increasingly valuable source of cancer information, it is important to consider the rapidly aging population when designing online cancer materials. Yet, the lack of studies and inconsistent findin

  8. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Matthew A Ingersoll

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

  9. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Muniyan, Sakthivel; D’Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G.; Bu, Xiu R.; Batra, Surinder K.; Lin, Ming-Fong

    2015-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents. PMID:26121643

  10. Rationale for stereotactic body radiation therapy in treating patients with oligometastatic hormone-naïve prostate cancer

    Directory of Open Access Journals (Sweden)

    Onita eBhattasali

    2013-12-01

    Full Text Available Despite advances in treatment for metastatic prostate cancer, patients eventually progress to castrate-resistant disease and ultimately succumb to their cancer. Androgen deprivation therapy (ADT is the standard treatment for metastatic prostate cancer and has been shown to improve median time to progression and median survival time. Research suggests that castrate-resistant clones may be present early in the disease process prior to the initiation of ADT. These clones are not susceptible to ADT and may even flourish when androgen-responsive clones are depleted. Stereotactic body radiation therapy (SBRT is a safe and efficacious method of treating clinically localized prostate cancer and metastases. In patients with a limited number of metastatic sites, SBRT may have a role in eliminating castrate-resistant clones and possibly delaying progression to castrate-resistant disease.

  11. Gastric varicella: two cases in cancer patients

    Directory of Open Access Journals (Sweden)

    Violeta María Sastre-Lozano

    Full Text Available Gastric involvement with the varicella-zoster virus is an uncommon clinical condition where early suspicion and diagnosis are important to prevent the consequences deriving from its high morbidity and mortality, which in immunocompromised patients oscillate between 9% and 41% according to the various series. Two cases of gastric involvement with the varicella-zoster virus (VZV in two patients with blood cancer are reported below. Gastric lesions are usually preceded by typical papulovesicular skin lesions. When gastric involvement is the first symptom of the disease its diagnosis and management may be delayed, which may entail severe consequences for immunocompromised patients. It is therefore that we suggest its inclusion in the algorithm for immunocompromised patients with abdominal pain and ulcer-like endoscopic lesions.

  12. THYROID HORMONE PROFILE IN EARLY BREAST CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    Renija Valiya

    2016-06-01

    Full Text Available BACKGROUND Breast cancer is the most common malignant tumour in women worldwide. The relationship between breast cancer and thyroid disease is a controversy. Many of the studies showed hypothyroidism as the commonly found thyroid abnormality in breast cancer. [1] There is considerable evidence for an increased risk of thyroid and breast cancer in patients with iodine deficiency. This ability of iodine to reduce the risk of breast cancer is attributed to the ability of iodine and its compounds to induce apoptosis so that appropriate cell death occurs. Instead, in the absence of optimum level of iodine in the body the transformed cells continue to grow and divide resulting in cancer. AIMS 1. To find out the association of thyroid hormones and breast cancer in early breast cancer patients. 2. To find out the association of thyroid peroxidase antibodies in early breast cancer patients. Settings Cases: 82 breast cancer patients in early stage who attended the breast clinic. Controls: 82 age matched controls (Between 25-80 years. Design: Case control study. MATERIALS AND METHOD In this study, investigated for thyroid function test (T3, T4, TSH and thyroid peroxide antibody level in 82 early breast cancer patients. STATISTICAL ANALYSIS SPSS 16. RESULTS Statistically significant low T4 and high TSH in breast cancer patients, along with elevated thyroid peroxidase antibody. CONCLUSION Compared to hyperthyroidism, hypothyroidism was found to be clinically significant in breast cancer patients

  13. NFkB signaling is important for growth of antiestrogen resistant breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Emdal, Kristina Bennet; Guerra, Barbara;

    2012-01-01

    resistant cell growth and a potential target for re-sensitizing resistant cells to endocrine therapy. We used an MCF-7-derived cell model for antiestrogen resistant breast cancer to investigate dependence on NF¿B signaling for antiestrogen resistant cell growth. We found that targeting NF¿B preferentially...... inhibited resistant cell growth. Antiestrogen resistant cells expressed increased p50 and RelB, and displayed increased phosphorylation of p65 at Ser529 and Ser536. Moreover, transcriptional activity of NF¿B after stimulation with tumor necrosis factor a was enhanced in antiestrogen resistant cell lines...... resistant cells increased sensitivity to tamoxifen treatment. Our data provide evidence that NF¿B signaling is enhanced in antiestrogen resistant breast cancer cells and plays an important role for antiestrogen resistant cell growth and for sensitivity to tamoxifen treatment in resistant cells. Our results...

  14. ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients

    NARCIS (Netherlands)

    L. Angus (Lindsay); N. Beije (Nick); A. Jäger (A.); J.W.M. Martens (John W. M.); S. Sleijfer (Stefan)

    2017-01-01

    textabstractMutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning t

  15. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

    NARCIS (Netherlands)

    Smit, EF; Fokkema, E; Biesma, B; Groen, HJM; Snoek, W; Postmus, PE

    1998-01-01

    The purpose of the study was to delineate the efficacy and toxicity of paclitaxel (Taxol, Bristol Myers Squibb) in the treatment of drug resistant small-cell lung cancer (SCLC). Patients with SCLC relapsing within 3 months of cytotoxic therapy received paclitaxel 175 mg m(-2) intravenously over 3 h

  16. Characteristics of critically ill cancer patients in the Netherlands

    NARCIS (Netherlands)

    Bos, Monique Martina Elisabeth Maria

    2013-01-01

    The care for acute complications occurring in cancer patients has changed dramatically in recent decades, not only for direct post-operative care following major cancer surgery, but also for cancer patients in need of organ function replacement due to the manifestation of their malignancy or toxicit

  17. Coping with cancer : The perspective of patients' relatives

    NARCIS (Netherlands)

    Hagedoorn, Mariet; Kreicbergs, Ulrika; Appel, Charlotte

    2011-01-01

    Cancer affects not only patients but also their loved ones. Material and methods. This paper presents a selective, narrative review of psychosocial consequences of cancer and its treatment for relatives of patients, including parents and siblings of children with cancer, children of parents with can

  18. Combined Phosphoproteomics and Bioinformatics Strategy in Deciphering Drug Resistant Related Pathways in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2014-01-01

    Full Text Available Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC, conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.

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

    OpenAIRE

    Serpe L; Gallicchio M; Canaparo R; Dosio F

    2014-01-01

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

  20. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with

  1. Ratio of phosphorylated HSP27 to nonphosphorylated HSP27 biphasically acts as a determinant of cellular fate in gemcitabine-resistant pancreatic cancer cells.

    Science.gov (United States)

    Kang, Dongxu; Choi, Hye Jin; Kang, Sujin; Kim, So Young; Hwang, Yong-Sic; Je, Suyeon; Han, Zhezhu; Kim, Joo-Hang; Song, Jae J

    2015-04-01

    Gemcitabine has been used most commonly as an anticancer drug to treat advanced pancreatic cancer patients. However, intrinsic or acquired resistance of pancreatic cancer to gemcitabine was also developed, which leads to very low five-year survival rates. Here, we investigated whether cellular levels of HSP27 phosphorylation act as a determinant of cellular fate with gemcitabine. In addition we have demonstrated whether HSP27 downregulation effectively could overcome the acquisition of gemcitabine resistance by using transcriptomic analysis. We observed that gemcitabine induced p38/HSP27 phosphorylation and caused acquired resistance. After acquisition of gemcitabine resistance, cancer cells showed higher activity of NF-κB. NF-κB activity, as well as colony formation in gemcitabine-resistant pancreatic cancer cells, was significantly decreased by HSP27 downregulation and subsequent TRAIL treatment, showing that HSP27 was a common network mediator of gemcitabine/TRAIL-induced cell death. After transcriptomic analysis, gene fluctuation after HSP27 downregulation was very similar to that of pancreatic cancer cells susceptible to gemcitabine, and then in opposite position to that of acquired gemcitabine resistance, which makes it possible to downregulate HSP27 to overcome the acquired gemcitabine resistance to function as an overall survival network inhibitor. Most importantly, we demonstrated that the ratio of phosphorylated HSP27 to nonphosphorylated HSP27 rather than the cellular level of HSP27 itself acts biphasically as a determinant of cellular fate in gemcitabine-resistant pancreatic cancer cells.

  2. Biomarkers predicting resistance to epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer with wild-type KRAS

    Directory of Open Access Journals (Sweden)

    Liu J

    2016-01-01

    Full Text Available Jiang Liu,* Jing Hu,* Lei Cheng, Wei Ren, Mi Yang, Baorui Liu, Li Xie, Xiaoping Qian The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: EGFR pathway is an important therapeutic target in human tumors, including metastatic colorectal cancer (mCRC. The advent of EGFR-targeted monoclonal antibodies panitumumab and cetuximab has generated promise for the treatment of mCRC and has largely improved patients’ progression-free survival (PFS and overall survival (OS. However, treatment with anti-EGFR monoclonal antibodies is only effective in a subset of mCRC patients with wild-type KRAS. This indicates that there are other factors affecting the efficacy of anti-EGFR monoclonal antibodies. Existing studies have demonstrated that among colorectal cancer patients with wild-type KRAS, harboring mutations of BRAF, PIK3CA, NRAS, or PTEN-null may demonstrate resistance to anti-EGFR-targeted therapy, and biomarkers detection can provide better-personalized treatment for mCRC patients. How to identify and reverse the secondary resistance to anti-EGFR monoclonal antibody therapy is also another great challenge to improve the anti-EGFR efficacy in wild-type KRAS mCRC patients. Finally, both of the molecular mechanisms of response and acquired resistance would be important for the directions of future research. This review focuses on how to further improve the predictive value of anti-EGFR therapies and how to also try and avoid futile treatment for wild-type KRAS colorectal cancer patients. Keywords: colorectal cancer, EGFR, BRAF, RAS, cetuximab, panitumumab

  3. Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab.

    Science.gov (United States)

    Faratian, Dana; Goltsov, Alexey; Lebedeva, Galina; Sorokin, Anatoly; Moodie, Stuart; Mullen, Peter; Kay, Charlene; Um, In Hwa; Langdon, Simon; Goryanin, Igor; Harrison, David J

    2009-08-15

    Resistance to targeted cancer therapies such as trastuzumab is a frequent clinical problem not solely because of insufficient expression of HER2 receptor but also because of the overriding activation states of cell signaling pathways. Systems biology approaches lend themselves to rapid in silico testing of factors, which may confer resistance to targeted therapies. Inthis study, we aimed to develop a new kinetic model that could be interrogated to predict resistance to receptor tyrosine kinase (RTK) inhibitor therapies and directly test predictions in vitro and in clinical samples. The new mathematical model included RTK inhibitor antibody binding, HER2/HER3 dimerization and inhibition, AKT/mitogen-activated protein kinase cross-talk, and the regulatory properties of PTEN. The model was parameterized using quantitative phosphoprotein expression data from cancer cell lines using reverse-phase protein microarrays. Quantitative PTEN protein expression was found to be the key determinant of resistance to anti-HER2 therapy in silico, which was predictive of unseen experiments in vitro using the PTEN inhibitor bp(V). When measured in cancer cell lines, PTEN expression predicts sensitivity to anti-HER2 therapy; furthermore, this quantitative measurement is more predictive of response (relative risk, 3.0; 95% confidence interval, 1.6-5.5; P biology approach has successfully been used to stratify patients for personalized therapy in cancer and is further compelling evidence that PTEN, appropriately measured in the clinical setting, refines clinical decision making in patients treated with anti-HER2 therapies.

  4. hGBP-1 Expression Predicts Shorter Progression-Free Survival in Ovarian Cancers, While Contributing to Paclitaxel Resistance

    Science.gov (United States)

    Wadi, Suzan; Tipton, Aaron R.; Trendel, Jill A.; Khuder, Sadik A.; Vestal, Deborah J.

    2017-01-01

    Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a tax-ane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer. PMID:28090373

  5. Colorectal cancer cell lines made resistant to SN38-and Oxaliplatin: Roles of altered ion transporter function in resistance?

    DEFF Research Database (Denmark)

    Sandra, Christensen; Jensen, Niels Frank; Stoeckel, Johanne Danmark;

    2013-01-01

    Colorectal cancer (CRC) is the 3rd most common cancer globally, with 5year survival rates of ~50%. Response rates to standard treatments (irinotecan (SN38) or Oxaliplatin (Oxp)) are 31–56% and drug resistance is a major problem. Thus, we established in vitro CRC models to investigate SN38 and Oxp...

  6. Invasive oral cancer stem cells display resistance to ionising radiation.

    Science.gov (United States)

    Gemenetzidis, Emilios; Gammon, Luke; Biddle, Adrian; Emich, Helena; Mackenzie, Ian C

    2015-12-22

    There is a significant amount of evidence to suggest that human tumors are driven and maintained by a sub-population of cells, known as cancer stem cells (CSC). In the case of head and neck cancer, such cells have been characterised by high expression levels of CD44 cell surface glycoprotein, while we have previously shown the presence of two diverse oral CSC populations in vitro, with different capacities for cell migration and proliferation. Here, we examined the response of oral CSC populations to ionising radiation (IR), a front-line measure for the treatment of head and neck tumors. We show that oral CSC initially display resistance to IR-induced growth arrest as well as relative apoptotic resistance. We propose that this is a result of preferential activation of the DNA damagerepair pathway in oral CSC with increased activation of ATM and BRCA1, elevated levels of DNA repair proteins RAD52, XLF, and a significantly faster rate of DNA double-strand-breaks clearance 24 hours following IR. By visually identifying CSC sub-populations undergoing EMT, we show that EMT-CSC represent the majority of invasive cells, and are more radio-resistant than any other population in re-constructed 3D tissues. We provide evidence that IR is not sufficient to eliminate CSC in vitro, and that sensitization of CD44hi/ESAlow cells to IR, followed by secondary EMT blockade, could be critical in order to reduce primary tumor recurrence, but more importantly to be able to eradicate cells capable of invasion and distant metastasis.

  7. Role of XIAP in Therapeutic Resistance in Inflammatory Breast Cancer

    Science.gov (United States)

    2009-07-01

    death receptor-mediated) p athways of a poptosis (3), w hich i s not e vident w ith another pr ominent a nti-apoptotic pr otein B cl-2, which i...tumors of IBC patients. A marked decrease in p- ErbB2, p -ErbB1 and d ownstream s ignaling were e vident i n t he GW583340-resistant c ells (rSUM190 and

  8. Candidaemia and cancer: patients are not all the same

    Directory of Open Access Journals (Sweden)

    Medeiros Lidia

    2006-03-01

    Full Text Available Abstract Background Most of the studies about invasive Candida infections in cancer patients have focused on haematological patients. The aim of this study was to provide information about risk factors for candidaemia in patients with solid tumours. Methods Retrospective cohort study. During a 9-year period (1995–2003 we reviewed all cases of candidaemia that affected cancer patients in Santa Casa Complexo Hospitalar, Brazil. Results During the period of study, 210 patients had the diagnosis of candidaemia in our medical centre, and 83 of these patients had cancer (39.5%. The majority of patients with cancer had solid tumours (77.1%, mostly in the alimentary tract. Most of solid cancers were non-metastatic (71.9%. Major diagnoses in patients with haematological neoplasia were acute leukaemia (n = 13, high grade non-Hodgkin lymphoma (n = 5 and Hodgkin's disease (n = 1. Non-Candida albicans species caused 57.8% of the episodes of candidaemia in patients with cancer, mainly in patients with haematological malignancies (p = 0.034. Neutropenia and treatment with corticosteroids were more frequent in the haematological group, in comparison with patients with solid tumours. Only 22.2% of patients with solid tumours were neutropenic before candidaemia. Nonetheless, the presence of ileus and the use of anaerobicides were independent risk factors for candidaemia in patients with solid cancers. The overall mortality in cancer patients with candidaemia was 49.4%. We then compared 2 groups of adult patients with candidaemia. The first was composed of non-neutropenic patients with solid tumours, and the second group included patients without cancer. We found that central venous catheters and gastrointestinal surgery were independently associated with candidaemia in patients with solid tumour. Conclusion Cancer patients with candidaemia seem to have very different predisposing factors to acquire the infection when stratified according to baseline diseases

  9. Symptom monitoring in treatment of cancer patients

    Institute of Scientific and Technical Information of China (English)

    Yao Wanxia; Lin Miao; Lü Ye; Yang Biao; Yao Cong; Liu Juan; Wang Wenru

    2008-01-01

    Objective To examine self-reported symptoms by the patients receiving cancer therapy, and find out the symptoms that should be coped with and managed during the treatment. Methods A pilot study was conducted on self-reported symptoms on 185 patients receiving chemotherapy and/or radiotherapy for different cancers. The Therapy-Related Symptoms Checklist (TRSC) was used. Results Severe symptoms on the TRSC subscales: loss of appetite,feeling sluggish, weight loss, nausea and hair loss, were reported by the patients. The frequently reported symptoms by those on chemotherapy were nausea, feeling sluggish, weight loss, vomiting, and taste change. The frequently reported symptoms by those on radiotherapy were feeling sluggish, weight loss, loss of appetite, difficult sleeping, and changing taste. The symptoms of loss of appetite, feeling sluggish, weight loss, hair loss, and nausea were both frequently reported by those on radiotherapy and those on chemotherapy. Conclusion Symptom monitoring may be facilitated by TRSC, based on the severity and frequency of reported symptoms, more patients and caregivers could know which symptoms should be preferential interventions.

  10. Clinicopathologic characteristics of young patients with gallbladder cancer.

    Science.gov (United States)

    Do, Sung-Im; Lee, Hyoun Wook; Sohn, Jin Hee; Kim, Kyungeun

    2017-03-01

    Gallbladder cancer is the most common biliary tract cancer and the fifth most common cancer of the digestive system. However, the clinicopathologic features of gallbladder cancer in young Korean patients have not been studied. This study included 101 consecutive cases of gallbladder cancer that underwent cholecystectomy at Kangbuk Samsung Hospital from December 1990 to March 2011. The patients were divided into two groups by age at initial diagnosis of gallbladder cancer: a young patient group aged less than 45 years and an old patient group aged 45 or older. The young patient group included 10 patients with mean age of 38 (range, 29-44 years). Compared with the old patient group, the young patient group showed polypoid tumor appearance (p=0.014), lower pT stage (p=0.023), more frequent adenoma background (p=0.009), and less frequent dysplasia in remaining mucosa (p=0.001). The disease-related survival rate after 13.5 months was significantly more favorable for the young patients. Gallbladder cancers in young Korean patients have distinct clinicopathologic features of a high frequency of cancer arising in adenoma, rare association with intestinal metaplasia and dysplasia, and a favorable patient's prognosis. These findings suggest that the adenoma-carcinoma pathway could contribute more to gallbladder cancer carcinogenesis in young Korean patients than the metaplasia-dysplasia-carcinoma pathway.

  11. The mass media and the cancer patient--some views.

    Science.gov (United States)

    Rimer, I

    1984-01-01

    A study by the National Cancer Institute indicates extensive newspaper coverage of the subject of cancer. Some of the media presentations on cancer are highly emotional in nature, such as the PBS special, "Joan Robinson: One Woman's Story." Other more optimistic stories may have a negative impact on patients facing more advanced stages of the disease. Yet the media appear to be gradually stripping the mystery from cancer and preparing patients to deal with their treatment and physicians more intelligently and more assertively. Breast and lung cancers are the two sites that get the most attention from the press. Unfortunately, colon and rectum cancers rank quite low in press attention. The American Cancer Society (ACS) has studied public attitudes toward these cancers and is preparing programs to reach the public about them. This paper will deal with these topics and make some observations on the impact of