Klughammer B.,Hoffmann-La Roche |
Brugger W.,Albert Ludwigs University of Freiburg |
Cappuzzo F.,Instituto Toscano Tumori |
Ciuleanu T.,Prof Dr Ion Chiricuta Institute Of Oncology |
And 11 more authors.
Journal of Thoracic Oncology | Year: 2016
Introduction: Exon 19 deletions and the exon 21 L858R mutation of the epidermal growth factor receptor gene (EGFR) predict activity of EGFR tyrosine kinase inhibitors, including erlotinib; however, the ability of less common EGFR mutations to predict efficacy of erlotinib is unclear. Methods: The efficacy of erlotinib in individual patients with rare EGFR mutations from the MERIT, SATURN, TITAN, TRUST, ATLAS, BeTa, and FASTACT-2 trials was analyzed and compared with data from the literature. Results: In the patients tested for biomarkers, the frequency of rare mutations identified here ranged from 1.7% (eight of 467) in the SATURNstudy to 7.4%(27 of 364) in ATLAS. Some rare mutations were associated with greater clinical benefit from EGFR tyrosine kinase inhibitor therapy or improved prognosis independent of treatment,whereas others appeared to have a poorer prognosis. In particular, exon 18 G719 mutations, exon 19 K757R and E746G mutations, the exon 20 S768Imutation, and the exon 21 G836Smutation appeared to confer a good outcome with erlotinib treatment,whereas exon 18 S720I showed a particularly poor outcome. Owing to the small number of patients with each mutation, however, it is difficult to confirm whether these rare mutations do indeed confer sensitivity or resistance to erlotinib. Conclusions: Erlotinib can have different efficacy depending on the specific EGFR mutation. More research is needed to create a central database such as the My Cancer Genome database of rare mutations to definitively confirm whether these mutations are activating, resistant, or neutral. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
PubMed | The Ottawa Hospital Cancer Center, Prof Dr Ion Chiricuta Institute Of Oncology, University of Sarajevo, McGill University and 11 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017
CRA8007 Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity.Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/mEnrollment of 255 adenocarcinoma patients completed in November 2012; results are reported for this population. Patient characteristics were balanced (median age 60 years, males ~60%, PS 0 ~40% and never-smoker ~25%). For D+G vs. D the median number of cycles delivered was 5 vs. 4; the grade 3/4 adverse events were neutropenia 38% vs. 37%; fatigue 4% vs. 3%; anemia 7% vs. 6%; diarrhea 3% vs. 0; fever with neutropenia 8% vs. 2%. At the time of abstract submission OS HR was 0.69 (90% CI 0.48 to 0.99, p=0.093), the PFS HR was 0.70 (90% CI 0.53 to 0.94, p=0.012), and the ORR was 15% vs 11%, favoring D+G. For patients that were enrolled >6 months after diagnosis of advanced NSCLC (N=175; 69%), a prespecified stratification factor, the OS HR was 0.41 (90% CI 0.25 to 0.67, p=0.0009), the PFS HR was 0.47 (90% CI 0.32 to 0.69, p=0.0005), and the ORR was 16% vs 12%. Updated results for both populations above, as well as for the eLDH and mKRAS subsets, will be presented.D+G demonstrated improvement in OS, PFS, and ORR over D alone for second-line therapy of lung adenocarcinoma. A phase III study in second-line advanced adenocarcinoma patients (> 6 months from diagnosis) is ongoing (GALAXY-2).NCT01348126.
PubMed | University of America, University of Medicine and Pharmacy, Cluj-Napoca, Cyprus University of Technology, Archbishop Makarios III Hospital and Prof Dr Ion Chiricuta Institute Of Oncology
Type: Journal Article | Journal: PloS one | Year: 2016
Although the increasing prevalence of thyroid nodular disease (TND) has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (ClxBPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter >3mm), and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and ClxBPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression. Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%), the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified.
PubMed | Phoenix Diagnostic Clinic, University of Medicine and Pharmacy, Cluj-Napoca, Octavian Fodor Institute of Gastroenterology and Hepatology and Prof Dr Ion Chiricuta Institute Of Oncology
Type: Case Reports | Journal: Journal of medical ultrasonics (2001) | Year: 2015
Neuroendocrine carcinoma of the gallbladder is an uncommon disease. We present the case of a 45-year-old woman with a mass located in the gallbladder, whose diagnosis was based on contrast-enhanced ultrasound and magnetic resonance imaging. The tumor involved the liver and retroperitoneum, and was histopathologically confirmed by liver biopsy as a neuroendocrine tumor grade 3. The patient received chemotherapy with good response, followed by surgery with cholecystectomy and partial hepatectomy.
Bochis O.V.,Prof Dr Ion Chiricuta Institute Of Oncology |
Bochis O.V.,University of Medicine and Pharmacy, Cluj-Napoca |
Irimie A.,Prof Dr Ion Chiricuta Institute Of Oncology |
Irimie A.,University of Medicine and Pharmacy, Cluj-Napoca |
And 5 more authors.
Journal of Gastrointestinal and Liver Diseases | Year: 2015
Colorectal cancer is one of the most frequent cancers worldwide, having the fourth mortality rate among cancers in both sexes. Numerous studies are investigating the signaling pathways and different factors involved in the development and progression of colorectal cancer. It has recently been shown that the S-phase kinaseassociated protein 2 (Skp2) overexpression plays an important role in the pathogenesis of colorectal cancer. We review the role of Skp2 and its ubiquitin-proteasome pathway in colorectal cancer. The F-box protein Skp2, a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex, has been shown to regulate cellular proliferation, cancer progression and metastasis by targeting several cell cycle regulators for ubiquitination and subsequent 26S proteasome degradation. The best known protein substrate of the Skp2 is the cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27Kip1. Overexpression of Skp2 and loss of CDKN1B (p27) was strongly associated with aggressive tumor behavior and poor clinical outcome in a variety of cancers, including colorectal cancer. An efficient interaction between Skp2 and CDKN1B (p27) requires the presence of an essential activator of the SCF-Skp2 complex, the cyclin-dependent kinase subunit 1 (Cks1) cofactor. Alterations in the Skp2, Cks1 and CDKN1B (p27) expression have major effects on colorectal carcinogenesis and may serve as an important and independent prognostic marker. Furthermore, we highlight that Skp2 may be a promising therapeutic target for colorectal cancer, and development of Skp2 inhibitors would have a great impact on colorectal cancer therapy. © 2015 Romanian Society of Gastroenterology. All rights reserved.
Bondarenko I.M.,Dnepropetrovsk Medical Academy |
Ingrosso A.,Pfizer |
Bycott P.,Pfizer |
Kim S.,Pfizer |
Cebotaru C.L.,Prof Dr Ion Chiricuta Institute Of Oncology
BMC Cancer | Year: 2015
Background: Axitinib is an orally active and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. This phase II study assessed the efficacy and safety of axitinib combined with cisplatin/gemcitabine in chemotherapy-naïve patients with advanced/metastatic (stage IIIB/IV) squamous non-small-cell lung cancer (NSCLC). Methods: Axitinib (starting dose 5 mg twice daily [bid]; titrated up or down to 2-10 mg bid) was administered orally on a continuous schedule with cisplatin (80 mg/m2 intravenously [i.v.] every 3 weeks) and gemcitabine (1,250 mg/m2 i.v. on days 1 and 8 of each 3-week cycle), and was continued as monotherapy after completion of six cycles (maximum) of chemotherapy. The primary study endpoint was objective response rate, as defined by Response Evaluation Criteria in Solid Tumours. Results: Of the 38 patients treated, one (2.6%) patient achieved a complete response and 14 (36.8%) patients had a partial response; nine (23.7%) patients showed stable disease and three (7.9%) patients had disease progression. Median progression-free survival was 6.2 months, and median overall survival was 14.2 months. The estimated probability of survival at 12 months and 24 months was 63.2% and 30.8%, respectively. The most frequent grade ≥3 toxicities were neutropaenia and hypertension (13.2% each). Three (7.9%) patients experienced haemoptysis, of which one case (2.6%) was fatal. Conclusions: Treatment with the combination of axitinib and cisplatin/gemcitabine demonstrated anti-tumour activity in patients with advanced/metastatic squamous NSCLC and the fatal haemoptysis rate was low. However, without a reference arm (cisplatin/gemcitabine alone), it is not conclusive whether the combination is better than chemotherapy alone. This study was registered at ClinicalTrials.gov, registration NCT00735904, on August 13, 2008. © 2015 Bondarenko et al.
Maxim M.A.,University of Medicine and Pharmacy, Cluj-Napoca |
Soritau O.,Prof Dr Ion Chiricuta Institute Of Oncology |
Baciut M.,University of Medicine and Pharmacy, Cluj-Napoca |
Bran S.,University of Medicine and Pharmacy, Cluj-Napoca |
Baciut G.,University of Medicine and Pharmacy, Cluj-Napoca
Clujul Medical | Year: 2015
Mesenchymal stem cells (MSCs) are adult stem cells that have the capacity of rising multiple cell types. A rich source of mesenchymal stem cells is represented by the dental tissues: the periodontal ligament, the dental pulp, the apical papilla, the dental follicle and the deciduous teeth. The aim of this review is to characterize the main dental- derived mesenchymal stem cell population, and to show their important role in tissue regeneration based on their properties: the multi-potency, the high proliferation rate, the differentiation in multiple cell lineages, the high cell viability and the positive expression for mesenchymal cell markers. Tissue regeneration or de novo' formation of craniofacial structures is the future of regenerative medicine, offering a solution for congenital malformations, traumas and other diseases.
Lupse M.,University of Medicine and Pharmacy, Cluj-Napoca |
Flonta M.,Teaching Hospital of Infectious Diseases |
Cioara A.,University of Medicine and Pharmacy, Cluj-Napoca |
Filipescu I.,University of Medicine and Pharmacy, Cluj-Napoca |
Todor N.,Prof Dr Ion Chiricuta Institute Of Oncology
Journal of Gastrointestinal and Liver Diseases | Year: 2013
Background & Aims: Clostridium difficile is recognized as the major cause of nosocomial gastroenteritis usually related to antibiotic treatment. Although treatable, C. difficile - associated disease (CDAD) tends to recur in many patients. The purpose of the study was to analyze the risk factors for recurrence in patients with CDAD after the first treatment with vancomycin, metronidazole or both. Method: We conducted a retrospective study of all patients admitted to the Teaching Hospital of Infectious Diseases Cluj-Napoca, Romania, between January 2011 and October 2012 with the diagnosis of CDAD or who developed diarrhoea after admission. A clinical diagnosis was made and culture and toxin A and B detection were carried out. We performed a statistical analysis taking into consideration: age, gender, previous hospital exposure, previous antibiotic treatment, and treatment duration. The patients were followed-up for at least 60 days. Results: We included 306 patients (177 women and 129 men) with a median age of 71 years; 208 patients (68%) had prior hospitalization and 195 (64%) had received prior antibiotic treatment. Actual treatment consisted of vancomycin in 76 (25%) patients, metronidazole in 132 (43%) and both combined in 98 (32%) patients. The average duration of treatment was 10 days. Sixty patients (20%) experienced 95 recurrences and 9 patients died (3%). Treatment with metronidazole, vancomycin or both for 10 or more days did not prevent recurrences. Age over 70 (RR 1.5, CI 95%: 1.055-2.71) and use of PPI (RR 1.3, CI 95%: 1.16-3.1) significantly increased the risk of first recurrence of CDAD. Conclusions: CDAD recurrence rates were similar to those reported in the literature. The risk of first recurrence was significantly higher in patients older than 70 who also received PPI treatment.
PubMed | Prof Dr Ion Chiricuta Institute Of Oncology
Type: Clinical Trial, Phase II | Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology | Year: 2016
The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen.Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonalds trial.In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonalds trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS.The proposed treatment is not less effective compared with the McDonalds trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.
PubMed | Prof Dr Ion Chiricuta Institute Of Oncology
Type: Journal Article | Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology | Year: 2015
Tumor angiogenesis is regarded as a hallmark of cancer and provides an important target for therapy. Nestin is an intermediate filament protein (IF) originally recognized as a neural stem cell marker. Development and progression of cancer requires sustained angiogenesis, dependent on the proliferation and migration of endothelial cells which seem to be better portrayed by nestin expression in various malignancies such as central nervous system, gastro-intestinal cancers, malignant melanoma, lung, prostate or breast cancer. The purpose of the present review was to emphasize the insights into nestin expression in relation to tumor angiogenesis in different types of cancer. Current evidence suggests that nestin positivity in tumor cells reflects stem-like properties of those cells. Whether or not expressed in both tumor and endothelial cells, nestin overexpression might reflect the extent of angiogenesis and function as a molecular anti-angiogenic target for cancer.