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Kraków, Poland

Pritchard K.I.,University of Toronto | Rolski J.,Oncological Institute | Papai Z.,State Health Center | Mauriac L.,Institute Bergonie | And 9 more authors.
Breast Cancer Research and Treatment | Year: 2010

The Faslodex Investigation of Dose evaluation in Estrogen Receptor-positive advanced breast cancer (FINDER)2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of three fulvestrant dosing regimens. FINDER2 enrolled Western postmenopausal women recurring or progressing after prior endocrine therapy. Primary endpoint: objective response rate (ORR); secondary endpoints: time to progression (TTP), clinical benefit rate (CBR), tolerability, and PK parameters. Patients were randomized to receive fulvestrant: 250 mg/month (approved dose [AD]); 250 mg plus loading dose (loading dose [LD]; 500 mg on day 0, 250 mg on days 14, 28, and monthly thereafter); or 500 mg (high dose [HD]; 500 mg/month plus 500 mg on day 14 of Month 1). Treatment continued until disease progression or discontinuation. 144 patients were randomized: fulvestrant AD (n = 47); LD (n = 51); HD (n = 46). ORRs were: 8.5% (95% confidence interval [CI]: 2.4, 20.4%), 5.9% (1.2, 16.2%), and 15.2% (6.3, 28.9%) in the AD, LD, and HD arms, respectively. CBRs were: 31.9% (95% CI: 19.1, 47.1%), 47.1% (32.9, 61.5%), and 47.8% (32.9, 63.1%) for the AD, LD, and HD arms, respectively. Median TTP (months) was numerically longer for HD (6.0) and LD (6.1) versus AD (3.1). Tolerability was similar across dosing regimens. Steady-state plasma fulvestrant concentrations were predictable and achieved earlier with LD and HD. While there appeared to be a trend toward improved efficacy with HD and LD versus AD, no significant differences could be shown. A parallel study (FINDER1) has reported similar findings in Japanese patients. © 2010 Springer Science+Business Media, LLC. Source

Pinton P.,French National Institute for Agricultural Research | Braicu C.,French National Institute for Agricultural Research | Braicu C.,Oncological Institute | Nougayrede J.-P.,French National Institute for Agricultural Research | And 4 more authors.
Journal of Nutrition | Year: 2010

Deoxynivalenol (DON) is a common mycotoxin that contaminates cereals and their by-products. The gastrointestinal tract is the first physical barrier against ingested food contaminants. DON contributes to the loss of barrier function of the intestine through the decreased expression of claudin-4 protein, a tight junction protein. The mechanism by which DON alters the intestinal barrier function remains poorly characterized. Therefore, we investigated the involvement of mitogen-activated protein kinases (MAPK) in the DON-induced loss of barrier function. We first verified that 30 μmol/L of DON activated MAPK in a highly sensitive porcine intestinal epithelial cell line (IPEC-1). Inhibition of p44/42 extracellular signal-regulated kinase (ERK) phosphorylation, with 0.5 μmol/L of the specific MAPK pharmacological inhibitor U0126 for 2 h, restored the barrier function of the differentiated intestinal epithelial cell monolayers. The restoration of barrier function was evaluated by trans-epithelial electrical resistance measurements and tracer flux paracellular permeability experiments. The U0126 also restored the intestinal expression of claudin-4 protein, thereby demonstrating that MAPK activation is involved in claudin-4 protein expression and claudin-4 is involved in the maintenance of the intestinal epithelial cell barrier function. Further experiments indicated that p44/42 ERK is not involved in the transcriptional regulation of claudin-4. In conclusion, we demonstrated that DON-induced activation of the p44/42 ERK signaling pathway inhibits the expression of claudin-4 protein, which leads to impaired intestinal barrier function. Given the high levels of DON in cereal grains, these observations of impaired barrier function have implications for human and animal health. © 2010 American Society for Nutrition. Source

Grigore M.,Grigore T. Popa University of Medicine and Pharmacy | Ilea C.,Grigore T. Popa University of Medicine and Pharmacy | Terinte C.,Oncological Institute | Sava A.,Grigore T. Popa University of Medicine and Pharmacy | Popovici R.,Grigore T. Popa University of Medicine and Pharmacy
European Journal of Gynaecological Oncology | Year: 2014

Carcinosarcoma is a rare, extremely aggressive tumor of the uterus with a poor prognosis. The authors describe a case of a 78-year-old woman who presented with a giant mass protruding through the cervix, vagina, and vulva. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological examination of the surgical specimen revealed a malignant mixed Müllerian tumor. The clinical and pathological features, molecular data, and prognosis of this aggressive neoplasm are discussed. Although uterine carcinosarcomas are extremely rare, when a postmenopausal woman with a vulvar mass is admitted to the gynecology clinic, the physician should consider that the mass may be a carcinosarcoma. Source

Amit M.,Technion - Israel Institute of Technology | Ilana K.,Tel Aviv Medical Center | Avraham S.P.,Tel Aviv Medical Center | Binenbaum Y.,Technion - Israel Institute of Technology | And 8 more authors.
Head and Neck | Year: 2016

Background The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. Methods The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Results Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p <.02). Conclusion This study demonstrated a rate of HPV-related oropharyngeal SCC in Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc.. Source

Netzer I.,Gynecological Oncology Unit | Sobeh S.,Technion - Israel Institute of Technology | Keidar Z.,Technion - Israel Institute of Technology | Lowenstein L.,Gynecological Oncology Unit | And 5 more authors.
Medical Oncology | Year: 2013

Cervical cancer is one of the leading causes of death among women with gynecological malignancies. In early stages of the disease (IB-IIA), surgical treatment alone is usually the treatment of choice. However, some high-risk patients are referred for postoperative chemo-radiotherapy, leading to increased morbidity. Maximal Standardized Uptake Value (SUVmax) is a positron emission tomography-computed tomography (PET-CT)-derived semiquantitative measurement of fluorodeoxyglucose (FDG) uptake in a defined lesion and may reflect tumor aggressiveness. The purpose of this study was to determine whether preoperative high SUVmax values can be used for the selection of initial therapy, thus reducing the side effects resulting from bimodal treatment. PET-CT studies of 46 cervical cancer patients who underwent surgery were reviewed, and SUVmax data were collected. Statistical analyses were performed to determine the relationships between SUVmax values and clinical parameters, modalities of treatment, and outcomes. SUV max was found to correlate with depth of tumor invasion (r = 0.46, p < 0.003). A statistically significant correlation was also found between SUVmax and histological grade, with the mean and variance of SUV max significantly lower for grade one, as compared to grades two and three (mean 1.10, 11.06, and 8.88; variance 3.57, 45.60, and 29.79, respectively; p < 0.0001 and p = 0.076). A possible SUVmax cutoff value of 10.08 was identified as a potential indicator of increased risk for receiving bimodal treatment, with a sensitivity of 61.5 % and a specificity of 75.8 %. SUVmax can be used for differentiating early-stage cervical cancer patients who will need postoperative adjuvant treatment and therefore can serve as an additional modality to reduce the need for bimodal therapy in these patients. © 2013 Springer Science+Business Media New York. Source

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