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Ymittos Athens, Greece

Florou D.,National and Kapodistrian University of Athens | Patsis C.,National and Kapodistrian University of Athens | Patsis C.,Lady Davis Institute for Medical Research | Ardavanis A.,St. Savas Anticancer Hospital | Scorilas A.,National and Kapodistrian University of Athens
Cancer Biology and Therapy | Year: 2013

Defective apoptosis comprises the main reason for tumor aggressiveness and chemotherapy tolerance in solid neoplasias. Among the BCL-2 family members, whose mRNA or protein expression varies considerably in different human malignancies, BCL2L12 is the one for which we have recently shown its propitious prognostic value in gastric cancer. The purpose of the current work was to investigate the expression behavior of BCL2L12, BAX and BCL-2 in human stomach adenocarcinoma cells following their exposure to antitumor substances. The 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue methods assessed the impact of doxorubicin, oxaliplatin and methotrexate on AGS cells' viability and growth. Following isolation from cells, total RNA was reverse-transcribed to cDNA. Quantification of target genes' expression was performed with real-time PCR using SYBR Green detection system. The relative changes in their mRNA levels between drug-exposed and untreated cells were calculated with the comparative Ct method (2-ddCt). All three drugs, as a result of their administration to AGS cancer cells for particular time intervals, provoked substantial fluctuations in the transcriptional levels of the apoptosis-related genes studied. While BAX was principally upregulated, striking similar were the notable changes regarding BCL-2 and BCL2L12 expression in our cellular system. Our findings indicate the growth suppressive effects of doxorubicin, oxaliplatin and methotrexate treatment on stomach carcinoma cells and the implication of BCL2L12, BAX and BCL-2 expression profiles in the molecular signaling pathways triggered by chemotherapy. © 2013 Landes Bioscience. Source

Baltatzis G.E.,Research Center panikolaou | Voloudakis G.E.,Research Center panikolaou | Arnogiannakis N.,St. Savas Anticancer Hospital | Misitzis J.,St. Savas Anticancer Hospital | Voloudakis-Baltatzis I.E.,Research Center panikolaou
Ultrastructural Pathology | Year: 2011

The tubular carcinoma of the breast is an uncommon histological subtype of invasive breast cancer, which is generally associated with an excellent prognosis. Previous studies have demonstrated that this well differentiated variant is linked with a low incidence of lymph node involvement, a low rate of local recurrence and a high overall survival rate when compared to standard invasive ductal carcinoma. Due to its favorable prognosis, some studies have proposed that a diagnosis of tubular carcinoma might warrant less aggressive surgical or adjuvant treatment. Histologically, tubular carcinoma may mimic sclerosing adenoma or bluntduct adenosis. Its ductal nature appears well confirmed by the few ultrastructural studies of this mammary cancer. Tubular carcinoma should also be distinguished from microglandular adenosis, an uncommon form of sclerosing adenosis. The aim of this study is to prove that the ultrastructure results can give the correct diagnosis between tubular carcinoma and sclerosing adenosis. © 2011 Informa Healthcare USA, Inc. Source

Baltatzis G.E.,Research Center panikolaou | Gaitanarou H.,Research Center panikolaou | Arnogianaki N.,St. Savas Anticancer Hospital | Misitzis J.,St. Savas Anticancer Hospital | Voloudakis-Baltatzis I.E.,Research Center panikolaou
Ultrastructural Pathology | Year: 2011

Mucinous infiltrating invasive ductal adenocarcinoma consists of 2-4% invasive breast cancer, but is a very interesting type due to its macroscopic similarity to non-special-type (NST) ductal carcinoma. The macroscopic similarity of mucinous and infiltrating ductal carcinoma NST adenocarcinomas consists of a loose and edematous stroma, which is often seen in portions of NST carcinoma and may mimic the mucin pools of mucinous carcinoma. In this study the authors examined the ultrastructural differences between mucinous carcinoma and infiltrating ductal carcinoma NST. They also examined the protein expression of the tissues by 2D electrophoresis due to their belief that from the results of these two levels it is possible to understand the changes that take place both in the ultrastructural and biochemical levels in these two types of breast cancer. The ultrastructural results from mucinous carcinoma have shown many changes in cytoplasmic organelles in comparison to normal samples, depending on the grade and the number of metastatic lymph nodes. At the 2D elecrophoresis level the authors studied two interesting polypeptides, calreticulin and thioredoxin. Both of these proteins were found in patterns of fibroadenoma, mucinous carcinoma, and NST carcinoma, but with different quantitative expression among them. In the future the quantitative differences of these two proteins may provide specific tumor markers for these two types of carcinoma. Copyright © 2011 Informa Healthcare USA, Inc. Source

Kountourakis P.,St. Savas Anticancer Hospital | Missitzis I.,St. Savas Anticancer Hospital | Doufexis D.,St. Savas Anticancer Hospital | Zobolas V.,St. Savas Anticancer Hospital | And 5 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011

Background: Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine-vinorelbine (GEV) peri-operatively in LABC. Patients and methods: Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100 mg/m2, d1q2w) followed by three DOC (100 mg/m2, d1q3w); surgery 3-4 weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR). Results: Fifty-six women, aged 32-75 (median 52 years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. Efficacy: clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62 months, median OS has not yet been reached, while median TTR was 42 months. OS was longer in patients with clinical (p = 0.004) and pathological response (p = 0.002), RT (p < 0.0001) and post-operative DOC (p = 0.038). TTR was favorably affected by pR (p < 0.0001), RT (p < 0.0004) and post-operative DOC (p = 0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status. Conclusion: The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management. © 2010 Springer-Verlag. Source

Kountourakis P.,St. Savas Anticancer Hospital | Doufexis D.,St. Savas Anticancer Hospital | Maliou S.,St. Savas Anticancer Hospital | Karagiannis A.,St. Savas Anticancer Hospital | And 5 more authors.
Anticancer Research | Year: 2010

Background: Metastatic breast cancer remains a major clinical issue despite progress achieved in recent years. Three randomised trials have demonstrated the benefit of combining bevacizumab with various taxane schedules. Herein, this study sought to investigate an alternative bevacizumab-taxane regimen as first-line treatment for metastatic breast cancer. Patients and Methods: Patients with metastatic breast cancer and who received first-line bevacizumab 10 mg/kg with paclitaxel 135 mg/m2 every 2 weeks were studied. Results: All 43 enrolled patients were evaluable for efficacy and safety. The response rate was 58%; a further 40% achieved stable disease. After a median follow-up of 16 months, disease had progressed in 9 patients (21%). Treatment was well tolerated: grade 4 toxicities were absent; grade 3 adverse events comprised neutropenia (5%; no febrile neutropenia), hypertension (2%) and neuropathy (2%). Conclusion: This regimen may provide improved patient acceptability, quality of life and pharmacoeconomic benefits over a weekly paclitaxel schedule, and deserves further evaluation. Source

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