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Oikonomopoulos G.M.,St Savvas Anticancer Hospital | Syrigos K.N.,National and Kapodistrian University of Athens | Skoura E.,Evaggelismos General Hospital | Saif M.W.,Tufts Medical Center
Journal of the Pancreas | Year: 2014

In the field of treatment of pancreatic cancer, there has been significant progress lately. After the ACCORD/PRODIGE-4 study, 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) became the standard combination for first-line chemotherapy. This led also to its use in the neoadjuvant setting in borderline resectable tumors, or locally advanced unresectable disease, improving the resectability and survival. The major disadvantage of this therapy is increased toxicity, limiting its use to young patients with no comorbidities. This arises the need to make dose reductions in clinical practice, with a possible drawback in effectiveness. The authors summarize three Abstracts (#256, #275, #305) presented at the 2014 ASCO Gastrointestinal Cancers Symposium which were focused in the use of modified forms of FOLFIRINOX, their toxicity profile and effectiveness. Reduced toxicity was observed, without affecting the effectiveness of the combination.

Tzifi F.,National and Kapodistrian University of Athens | Tzifi F.,Aghia Sophia Childrens Hospital | Economopoulou C.,Rimini Street | Gourgiotis D.,National and Kapodistrian University of Athens | And 3 more authors.
Advances in Hematology | Year: 2012

The disturbance of apoptosis molecular signaling pathways is involved in carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation. In the last decade, new members of BCL2 gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. It is well known that leukemias are haematopoietic malignancies characterized by biological diversity, varied cytogenetics, different immunophenotype profiles, and diverse outcome. Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. The understanding of the molecular pathways that participate in the biology of leukemias may lead to the design of new therapies which may improve patients' survival. In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias. Copyright © 2012 Flora Tzifi et al.

Michaelidou K.,National and Kapodistrian University of Athens | Tzovaras A.,St Savvas Anticancer Hospital | Missitzis I.,St Savvas Anticancer Hospital | Ardavanis A.,St Savvas Anticancer Hospital | Scorilas A.,National and Kapodistrian University of Athens
International Journal of Oncology | Year: 2013

Breast cancer (BC) continues to affect the lives of millions of women worldwide. Several members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) subfamily are involved in tumor progression. Notably, the CEACAM subfamily harbors the already established cancer biomarker CEA, as well as other potential molecular markers. CEACAM19, a recently identified gene belonging to CEACAM subfamily, was discovered and cloned by members of our research group. The present study analyzes, quantitatively, the expression of CEACAM19 and evaluates its clinical relevance in BC. Total RNA was extracted from 143 cancerous and 89 normal adjacent breast tissue specimens. Following reverse transcription, quantitative analysis of CEACAM19 mRNA expression levels was performed via real-time PCR and the comparative Ct (2 -ΔΔCt) method. CEACAM19 expression and detailed clinicopathological data were used for extensive biostatistical analyses. CEACAM19 was found to be overexpressed in breast cancer tissue specimens compared to normal tissue counterparts (p=0.013). CEACAM19 mRNA expression status was also associated with clinicopathological features indicative of aggressive behavior and poor prognosis in BC, such as high tumor grade (p=0.031) and high Ki67 proliferative index (p=0.038). A significant negative association was documented between CEACAM19 expression and tumor ER status (p=0.018) as well as patients' menopausal state (p=0.016). Our results suggest that CEACAM19 mRNA expression represents a promising, novel and clinically useful tissue biomarker for breast cancer management.

Michaelidou K.,National and Kapodistrian University of Athens | Ardavanis A.,St Savvas Anticancer Hospital | Scorilas A.,National and Kapodistrian University of Athens
Breast Cancer Research and Treatment | Year: 2015

Examining for new BC biomarkers has proven that kallikrein-related peptidase (KLK) family members represent promising serum and/or tissue molecular tools for early diagnosis, effective prognosis, and treatment monitoring of patients. The aim of this study was to investigate, the previously unexplored, prognostic significance of KLK8 in BC. KLK8 mRNA expression was quantitatively analyzed in 150 cancerous and 100 corresponding normal breast tissue specimens via a SYBR Green-based Real-Time PCR methodology. Expression data and patients’ clinicopathological parameters were used for extensive biostatistical analyses, including internal validation. KLK8 mRNA expression was significantly downregulated in the cancerous tissue part relative to the non-cancerous counterpart (P < 0.001), in the majority of the paired breast tissue samples. KLK8 expression was associated with advanced TNM stage (P = 0.019) and positive nodal status involvement (P = 0.044). Triple negative (TNBC) and HER2 overexpressing tumors exhibited higher KLK8 expression levels (P < 0.001), compared to Luminal A and B molecular subtypes. Kaplan–Meier survival curve analysis revealed that BC patients with high KLK8 expression had significantly shorter disease-free survival (DFS) intervals (P < 0.001) compared to those belonging in the KLK8-low expression group. Cox univariate analysis confirmed the association between KLK8 expression, analyzed as a continuous variable, and poor patients’ outcome (Hazard ratio [HR] = 3.28, P < 0.001). Most importantly, multivariate analysis showed that KLK8 expression is a strong and independent predictor of adverse DFS in BC ([HR] = 2.74; P = 0.002). Our results show that KLK8 mRNA expression is associated with aggressive tumor characteristics and it can serve as a novel independent biomarker of unfavorable prognosis for BC patients. © 2015, Springer Science+Business Media New York.

Oikonomopoulos G.M.,St Savvas Anticancer Hospital | Huber K.E.,Tufts Medical Center | Syrigos K.N.,National and Kapodistrian University of Athens | Saif M.W.,Tufts Medical Center
Journal of the Pancreas | Year: 2013

Treatment of locally advanced pancreatic cancer is palliative, based on chemotherapy and according to response, chemoradiotherapy can be applied. The authors summarize three abstracts (#LBA146, #256 and #303) presented on the 2013 ASCO Gastrointestinal Cancers Symposium, which were focused on treatment of locally advanced pancreatic cancer. A discussion is presented about the different chemotherapy or chemoradiotherapy regimens, that move away from gemcitabine-based treatment, and the effort to find less toxic, but efficient therapeutic combinations.

Oikonomopoulos G.M.,St Savvas Anticancer Hospital | Syrigos K.N.,Sotiria General Hospital | Wasif Saif M.,Tufts Medical Center
Journal of the Pancreas | Year: 2013

Pancreatic cancer is a frequent and lethal disease ranking fourth as a cause of cancer-related death in Western countries. There are patients, though, who respond well to chemotherapy and have a prolonged survival. There is an effort towards identification of specific characteristics of these tumor cells in order to identify those patients who will benefit from chemotherapy and use them as prognostic or predictive factors. This review is an update on the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting regarding the most important developments in this field for pancreatic cancer, as they were reported in Abstracts #4006, #4016, #4046, and #4060 and a discussion is presented about their application in clinical praxis.

Dimitriadis E.,St Savvas Anticancer Hospital | Kalogeropoulos T.,St Savvas Anticancer Hospital | Velaeti S.,St Savvas Anticancer Hospital | Sotiriou S.,University of Ioannina | And 7 more authors.
Anticancer Research | Year: 2013

Background: Early diagnosis of prostate cancer and identification of new prognostic factors remain main issues in prostate cancer research. In this study, we sought to test a panel of cancer-specific markers in urine samples as an aid for early cancer diagnosis. Materials and Methods: Sedimented urine samples of 66 candidates for needle biopsy were tested. Real time-polymerase chain reaction (RT-PCR) was applied to detect the expression of transmembrane protease serine-2 and Ets-related gene fusion (TMPRSS2-ERG), Ets-related gene (ERG), prostate cancer antigen-3 (PCA3), and serine peptidase inhibitor kazal type-1 (SPINK1) transcripts. For testing of the methylation status of Glutahione S-tranferase P (GSTP1) and Ras association domain family member-1(RASSF1A) promoter region, methylation-specific PCR (MSP-PCR) was applied. Results: Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer. A multivariable logistic regression including all the significantly associated variables [prostate-specific antigen (PSA), digital rectal examination (DRE), TMPRSS2-ERG and PCA3], yielded a model with area under the receiver-operating characteristic curve (AUC) =0.894 (95% CI=0.772-1.00). Conclusion: A multiplexed quantitative PCR analysis on sedimented urine, in conjunction with the results of serum PSA levels and DRE, has the potential to accurately foresee subsequent needle biopsy outcomes. On the basis of the above, algorithms may be designed to guide decisions for needle biopsy.

Orphanos G.,Ygia Polyclinic | Ardavanis A.,St Savvas Anticancer Hospital
Clinical and Experimental Metastasis | Year: 2010

Leptomeningeal metastases from solid tumors are relatively uncommon events with dismal prognosis. They can be seen mainly in patients with breast and lung cancer, and malignant melanoma, but have also been described in a variety of other tumor types. Leptomeningeal carcinomatosis from prostate cancer is an extremely rare complication, but as patients' survival is prolonged due to more effective treatments, it is expected that more patients will present with leptomeningeal involvement in advanced stages of the disease. In these cases high levels of prostate-specific antigen can be found in the cerebrospinal fluid. This comprehensive review presents the recent findings from the literature. © 2009 Springer Science+Business Media B.V.

PubMed | St Savvas Anticancer Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

15085 Background: Bevacizumab (BEV), a recombinant humanized monoclonal antibody against VEGF, is approved for intravenous administration in combination with standard chemotherapy (CT) regimens for advanced colorectal cancer (CRC); few data exist regarding the efficacy of BEV administered together with capecitabine (CAP) and irinotecan (IRI) (XELIRI). This study was conducted to investigate the safety and efficacy profile of the BEV/XELIRI regimen.Adult patients 18 years or older with advanced colorectal cancer, ECOG PS 2, exposed to 1 chemotherapy (CT) regimen not including IRI or CAP, had to receive BEV 7.5 mg/kg and IRI 220 mg/mThirty four patients were treated, the majority (29/85.3%) in first line; eighteen (53%) male, 16 (47%) female, aged 37-83 (median 69.5 years). Treatment was moderately tolerated with mainly gastrointestinal complications; haematological, cardiovascular and other toxicities were also recorded, but they were manageable. Overall RR was 47.1%, while 41.2% of patients achieved stable disease. Median PFS and OS were 8 (95% CI, 6.3 - 9.7) and 14 (95% CI, 11.5- 16.5) months, respectively with 16% progression-free and 62% alive at 12 months.The combination of BEV with XELIRI is a novel regimen with interesting activity and acceptable tolerability in advanced CRC, desserving further investigation by larger prospective studies comparing it with other BEV-containing and/or other regimens. No significant financial relationships to disclose.

PubMed | St Savvas Anticancer Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

10719 Background: Capecitabine and Vinorelbine have shown considerable activity given as single agent or in combination with other drugs. The aim of this single institution ph.II study is to evaluate the response to the combination of Capecitabine and Vinorelbine given as second line treatment in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines.The regimen consists of Capecitabine 2000 mg/m30 pts have been enrolled so far; according to statistical planning the total number of accrued pts should reach 63. Median age 55 yrs (30-76), median ECOG PS 1 (0-2), pre/postmenopausal 6/24. Number of metastatic sites: 1 in 6 pts, 2 in 15 pts, 3 in 6 pts and 4 in 3 pts. A total of 146 cycles was administered. Overall response rate 50% with CR in 2 (6.7%) pts, PR in 13 (43.3%) pts. Stable disease was observed in 4 (13.3%) pts, 8 (26.6%) pts had progressive disease and 3 (10%) were non evaluable.anemia gr 2 in 2 (6.7%) pts and gr 3 in 1 (3.3%) ptn, thrombocytopenia gr2 in 2 (6.7%) pts, granulocytopenia gr 2/3 in 17 (56.7%) pts and gr4 in 1 (3.3%) ptn. Gr 1/2 nausea or vomiting was observed in 5 (16.6%) pts and gr 3/4 in 2 (6.7%) pts. Vinorelbine induced phlebitis in 3 (10%) pts, gr1/2 diarrhea in 3 (10%) and fungal infection of the nail beds in 2 (6.7%) pts.Preleminary results suggest that the Capecitabine and Vinorelbine combination is an active and safe regimen for second line metastatic breast cancer treatment. The study remains open to achieve the planned patient accrual. No significant financial relationships to disclose.

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