Journal of B.U.ON.: official journal of the Balkan Union of Oncology (J BUON)

Publications in this journal

• Article: THE CORRELATION OF SERUM PROTEOMICS PATTERNS OF SCD200, STRAIL, VITAMINE-D AND HOMOCYSTEIN WITH QUANTITATIVE FDG-PET/CT FINDINGS IN NEWLY DIAGNOSED NON-SMALL CELL LUNG CANCER

  Arzu Didem Yalcin, Saadet Gumuslu, Bulent Kargi, Aysegul Kargi, Burhan Savas, Antonia Dimitrakopoulou-Strauss, Ludwig G. Strauss
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 03/2013;
• Article: The role of VEGF and other parameters in tracking the clinical course in metronomic chemotherapy.

  Deniz Ekici, Aysegul Kargi, Didem Yalcin A, Burhan Savas
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  ABSTRACT: Purpose: The purpose of this study was to investigate the effect of metronomic chemotherapy on serum vascular endothelial growth factor (VEGF) levels in cancer patients. Methods: The study included 11 metastatic cancer patients who received daily 50 mg cyclophosphamide and biweekly 5 mg methotrexate per os as metronomic chemotherapy. Bevacizumab together with FOLFIRI chemotherapy was administered as anti-angiogenic treatment in another group of 16 metastatic colorectal carcinoma patients. Furthermore, VEGF levels of 10 healthy individuals and 5 cord blood samples served for comparisons. VEGF levels of patients before therapy and 3 months after treatment were analyzed and compared. Results: Serum VEGF levels prior to metronomic chemotherapy were higher compared with the healthy controls (p=0.0001). Similarly, serum VEGF levels prior to the bevacizumab-based chemoimmunotherapy were significantly higher compared with the healthy controls (p=0.005). In patients on metronomic chemotherapy VEGF levels showed non significant decrease (p=0.075). On the contary, VEGF levels decreased significantly (p=0.002) with bevacizumab treatment. Conclusion: Serum VEGF levels may be used for assessing of the efficacy of anti-angiogenic therapies.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2013; 1(18):245-252.
• Article: THE ROLE OF “VEGF” AND OTHER PARAMETERS IN TRACKING THE CLINICAL COURSE IN METRONOMIC THERAPY

  Deniz Ekici, Aysegul Kargi, Arzu Didem Yalcin, Burhan Savas
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2013; 18.
• Article: mir-17 in Imatinib Resistance and Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia Cells.

  Firatligil B, Avci CB, Baran Y
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  ABSTRACT: Purpose. miRNAs are small, non-protein coding RNA molecules having crucial roles in gene ragulation. Abnormal expression of miRNAs has vital effects in the pathogenesis of human cancers especially in leukemia. Regarding to their importance in pathology of cancers, miRNAs have become crucial targets for the diagnosis, classification and even treatment of various human cancers. mir-17 miRNA has oncogenic activity through downregulation of CDKN1A, p21 and E2F1 tumor suppressor genes. In this study, we examined expression levels miR-17 in imatinib-sensitive and resistant CML cells. On the other hand, we also determined expression levels of mir-17 in response to tyrosine kinase inhibitors imatinib, nilotinib and dasatinib used for the treatment of CML. Methods. The expression profiles of mir-17 was analysed by Stem-Loop RT-PCR. Results. The results revealed that there were significant increases in expression levels of mir-17 in sensitive and imatinib resistant cells as compared peripheral blood mononuclear cells. On the other hand, significant decreases were observed in mir-17 levels in response to imatinib, nilotinib and dasatinib. Conclusion. These results may show that mir-17 can be used for diagnosis and treatment of chronic myeloid leukemia.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2013; 18(2).
• Article: THE ROLE OF SERUM VEGF LEVELS TRACKING THE CLINICAL COURSE IN ANTI-ANGIOGENIC AND METRONOMIC CHEMOTHERAPY

  Deniz Ekici, Aysegul Kargi, Arzu Didem Yalcin, Burhan Savas
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 12/2012;
• Article: Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients.

  A O Kaya, N Gunel, M Benekli, N Akyurek, S Buyukberber, H Tatli, U Coskun, R Yildiz, E Yaman, B Ozturk
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  ABSTRACT: Purpose: Hypoxia is common in many solid tumors such as breast, head-neck, and soft tissue malignancies. Hypoxia causes overexpression of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA IX) which are associated with unfavorable prognosis in breast cancer. In our study, we evaluated HIF-1α and CA IX expression in patients with breast cancer. Methods: Between June 1996 and June 2008, 111 women with breast cancer were evaluated. Estrogen receptor (ER) and progesterone receptor (PR) status and Her2/ neu expression were evaluated by immunohistochemical methods. Her-2/neu expression was also assessed by FISH method when needed. Two groups were created: ER and PR positive, Her-2/neu negative (group 1, n=56); and ER and PR negative, Her-2/neu positive (group 2, n=55). HIF-1α and CA IX expressions were investigated in both groups and results were compared. In addition, we investigated the association between HIF-1α and CA IX expressions with stage, grade, lymph node metastasis, tumor size, menopause status and survival. Results: Median patient age in group 1 was 52 years (range 34-77), and in group 2 47 years (range 27-83). HIF-1α expression was detected in 26 (46.4%) of group 1 and in 46 (83.6%) of group 2 patients (p=0.0001). CA IX expression was detected in 25 (46.4%) of group 1 and in 37 (67.3%) of group 2 patients (p7equals;0.0137rpar;. In group 1, median disease free survival (DFS) was 97 months and in group 2 46 months (p=0.0308). In group 1, median overall survival (OS) was 108 months and in group 2 75 months (p=0.0339). Conclusion: HIF-1α and CA IX overexpressions are observed more often in ER and PR negative, Her-2/neu positive breast cancer and are associated with poor survival.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):663-668.
• Article: Current approach to epithelial ovarian cancer based on the concept of cancer stem cells.

  B Djordjevic, S Stojanovic, I Conic, L Jankovic-Velickovic, P Vukomanovic, R Zivadinovic, M Vukadinovic
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  ABSTRACT: Epithelial ovarian cancer (EOC) is the most common ovarian malignancy. EOCs comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, genetic alterations, and biological behaviors. Currently, there is no effective screening for early detection of EOCs and more than two-thirds of EOC patients are diagnosed with advanced stage disease. The major limiting factors in the treatment of EOC patients are recurrence and chemoresistance. Recent studies suggest that EOCs, like other solid tumors, contain distinct populations of cells that are responsible for tumor initiation, maintenance and growth. These cells, termed cancer stem cells (CSCs), display some of the features of normal stem cells and are thought to evade current chemotherapeutic strategies for the treatment of EOCs. Distinguishing CSC-associated antigen profiles may elucidate novel, more sensitive biomarkers for early detection of EOCs and provide molecular targets for the development of new treatment modalities. This review summarizes the current approaches to EOCs based on the concept of CSCs and evaluates their clinical relevance.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):627-636.
• Article: Cancer stem cells in oncology.

  I Cetin, M Topcul
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  ABSTRACT: Cancer stem cells (CSCs) possess several characteristics including self-renewal, pluripotency and tumorigenicity and constitute a rare population in a tumor mass. Because conventional cancer therapies can not kill CSCs, these cells are responsible for tumor relapse and metastasis. Currently, with advances in the identification of CSCs, the importance of these cells is increasing in the field of cancer diagnosis and prognosis. In addition, clarifying the mechanisms responsible for the maintenance of CSCs properties led to the development of CSC-targeted therapies.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):644-648.
• Article: Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer.

  E Akun, K Okutur, S Seber, T Korkmaz, K Aydin, M Bozkurt, E Namal, B Hasbal, C Tecimer, G Demir
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  ABSTRACT: Purpose: To determine the clinical features of bevacizumab-associated toxicities in metastatic colorectal cancer (MCRC) patients. Methods: The medical records of 60 patients with MCRC who were treated with chemotherapy including bevacizumab in the first-line setting were retrospectively evaluated. Results: Bevacizumab was administered along with irinotecan plus 5-fluorouracil7sol;leucovorin (5-FU/LV) to 44 patients, 57horbar;FU7sol;LV+oxaliplatin to 8 patients, capecitabine+oxaliplatin to 6 patients and 5-FU/LV to 2 patients. The total number of the cycles received was 381 (median 6, range 17horbar;13). The most common bevacizumab-related toxicity was grade 1-2 bleeding (28%) followed by hypertension (17%). Grade 1-2 proteinuria was seen in 8% of the patients (no grade 3-4 proteinuria). Arterial thromboembolic events (ATE) were not observed, however 3 patients (5%) had experienced grade 3-4 venous thromboembolic events. In 3 patients (5%) grade 1-2 wound complications were seen (delayed wound healing in the place of the venous access device in 2, and wound infection in 1). In addition, gastrointestinal perforation (GIP) was seen in 3 (5%) patients. Two of the patients were treated by surgical intervention and one patient died of sepsis. Conclusion: Bevacizumab is well tolerated when combined with various chemotherapy regimens. As bevacizumab is becoming widely used in the routine oncology practice, further studies which investigate the mechanism of bevacizumab-associated toxicities are warranted to develop effective management strategies for these adverse events.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):669-676.
• Article: Transforming growth factor β repressor, SnoN, is overexpressed in human gastrointestinal stromal tumors.

  V Bravou, P Papanastasopoulos, D Verras, I Kotsikogianni, V Damaskou, M Repanti
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  ABSTRACT: Purpose: The transforming growth factor bgr; (TGF-β)/ Smad pathway is implicated in the development of interstitial cells of Cajal. The aim of this study was to examine the role of this pathway in human gastrointestinal stromal tumors (GISTs). Methods: The expression of TGF-β receptor II (TβRII), phosphorylated Smad2 (p-Smad2), SnoN, p21(WAF17sol;CIP1) and p27(KIP1) was examined by immunohistochemistry in 30 hu-man GISTs in relation to prognostic factors. Results: TβRII was expressed in 76.9% of the cases. All cases were positive for p-Smad2 and SnoN, with significantly higher expression levels in small intestinal compared to gastric GISTs. Downregulation of p21(WAF1/CIP1) and p27(KIP1) was found in 78.6% and 46.4% of the cases respectively, while cytoplasmic expression of p27(KIP1) was also noted in 50% of GISTs. Conclusions: TGF-β/Smad pathway may contribute to GIST pathogenesis. SnoN overexpression and low levels of p21(WAF1)/CIP1 and p27(KIP1) may be of importance in GISTs.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):684-690.
• Article: Expression of pSTAT3 in human colorectal carcinoma: correlation with clinico-pathological parameters.

  A Zizi-Sermpetzoglou, V Savvaidou, D Myoteri, S Rizos, A Marinis
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  ABSTRACT: Purpose: Signal transducers and activators of transcription (STATs) are tyrosine phosphorylated transcription factors activated by the Jak family kinases. Various ligands, including interferons and growth factors induce activation of STATs. STATs are key signaling molecules in malignant transformation and tumor progression. Constitutive activation of the STAT3 has been observed in a wide variety of human malignancies. The purpose of this study was to evaluate the clinical significance of phosphorylated (p) STAT3 expression in human colorectal adenocarcinomas (CRC). Methods: 135 primary human CRC were immunohistochemically studied, from which 11 were intramucosal and 124 invasive carcinomas. The observed pattern of pSTAT3 immunostaining was nuclear and cytoplasmic. Nuclear pSTAT3 staining was calculated as the number of pSTAT3 positive nuclei divided by the total number of nuclei in at least 10 fields, and then expressed as a percentage. Cytoplasmic positivity of pSTAT3 was measured, depending on the intensity of immunoreactivity and scored as mild, moderate and intense. Results: Positive staining for pSTAT3 immunoreactivity was significantly correlated with the depth of tumor invasion (p<0.001), venous invasion (p<0.05), lymph node metastasis (p<0.05) and advanced Dukes stage (p<0.001). There was no significant correlation between pSTAT3 immunoreactivity and poor differentiation of CRC. Conclusion: The expression of pSTAT3 is an important factor related to tumor and vascular invasion, nodal involvement and advanced CRC stage.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):691-694.
• Article: PTEN expression in non small cell lung carcinoma based on digitized image analysis.

  I Panagiotou, E Tsiambas, A C Lazaris, N Kavantzas, M Konstantinou, P Kalkandi, V Ragkos, G E Metaxas, D K Roukas, G Vilaras, E Patsouris
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  ABSTRACT: Purpose: HER2 depended signalling pathway is dereg-ulated in a subset of non small cell lung carcinoma (NSCLC). The tumor suppressor gene PTEN (10q21) regulates the HER2/PI3K/Akt signalling pathway. Our aim was to evaluate PTEN protein expression in NSCLC based on a quantitative analysis method correlating also the results with clinicopathological parameters. Methods: Protein expression was determined by immunohistochemistry (IHC) in 61 paraffin-embedded cases of patients with NSCLC. Digital image analysis (staining intensity levels) was performed in the corresponding immunostained slides. Results: Loss of PTEN expression was observed in 24 (39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%) cases. Multivariate analysis determined that PTEN overexpression was associated with lower risk to develop metastases (p=0.05). Conclusion: PTEN deregulation is a relatively frequent genetic event in NSCLC, associated with progressive metastatic process in those patients. Because of binding to the ErbB2 receptor, trastuzumab stabilizes and activates PTEN gene, and loss of its expression negatively affects the response rates in such patients.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):719-723.
• Article: It is not only the empty vials that go into the garbage can during chemotherapy drugs preparation: A cost analysis of unused chemotherapy drugs in cancer treatment.

  A Ata, H Abali, E Yengel, A Arican
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  ABSTRACT: Purpose: Cancer therapy is a costly treatment. Costs of drugs used in cancer therapy are gradually increasing with the addition of new and expensive drugs. This fact imposes obligation on reasonable drug usage. Occasionally, all of the prescribed drugs are not used for various reasons, and a number of drugs can be left over. In this study, we aimed to calculate the costs of unused chemotherapeutic drugs in our oncology clinics. Methods: A total of 117 patients with 17 different types of cancer were administered 32 cancer therapy protocols during 2 months. After administration of ideal doses of the prescribed drugs calculated on an individual basis, the number of unused drug doses in the packages was recorded and the costs of the unused drugs were calculated based on current prices of the drugs. Results: The cumulative cost of the unused drugs calculated for all patients was US dollars (USD) 6406.93, and average cost of the drug per capita was USD 54.76. Minimal and maximal unused drug costs per drug were USD 0.29 for 5-fluorouracil, and USD 247.12 for bevacizumab, respectively. Minimal increase in drug costs per recipe was USD 0.50 for a prescription containing cyclophosphamide and 5-fluorouracil, while the total cost of bevacizumab plus irinotecan combination increased tremendously to USD 309.12. Among chemotherapeutic protocols the cheapest one was AC (adriamycin, cyclophosphamide) with USD 4.77, while the most expensive one (USD 116.02) was FOLFIRI-B (5-fluorouracil, calcium folinate, irinotecan, and bevacizumab). Conclusion: The important financial burden of unused drugs goes unrecognized among routine chemotherapeutic applications. In order to be able to avoid this extravagance, drug industry, prescribing physicians, and practice nurses must assume important roles.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):781-784.
• Article: Long-term advanced cholangiocarcinoma survivor with single-agent capecitabine.

  I Petekkaya, G Gezgen, E C Roach, M Solak, I Gullu
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):796.
• Article: Is there a correlation between molecular markers and response to neoadjuvant chemoradiotherapy in locally advanced squamous cell esophageal cancer?

  T Arsenijevic, M Micev, V Nikolic, D Gavrilovic, S Radulovic, P Pesko
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  ABSTRACT: Purpose: To evaluate the expression of epidermal growth factor receptor (EGFR), p53, p21 and thymidylate synthase (TS) in a pretherapy biopsy specimen of locally advanced squamous cell esophageal cancer and correlate these markers with response to neoadjuvant chemoradiotherapy. Methods: Sixty-two patients with histopathologically proven locally advanced (T3 or greater) squamous cell esophageal cancer were enrolled. The expression of EGRF, p53, p21 and TS markers was assessed with immunohistochemistry. Semiquantitative assessment of expression of these markers was performed based on the percent of the stained cells. Radiotherapy (45-50.4 Gy) was delivered concomitantly with 5-fluorouracil (5-FU)/leucovorin (LV)/cisplatin (CIS) chemotherapy. Five to 6 weeks after chemoradiation, response to treatment was assessed. Medically fit and operable patients were operated. The resected material underwent histopathological evaluation of tumor expansion, histological classification after initial multimodality treatment (yp TNM), residual status and tumor regression grade (TRG). Results: Out of 62 patients enrolled, 41 (66%) were evaluated for molecular markers. Clinical response rate was 43.9%. Out of 41 patients, 12 (29%) underwent surgery. TRG 1 was noted in 58% of the patients. In a pretherapy tumor specimen, positive expression was noted in 80, 90, 80 and 71% for EGFR, p53, p21 and TS, respectively. We noted no statistically significant difference neither between tumor marker expression and clinical response to chemoradiation, nor between tumor marker expression and TRG. Conclusion: We registered no difference in response to treatment between EGFR, TS, p21 and p53 positive and negative staining.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):706-711.
• Article: Evaluation of apoptosis in classical Hodgkin's lymphoma comparing different methods.

  E C Georgiadi, N Sachinis, G Dimtsas, T P Vassilakopoulos, C Kittas, I A Doussis-Anagnostopoulou
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  ABSTRACT: Purpose: Apoptosis is a type of programmed cell death (PCD) with specific morphologic changes in the dying cell. Since classical Hodgkin's lymphoma (cHL) is characterised by abnormalities in the apoptotic pathways, apoptosis may play a central role in its pathogenesis. Our purpose was to estimate the apoptotic process in cases of cHL using 3 different, widely accepted methods, comparing their results as well as with those found in the literature. Methods: Detection of apoptosis was performed in 76 cases of cHL, using morphological criteria, TUNEL assay (TUNEL apoptotic index; T-AI) and immunohistochemical detection of active caspase 3 (casp3-AI) on paraffin embedded sections. Results: When both apoptotic (MA) and mummified (mummi-I) cells were evaluated by morphological apoptotic index (morph-AI), the median value was 10.3%, while for MA and mummi-I the results were 3.4% and 6%, respectively. T-AI and casp3-AI values were 10.9% and 1.9%, respectively. Morph-AI was significantly higher in the mixed cellularity (MC) subtype (p7equals;0.047rpar;, while MA was significantly higher in the male subgroup (p7equals;0.03). MA was strongly correlated with casp37horbar;AI (p=0.01). Conclusion: Detection of apoptosis has become an important parameter in understanding tumor pathology and in designing antitumor treatment. A combination of methods is proposed in order to estimate accurately this form of cell death.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):746-752.
• Article: Percutaneous radiofrequency ablation of small renal cell carcinoma: technique, complications, and outcomes.

  P Popovic, S Lukic, M Mijailovic, V Salapura, M Garbajs, K Surlan Popovic
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  ABSTRACT: Imaging-guided radiofrequency ablation (RFA) is an option for treatment in patients with early-stage small renal cell carcinomas (RCCs). RFA has been introduced to treat focal renal tumors, particularly incidental lesions <3 cm in elderly patients and those with comorbid conditions. Other uses have included treatment in patients with von Hippel-Lindau syndrome and other diseases that predispose patients to multiple renal carcinomas, where renal parenchymal preservation is desired. It appears that this technique has a low complication rate, preserves renal function, is well tolerated by the patients, and, in a high percentage of patients, can eradicate small renal tumors. Techniques, patient selection, complications, and results are discussed.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):621-626.
• Article: Surgical management of endometrial cancer. A critical review.

  E Halkia, N Kalinoglou, J Spiliotis
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  ABSTRACT: Endometrial cancer (EC) is a common gynecological malignancy. Prognosis depends on 3 main factors: histological subtype, depth of invasion into the myometrium and lymph node involvement. Surgery remains the gold standard of treatment for this cancer. The aim of this article was to review the surgical approach and the new techniques along with the clarification of some controversial aspects concerning the management of advanced disease stages and the role of lymph node dissection. Surgery of EC remains the treatment of choice in the management of early stage disease. The role of lymph node dissection remains controversial.
  Journal of B.U.ON.: official journal of the Balkan Union of Oncology 10/2012; 17(4):637-643.