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Volum 10 Numarul 3, 2004

138 EDITORIAL

139 Predictive Assays in Radiotherapy

O. Coza

U.M.Ph „Iuliu Haţieganu” Cluj-Napoca, Cancer Institute „I. Chiricuţǎ“ Cluj-Napoca

Predictive assays differs from the classical prognostic factors: a prognostic assay gives information on the likely outcome after standard treatment, whereas a predictive assay will aditionally indicate how the patient could best be treated. Predictive assays can be divided in two large categories: predictive assays for normal tissue response to radiotherapy and predictive assays for tumoral response to radiotherapy. The classical predictive test for normal tissue response to radiotherapy is the survival fraction of cells after a radiation dose of 2 Gy (SF2) determined by a colony assay. Newer techniques try to estimate the intrinsic radiosensitivity as radiation-induced chromosome aberrations, screenning potential radiation patients for mutations in genes involved in response to radiation or with the microarray DNA technique. The predictive assays for tumors can be included in three categories: intrinsic cellular radiosensitivity, oxygen status and proliferative potential. Alternatives to the clonogenic cell survival in order to estimate the intrinsic cellular radiosensitivity are: growth in soft agar, colorimetric assays and cell adhesive matix assay. The direct evaluation of tumor hypoxia is performed with the Eppendorf histograph, whereas indirect evaluation of the tumor oxygen status rely on the evaluation of tumor vascularization, tumor metabolic activity, detectind radiation hypoxic cells with the commet assay or the measure of hypoxic markers. The most studied method to estimate the proliferative potential of tumor cells is the potential dubling time (Tpot) and the labeling index (LI). Alternative assays evaluate the endogenous proliferation markers such as Ki67, PCNA, cyclins. In conclusion we can say that predictive assays are in developmental stage. In the future the field of array technology can be expected to play a significant role.

Key words: Predictive assay, Radiosensitivity, Oxygen status, Proliferative potential.

Radioterapie & Oncologie Medicalǎ, 2004, 3:139-148

149 Fibronectin – a Multifunctional Extracellular Matrix Glycoprotein. The Role in Invasion AND Metastasis

Ioana Berindan-Neagoe1, O.Bǎlǎcescu1, Rodica Rişcã2, Raluca Budiu1

1 Cancer Institute „I.Chiricuţǎ” Cluj-Napoca;
2 „BIONA“ Research and Development Center for Biotechnology

Breast cancer is usually characterized by an increase in connective tissue fibroblastic cells and extracellular matrix, the nature and molecular composition of which is gradually being revealed. One of the most studied components of extracellular matrix is fibronectin. It is called adhesive or structural glycoprotein, because it is part of the stabilizing scaffold, which links connective tissue cells to each other. Fibronectin molecules meets a variety of specific binding sites, which allow to participate actively in basic dynamic processes such as cell modulation, -attachment, -spreading and -migration. The immu­nohistochemical studies of fibronectin, on which this paper is based, were undertaken in order to investigate if changes of this protein between benign and malignant breast tissue would reflect the net effect of the different inherent characteristics of breast cancer cells known from experimental studies. A significant increase in stromal fibronectin was a consistent finding in all invasive carcinomas, permitting the discrimination between such tumors and benign proliferative lesions . A concurrent increase in the tumor cell expression of FN was found in poorly differentiated tumors, which could either be due to increased fibronectin production.

Key words: Breast cancer, Extracellular Matrix, Fibronectin, Adhesion, Invasion-metastasis.

Radioterapie & Oncologie Medicalǎ, 2004, 3:149-154

155 Microarray Applications in Oncology: Malignant Melanoma Stage I and II

O.Bǎlǎcescu1, Ioana Berindan-Neagoe1, Raluca Budiu1, V.Lazǎr2

1 Cancer Institute „I.Chiricuţǎ” Cluj-Napoca,

2 Gustave Roussy Institute, Villejuif, France

Microarray technology is a powerful molecular tool that allows the simultaneous study of the expression of thousands of genes or their RNA products, giving an accurate picture of gene expression in the cell at the time of the study. The applicability of this technnology in cancer field represents a real progress which could concur to understand the molecu­lar mechanisms involved in evolution and prognosis of cancer. Malignant melanoma represents an ideal frame for the study of molecular mechanisms involved in all the stepwise progression from melanocytes to aggressive metastatic melanoma.

Key words: Microarray, Melamoma.

Radioterapie & Oncologie Medicalǎ, 2004, 3:155-160

161 CER 1 on 3p21.3 and ovarian carcinoma Part I

Luminiţa Leluţiu1,2, C.D.Olinici1,2, S.Imreh3

1Dept. of Pathology, UMPh „Iuliu Haţieganu” Cluj-Napoca,

2Cancer Institute „I.Chiricuþã” Cluj-Napoca,

3Karolinska Institute, Microbiology and Tumor Biology Center, Stockholm, Sweden

The inability to detect the tumor at an early, curable stage and the lack of effective therapies for advanced disease may be solved by better understanding of the early genetic events and the progression mechanisms of this disease. Fluorescence in situ hybridization (FISH) is a technique often used for chromosome aberration detection and for identification of breakpoint, deletion and amplification regions in tumor cells. In this method a specific DNA sequence on the chromosome is visualized by hybridization with a fluorescent probe. Common eliminated region 1 (CER1) on 3p21.3 was found deleted in SCID mice tumors derived from normal chromosome 3 / tumor cell hybrids (elimination test). This region was eliminated both in human chromosome 3 / mouse fibrosarcoma and human chromosome 3 / human renal cell carcinoma hybrids. This transgression over tissues and species borders may indicate an important role of CER1 in tumor development from multiple tissues. The aim of this study was to investigate CER1 involvement in ovarian cancer.

Key words: Chromosome 3, Elimination test, CER1, FISH, PACs probes, Ovarian cancer.

Radioterapie & Oncologie Medicalǎ, 2004, 3:161-168

169 Surgical Treatment of Limbs Bone Metastasis

V.Turdean1, Maria Retegan Turdean2, O. Oţel1

1 Ortopaedic Dept., University District Hospital, Cluj-Napoca,

2 Medical Oncology Dept., University District Hospital, Cluj-Napoca

The skeleton is a common location of bone metastasis. The femur and humerus are the most frequent affected among the limbs bones. The surgical treatment is only a palliative one. Its aim is to improve the life quality, by preserving the walking ability, the general mobility, making easier the patient care. Surgery can be done in „prophylactic” way (to prevent a fracture of a bone containing a metastasis) or in „curative” way (to „cure” a fracture of a bone containing a metastasis). This study presents the results in the surgical treatment of bone metastasis located on the limbs bones on a series of 45 patients. The different surgical techniques used are discussed. According to this study ,the treatment of bone metastatic lesions is a multidisciplinary one, the surgery being ethically motivated, clinically indicated and cost effective. The prophylactic treatment, that means an early indication, is preferable.

Key words: Bone metastasis, Surgical treatment.

Radioterapie & Oncologie Medicalǎ, 2004, 3:169-179

180 Cardiac Performance in Pacients with Malignant Tumors Treated with Epirubicin

D. Rǎdulescu1, C. Duncea1, T. E. Ciuleanu2

1 Municipal University Hospital, 5th Medical Clinic Cluj-Napoca,

2Cancer Institute „I. Chiricuţǎ”, Cluj-Napoca

In the present study the left ventricular diastolic and systolic functions ware evaluated in patients treated with lower doses of epirubicin, by using Doppler echocardiography. 34 patients with different malignant tumors treated with doses of epirubicin of 450 mg/m2), and a gender and age matched group of 29 patients diagnosed with tumors who did not started treatment yet, were assessed by echocardiography. Left ventricular diastolic function was assessed by measuring the Doppler transmitral flow. We measured the maximal velocity of the E wave (rapid filling) and A wave (atrial filling). The ratio of Emax/Amax, the PHT of the E wave and the isovolumic relaxation time (IVRT) were also calculated. The left ventricular systolic performance was appreciated by measuring the global ejection fraction (EF). The left ventricular diastolic performance was altered in the treated group. In the treated group we noticed a significant decrease (p< 0.001) of E max (49.35% +/- 4.44 cm.sec compared with 69.45 +/- 11.99 in controls). A wave was significantly increased in the treated group compared to the control group (55.82 +/- 5.87 compared to 37.79+- 9.48; p< 0.001). The mitral E/ A ratio was subunitary in the treated group. The E wave pressure half time was prolonged in the epirubicin treated group, in comparison to the controls (64.76+/- 12.66 msec. compared to 52.89 +/-13.67; p < 0.001). The isovolumic relaxation time was prolonged in the treated group, in comparison to the controls (95.23 +/- 13.41 msec. compared to 86.79 +/-14.27; p < 0.05). The left ventricular systolic performance was not significantly altered in the treated group compared to the control group. Although the ejection fraction was lower in the treated group the difference did not reach statistical significance (59.45% +/- 7.14 compared to 60.17% +/- 7.59)

Key words: Anthracyclines, Doppler echocardiography, Left ventricular diastolic performance

Radioterapie & Oncologie Medicalǎ, 2004, 3:180-184

185 Cervical Thymic Cyst: Case Report and Review of the Literature

Magda Petrescu1, C.D. Olinici2, Doiniţa Crişan2

1Dept. of Pathology, Cluj County Clinical Hospital, Dept. of Pathology,

2UMPh „Iuliu Haţieganu” Cluj-Napoca

The authors report a case of a 13-year-old girl who showed a multilocular cervical thymic cyst. The clinical and pathologi­cal features as well the pathogenesis and the differential diagnosis of the entity are briefly discussed.

Key words: Cervical thymic cyst, Histology, Pathogenesis, Clinical features.

Radioterapie & Oncologie Medicalǎ, 2004, 3:185-188

189 European Chart of Patients Rights

192 Curriculum for the Specialist Training of Medical Practitioners in Radiotherapy (Radiation Oncology) within Europe recommended by ESTRO

Viorica Nagy

UMPhIuliu Haţieganu”, Cancer Insitute „Ion Chiricuţǎ”, Cluj-Napoca

The Curriculum for the Theoretical Education in Radiation Oncology in Europe from 1991 was updated under considera­tion of new developments in medicine in general, and in radiotherapy in particular. The updated European Core Curriculum for radiotherapists was endorsed by representatives of 35 European nations during the Brussels consensus conference on December 14, 2002. The updated document contains recommandations not only for the 5 year training curriculum but also for organisatoric and infrastructural aspects of teaching departments. A working party appointed by the European Board of radiotherapy developed the European logbook for trainees in radiotherapy, which is a robust instrument that allows the systematic collection of the information that needs to be recorded to monitor the professional development of European Trainees in Radiation Oncology.

Key words: Radiotherapy, Radiation oncology, Curriculum, Specialist training, Training logbook

Radioterapie & Oncologie Medicalǎ, 2004, 3:192-196

197 REVIEW OF LITERATURE

200 GUIDELINES FOR AUTHORS

201 The XIVth Congress of Romanian Society of Radiation Therapy and Medical Oncology, September 23-25, 2004, Arad, Romania. Abstracts