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Volum 14 Numarul 3, 2008

137 EDITORIAL

Gabriel Kacsó

138 Key Signaling Pathways in Apoptosis

Claudia Burz1, Ioana Berindan Neagoe1,2, Eleonora Dronca2, Rareş Buiga2

1Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Immunology Department;2Ion Chiricuta Cancer Center Cluj-Napoca, Romania

Apoptosis, or programmed cell death, is a physiological process vital for the embryologic development and the maintenance of ho­meostasis in multicellular organisms. However, it is also involved in a wide range of pathological processes such as neurodegenera­tive and immunologic diseases, cancer and premature senescence. Classically there are two major pathways of apoptosis. One path­way is via death receptors on the cell surface, such as the tumour necrosis factor family (TNF R1) and the other is initiated by cyto­chrome C release from mitochondria. Recently, many publications suggest the implication of reactive oxygen species in normal cell proliferation, but also in cell apoptosis. Although many of the vital apoptotic proteins have been identified, the molecular pathways of these proteins still remain to be elucidated. This review provides reference concerning both the fundamental apoptotic molecules and their interactions and also the modulation pathways of apoptosis for prevention and treatment of different diseases.

Key words: Apoptosis, Diseases, Mitochondria, Target.

144 Present Trends in the Management of Locally Advanced Epithelial Ovarian Cancer

Viorica Magdalena Nagy

Ion Chiricuta Cancer Center Cluj-Napoca, Romania, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca

Epithelial ovarian cancer is the most lethal gynecologic malignancy. It is estimated that 75% of women with ovarian cancer present with stage III or IV disease. In the management of epithelial ovarian cancer , surgery plays three roles. It allows the definitive histo­logical diagnosis to be made; it allows for adequate staging and assessment of the extent of disease; and it allows for optimal cytore­duction, or debulking, a critical component to successful treatment. Based on the results of trials showing the efficacy and favorable toxicity profile on platinum agents (especially carboplatin) plus the survival advantages associated with paclitaxel therapy (GOG study 111 and OV-10), in the present, the standard of care for first-line chemotherapy is a regimen using a platinum/taxane combina­tion. The majority of patients with advanced epithelial ovarian cancer relapse after first-line treatment despite the fact that the vast majority achieve an initial remission. There are two major strategies for improving the outcome of patients with advanced disease. The first is better initial therapy with new agents, and the second is using currently available drugs or novel compounds to maintain or consolidate the remissions obtained with standard initial treatment.

Key words: Epithelial ovarian cancer, Cytoreductive surgery, Primary chemotherapy, Consolidation therapy, Maintenance therapy.

151 Chemotherapy Results in Testicular Germ Cell Tumors – Updates and Controversies

Cristina Ligia Cebotaru

Ion Chiricuta Cancer Center Cluj-Napoca, Department. of Radiotherapy I, Romania

Testicular cancer is an example of what can be learned from well conducted clinical trials. The current standard chemotherapy in Germ Cell Tumors is based on a long series of randomized controlled clinical trials, despite the fact that this is a relatively rare tu­mor. More than 90% of patients are now cured, even in advanced stages and the treatment of Germ Cell Tumors represents one of the great successes of medical science. All attempts should be made to cure patients and to limit toxicity. This article reviewed all stan­dards of care with the current controversies and updates communicated or published at the latest congresses.

Key words: Germ Cell Tumor, Chemotherapy, Radiotherapy, Surgery.

158 Clinical Management of Early Menopause in Young Women with Breast Cancer

Dorina Larisa Ciule

Emergency County Hospital, Cluj, Department of Oncology, Cluj-Napoca

Early menopause is the consequence of systemic treatment for premenopausal breast cancer. The diagnosis and treatment of breast cancer can result in physical and psychological changes, that are associated with early and long-term adverse effects. The most com­mon symptoms experienced are hot flushes and decreased sexual function. Therapeutic options for hot flushes include serotoninergic antidepressants and gabapentin, wich provides a 50-65% reduction in hot flush frequency, or stress management. Providing advice and treating vaginal dryness and sexual counseling can alleviate sexual dysfunction. However, the options for fertility preservation are limited by the individual risk of the patient. Late effects caused by estrogen deficiency are cognitive dysfunction, cardiovascular disease, bone loss, and overweight, for wich specific treatment and counseling is needed to provide an acceptable quality of life.

Key words: Breast cancer, Young women, Premature menopause, Quality of life.

163 Pancreatic Neuroendocrine Tumors – Diagnostic and Therapeutic Opportunities in a General Surgery Department

Mircea Cazacu1, Nicolae Rednic2, Doru Munteanu3, Flaviu Mureşan1, Iacob Domşa4 , Răzvan Simescu1, Gabriel Petre1, Alexandrina Mureşan5

University Hospital: 1,4 Surgery Clinic Cluj-Napoca; 2,4 Medical Clinic; 3Radiology Department; 4Pathology Department; 5Intensive Care Unit

Objective: analysis of the diagnostic and treatment chances in a regularly equipped General Surgery department for patients diag-nosed with pancreatic neuroendocrine tumors (PNET). Method: retrospective study of the clinical data. Patients: all patients who underwent surgery for PNET over an 8 year period (2000-2007). Results: 10 patients with a median age of 51.9 years (range between 21-71 years) were diagnosed with functional PNET in 6/10 cases, and non-functional PNET in 4/10 cases. The diagnosis was estab-lished using clinical examination, biochemical data analysis, standard ultrasonography (US) and computed tomography (CT). All pa-tients had pathological confirmation by haematoxyline-eosin staining (HE), histochemical (HC) or immunhistochemical (IHC) analy-sis of the tumor – 8 cases, or of the biopsy sample – 2 cases. 9 patients had a benign tumor, one patient a malignant one. US and CT were able to identify the pancreatic tumor in all the cases. US was positive in 8/10 patients and CT in 4/9 patients. Surgical treatment was partial pancreatic resection- 4 cases, tumor enucleation – 4 cases. In 2 cases biopsy sampling was performed. Morbidity – 3/10 cases due to pancreatic fistula. Mortality – 1/10 cases due to cardio-vascular complications. Conclusions: diagnosis of PNET can be established using standard imaging methods: US and/or CT-scan. These patients can be treated by classical surgery – pancreatic re-section or tumor enucleation. Morbidity is acceptable and mortality is usually caused by associated conditions.

Key words: Pancreatic neuroendocrine tumors, Clinical diagnosis, US, CT, Pancreatic resection, Tumor enucleation.

167 Photodynamic Effect of a Water Soluble Porphyrin Evaluated on Two Cancer Cell Lines

Maria Perde-Schrepler1, Piroska Virág1, Eva Fischer-Fodor1, Ioana Brie1 ,
Corina Tatomir1, Olga Şoriţău1, Ion Dan Postescu1, Gabriela Cherecheş1 ,
Valentin Cernea1,3, Simina Dreve2

1 Ion Chiricuta Cancer Center, Cluj-Napoca, Romania; 2 National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania; 3 Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

Purpose: The aim of our study was to test in vitro the potential use of a newly synthesized porphyrin as a photosensitizer in photodynamic therapy, as a first step for its application in the treatment of malignant tumors. Materials and methods: Two cancer cell lines: HeLa (cervix carcinoma) and WM35 (primary melanoma) were used. Visible light of 615-630nm wavelength was delivered using a LED system (5mW/cm2 intensity at the surface of the cells). Intracellular localization of the sensitizer was visualized by fluorescence microscopy, while cell survival after photodynamic treatment was assessed by MTT test. Results: Partial colocalization of TSPP fluorescence with the mitho­condrial dye (Rhodamine 123) suggests mithocondrial localization of the porphyrin leading to cell death probably by apoptosis. Irradiation alone did not decrease cell survival. TSPP without light exposure was cytotoxic only at high concentrations (IC50= 1428 µg/ml for HeLa and 701 µg/ml for WM35 cells). In both cell lines, after light exposure, photodynamic effect was obtained, cell survival decreasing propor­tionally with TSPP concentration and energy densities of light. HeLa showed a statistically significant (p<0,0005) higher sensitivity for PDT. Conclusions: TSPP proved to be a potent and effective photosensitiser in vitro for both tumor cell lines tested.

Key words: Photodynamic therapy, In vitro, Porphyrin, Phototoxicity.

172 Three-Dimensional Conformal-Radiotherapy inCombined-Modality Treatment for advanced Non-small cell lung cancer –A Clinical Case Presentation

Petronela Rusu1, Nicolae Ghilezan1,2

1Ion Chiricuta Cancer Center Cluj-Napoca; 2 Iuliu Hatieganu University of Medicine and Farmacy, Cluj-Napoca, Romania

The clinical case of one of the first patients from the so-called “learning period” of integration of three-dimensional conformal radio-therapy (3D-CRT) in the combined treatment for patients with locally advanced inoperable stage III Non-small cell lung cancer is presented. Our experience in every step of optimization of 3D-CRT beginning with target volumes and organs at risk definition and delineation, treatment design and beam arrangements, dose prescription, dose distribution and dose/volume histogram analysis, set-up verification, evaluation of response to treatment and acute and late toxicities, incorporated in a combined strategy with concurrent chemotherapy, preceded by induction chemotherapy and followed by consolidation chemotherapy is also evaluated.

Key words: Three-dimensional conformal radiotherapy, Combined chemoradiotherapy, Locally advanced NSCLC.

182 Primary Neuroendocrine Carcinoma of the Uterine Cervix. Report of TwoCases and Review of the Literature

Ciprian Chira1, Viorica Magdalena Nagy1,6, Ovidiu Coza2,6, Alin Rancea1,6, Octavian Chiş3, Cristina Cebotaru4, Rareş Buiga5, Mihaela Galatâr5

Ion Chiricuţă Cancer Center, Cluj-Napoca: 1Dept. of Radiation Oncology, 2Dept. of Surgical On
cology,
3Dept. of Otolaryngology, 4Dept. of Medical Oncology, 5Dept. of Pathology; 6IuliuHaţieganuUni-versityof Medicine and Pharmacy Cluj-Napoca

In this paper we report two cases of neuroendocrine carcinoma of the cervix uteri that developed in two women, a 45 year-old and a 72 year-old respectively. In both cases the tumor was diagnosed in advanced stages and radiation therapy was performed first, fol­lowed by radical abdominal hysterectomy and pelvic lymphadenectomy. Later both patients presented with distant metastatic spread and although further treatment was given one patient died at 10 months from presentation, shortly after metastatic brain surgery. The second patient had persistent disease after surgery, radiation therapy and chemotherapy following a left laterocervical dissemination. This report discusses the clinipathological features, behaviour and treatment, of these aggressive tumors, as well as insights from lit­erature, with emphasis on small cell neuroendocrine carcinomas.

Key words: Neuroendocrine tumor, Small cell carcinoma, Cervical cancer, Case presentations.

190 Guidance for Authors on the Preparation and Submission of Manuscripts to the Journal of Radiotherapy and Medical Oncology