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1 Breast Carcinoma-Associated Abstracts of the 8th International Conference of Anticancer Research, 17-22 October 2008, Kos, Greece 1 methods have been successfully employed in the clinical BREAST CARCINOMA-ASSOCIATED FIBROBLASTS treatment of diffuse (liquid) malignancies but have, as of yet, AND THEIR ADJACENT COUNTERPARTS DISPLAY failed to achieve similar successes in the setting of solid TUMOR-ASSOCIATED FEATURES tumors. This talk will provide an overview of the successes of targeted radionuclide therapy, outline some of the hurdles that Nahed M. Hawsawi, Hazem Ghebeh, Siti-Faujiah remain and discuss possible approaches that can be taken to Hendrayani, Asma Tulbah, Maha Al-Eid, Taher Al-Tweigeri, enhance therapeutic outcomes. Dahish Ajareem, Ayodele Alaiya, Said Dermime and Abdelilah Aboussekhra 3 King Faisal Specialist Hospital and Research Center, OPTIMIZING ANTIBODY-BASED MOLECULES Department of Biological and Medical Research, MBC # 03, FOR RADIOIMMUNOTHERAPY AND PO BOX 3354, Riyadh 11211, KSA RADIOIMMUNOIMAGING Gregory P. Adams It has become clear that the genesis and thrive of carcinomas depend not only on genetic and epigenetic alterations in Department of Medical Oncology, Fox Chase Cancer Center, epithelial cells, but also on changes in the stroma. In order to 333 Cottman Ave, Philadelphia, PA 19111, USA identify these changes, we have undertaken cellular and molecular characterization of carcinoma-associated fibroblasts Due to prolonged retention in the circulation and restricted (CAFs) and their adjacent counterparts (TCFs) isolated from ability to penetrate into solid tumors, intact antibodies are 12 breast cancer patients. Normal breast fibroblasts (NBF) often not the most effective vehicles for the delivery of from plastic surgery were used as normal control. While the α- radioisotopes to tumors for therapeutic and imaging SMA protein was undetectable in NBF cells, CAFs and TCFs applications. However, antibody-based molecules can be were both positive for this myofibroblast marker. Furthermore, rationally modified to improve their ability to selectively the p53/p21 response pathway to γ-rays was defective in 70% deliver radioisotopes to tumor tissue. This presentation will CAFs, whilst it was normal in all the TCF and NBF cells. In review our experience and that of others on the impact of addition, the basal levels of p53 and p21 tumor suppressor altering antibody size, affinity and ability to interact with FcRn proteins were lower in 83% of CAFs, and modulated in the on targeting efficiency. majority of TCFs, as compared to NBFs. Interestingly, both TCFs and CAFs expressed high levels of the cancer marker 4 survivin, and consequently exhibited high resistance to the CETUXIMAB WITH HEPATIC ARTERIAL INFUSION killing effects of cisplatin and UV light. Moreover, most CAFs OF CHEMOTHERAPY FOR THE TREATMENT OF were positive for the proliferation marker Ki-67 and exhibited COLORECTAL CANCER LIVER METASTASES high proliferation rate as compared to NBF and TCF cells. B. Neyns, M. Aerts, Y. Van Nieuwenhove, C. Fontaine, Using the 2 dimensional gel electrophoresis technique, we have L. De Coster, D. Schallier, J. Vanderauwera, F. De Munck, also shown that CAFs, TCFs and NBF present different F. Vandenbroucke, H. Everaert, V. Meert, J. De Mey, proteome profiles, with many proteins differentially expressed M. De Ridder, G. Delvaux and J. De Grève between these cells, indicating that different genetic alterations occur in breast carcinoma-associated fibroblasts and also their UZ-Brussel, Laarbeeklaan 101, 1090 Jette, Belgium corresponding adjacent counterparts. Background: Both hepatic arterial infusion (HAI) of 2 chemotherapy and cetuximab (CET) have interesting activity INTRODUCTION TO RADIONUCLIDE THERAPY for the treatment of colorectal cancer liver metastases (CRC- LM). Patients and Methods: Intravenous CET with HAI Gregory P. Adams1, Jorgen Carlsson2 and Torgny Stigbrand3 oxaliplatin (OXA) or i.v. Irinotecan (IRI) followed by HAI of 1Department of Medical Oncology, Fox Chase Cancer infusion of folic acid modulated 5-fluorouracil 5-FU/l-FA was Center, Philadelphia, BA, USA; administered to patients (pts) with CRC-LM who had failed 2Biomedical Radiation Sciences, Uppsala University, at least one line of prior chemotherapy. Results: Eight pts Sweden; received i.v. CET with HAI-OXA (5 pts) and i.v.-IRI (3 pts) 3Department of Immunology and Clinical Microbiology, and HAI-5-FU/l-FA. Adverse events: repeated grade 3 skin University of Umea, Sweden toxicity (1 pt), abdominal pain with elevated liver enzymes and asthenia (2 pts), duodenal ulcer (2 pts) with catheter Targeted radionuclide therapy can provide an effective method migration and intestinal bleeding (1 pt), reversible interstitial of selectively focusing cytotoxic effects on tumor cells. These pneumonitis (1 pt), and cystic bile duct dilatation (2 pts) with 3185 ANTICANCER RESEARCH 28: 3157-3556 (2008) arteriobiliary fistulisation (1 pt). A partial response was aromatic inhibitors and trastuzumab/hesrceptin respectively, as documented in 5 pts (62%). The median time to progression these therapies are designed to target these molecules. FISH was 8.7 months (95% confidence interval 8-14 months). has proved to be a powerful molecular DNA technique in Conclusion: Intravenous administration of CET with HAI of pathology. Another technique that is used with increasing chemotherapy is feasible and has promising activity but is frequency is CGH. New technology using DNA microarrays associated with specific toxicity. provides a systemic method to identify key markers for prognosis and treatment response by profiling thousands of 5 genes expressed in a single tumor. Microarrays have the PATHOLOGY AS A BRIDGE potential to revolutionize the practice of pathology by BETWEEN RESEARCH AND CLINICAL PRACTICE providing a molecular “signature” that is characteristic of each neoplasm. Niki J. Agnantis All these new molecular pathology techniques are Department of Pathology, University of Ioannina Medical necessary, but they should be applied with caution. They School, Greece should be critically appraised and analyzed in detail regarding cost/benefit, in order to contribute the most to patient care. The word “Pathology” originates from the Greek words Pathos (suffering) and Logos (study) and, as its name implies, it is a 6 discipline devoted to the study of the cause, the pathogenesis, EFFECTS OF THERAPY WITH THE the morphological changes and functional derangement of RADIOLABELLED SOMATOSTATIN ANALOGUE cells, tissues and organs in disease. Anatomic pathology has [90Y-DOTA0,TYR3]OCTREOTATE IN PATIENTS WITH originated in Europe 245 years ago and it has come a long MENINGIOMA: REVIEW OF 16 CASES way since the time that Morgagni encouraged the postmortem M. Agostini1, F. De Lauro1, M. Casi1, V. Mattone1, search for the cause and nature of disease. During this long S. Severi1, C. Fabbri2 and G. Sarti2 course the histological techniques have been continuously improving and pathologists have been incorporating a variety 1Nuclear Medicine Unit, Imaging Department, M. Bufalini of methods in their every-day practice, making diagnosis more Hospital, viale Ghirotti 286, 47023 Cesena; refined and definite. Today, pathologists are able to make 2Health Physics, Imaging Department, M. Bufalini Hospital, diagnoses by examining a whole organ, a fragment of tissue, viale Ghirotti 286, 47023 Cesena, Italy or even a few cells. Advances in facing cancer range widely, from basic research designed to understand the molecular Aim: Therapy using the radiolabeled somatostatin analog [90Y- causes of cancer, through the application of this knowledge for DOTA0,Tyr3] octreotate (90Y DOTA-TOC) (DOTA is 1,4,7,10- the patients’ benefit. Both basic and clinical research, the latter tetraazacyclododecane-N,N’,N’‘,N’‘’-tetraacetic acid) has been being dependent on the former, are now developing at a fast used primarily in gastroenteropancreatic neuroendocrine pace. Pathology is the discipline that acts as a bridge between tumors. Here we present the effects of this therapy in a small Clinical Medicine and Basic Sciences. number of patients with meningiomas. In these patients the A classical paradigm on the role of the pathologist in basic therapy of choice is surgery and radiotherapy, however, the research is his contribution in elucidating the pathogenesis of presence of cellular structures for amine uptake and storage colorectal carcinoma. Every stage of adenocarcinoma allow targeted therapy. Meningiomas are tumors derived from development has been identified and the progressive cap cells adherent to the dura mater, mostly close to the accumulation of genetic changes at the molecular level has arachnoid villi or skull base foramina; they express different been shown to parallel the clinical and histopathologic kinds of receptors. Meningiomas are frequently somatostatin progression defined as “adenoma-carcinoma sequence”. receptor-positive, and somatostatin receptor scintigrafy may Another example is that of breast cancer. Subclassification be used to differentiate remnant or recurrent meningioma from of breast carcinomas is important, since some types such as non-specific hyperperfusion during postsurgical follow-up. tubular and medullary carcinomas, have better prognosis than Treatment with 90Y-labeled somatostatin analogs in patients others. However, the morphological features of the neoplasm with meningioma has been undertaken in selected cases. do not always reveal its underlying biology, as patients with Materials and Methods: We evaluated
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