Experimental, Clinical and Morphological Analysis of H-Ras Oncoproteins for Locally Advanced Breast Cancer.

BACKGROUND: Activated forms of Ras are enhanced in both breast cancer as well as the cell lines with EGFR and HER2 expression. Therefore, H-Ras could be activated in breast tumours in the absence of direct mutational activation of Ras itself and could contribute to 20-50% of the cases. Expression inhibition, signal transduction interruption from H-Ras to the nucleus could become a promising therapeutic target. AIM: The aim of this study was to investigate the clinical and morphological criteria of locally advanced breast cancer and the expression of H-Ras oncoprotein in patients who have been subjected to different regimens of farnesyltransferase inhibitor. METHODS: H-Ras status was assessed by immunohistochemistry (IHC). RESULTS: An association between the expressions of H-Ras and Her2/neu (p = 0.001) as well as the tumour proliferation index Ki-67 (p = 0.001) in patients with breast cancer was established. Analysis of the relationship between H-Ras expression showed a relatively strong association with progression-free survival both before the treatment (V = 0.47; p = 0.001) and after the treatment (V = 0.45; p = 0.001). These results may indicate the clinical applicability of H-Ras as a prognostic factor or serve as a therapeutic target for breast cancer treatment. CONCLUSION: These results could indicate the potential clinical application of H-Ras as a prognostic factor or a therapeutic target for breast cancer treatment.

NEOADJUVANT СHEMOTHERAPY FOR LOCALLY ADVANCED BREAST CANCER.

93 patients with LABC (T2N1-2M0, T3N0-2M0) at the age from 35 to 75 years were included in the trial. With 2 stage - 60 patients, with the third stage - 33 patients. All patients were randomized into 3 groups: The I control group (n=36) received 4 courses of neoadjuvant chemotherapy according to AC-protocol (doxorubicin 50 mg/m2, cyclophosphan-500 mg/m2 on day 1, repeated every three weeks) followed by radical mastectomy, 4 courses of adjuvant chemotherapy (АС), radiotherapy and hormone therapy if indicated. II investigative group (n=30) received the same CTX but in combination with Arglabin at a dose of 370 mg/m2 for 7 days. III investigative group (n=27) received Arglabin as monotherapy. The clinical efficacy of neoadjuvant chemotherapy according to the scheme of AC and AC + arglabin was the same and significantly exceeded Arlabine monotherapy. There was no statistically significant difference in pathological response in patients of all three groups. Arglabin has very low toxicity and eliminates the toxic effects of standard chemotherapy.

EPIDEMIOLOGY OF NEUROPATHIC CHRONIC PAIN IN ONCOLOGY PATIENTS.

The aim of the study was to analyze the primary prevalence of chronic neuropathic pain syndrome in oncology patients of Karaganda (Kazakhstan), to estimate the structure of pain syndrome in randomly chosen patients, to assess the effectiveness of analgesic therapy in oncology patients. All the patients with confirmed cancer admitted to hospital in Karaganda regional oncologic dispensary were studied. The study period was limited to 60 consecutive days. The results were statistically processed using 6.0 «STATISTICA¼ program. In 11,2±1,6% of the cases, oncology patients that got combined modality treatment suffered from the chronic neuropathic pain syndrome; 66,7±7,3% patients of them had the III cancer stage. 2. While studying the chronic neuropathic pain structure it was revealed that: 52,4±7,7% of the patients suffered from a mild pain, from average - 38,1±7,5% of the patients, from severe pain - 9,5±4,5%. Neuropathic pain syndrome in the form of numbness occurred in 47,6±7,7% of the respondents, tingling - in 38,1±7,5% of the patients and 14,3±5,4% of the respondents described it as «electric shock¼. 52,4±7,7% of the patients described temperature changes of the skin, 28,6±7,0% of them told about allodynia. The given pain can be correctly diagnosed on rare occasions. It brings about the low efficiency of currently prescribed standard pain treatment. It was 20%-effective only for » of the patients. In sum, it can be brought into focus that each 10th oncology patient of the II clinical group in Kazakhstan may potentially suffer from the chronic neuropathic pain syndrome. The given syndrome in cancer patients requires selective differential diagnostics and constant management of the pain treatment regimen because of occurrence of standard regimens incapacity, progression of tolerance to the actual pain treatment and significant deterioration of oncology patients' life quality.

THE IMPORTANCE OF IMMUNOHISTOCHEMICAL STUDIES IN THE DIAGNOSIS OF CANCER OF UNKNOWN PRIMARY ORIGIN.

The purpose of the research is to give a comparative diagnostic characteristic to tumors of unknown primary origin by admission diagnosis and morphological diagnosis. 162 treated cases with tumors of unknown primary at Oncologic Dispensary for 5 years were analyzed in details. Besides clinical, instrumental, cytological, morphological methods, immunnohistochemical research of tumors was carried out by avidin-biotin-peroxydase tecnics. The cases with poorly differentiated carcinoma (33,3±4,3%) and lymphoproliferative disorders (27,2±3,5%) prevailed among the cases with tumors of unknown primary by histological research. High degree of noncoincidence of cytologic and histological diagnoses (χ2=515, р=0,00001), histological and immunohistochemical diagnoses (χ2=378, р=0,00001), cytologic and immunohistochemical diagnoses (χ2=556, р=0,00001) were revealed. Cytologic overdiagnosis of undifferentiated carcinoma by 13,6% (р<0,05) and hypodiagnosis of benign diseases by 4,4% (р<0,05) and histological overdiagnosis of poorly differentiated carcinoma by 11,1% (р<0,05) and hypodiagnostics of tumors of nerve tissue by 8,0% (р<0,05) are marked, that points to the necessity of making immunohistochemical research in the cases of given pathology. Statistically significant connection of mean degree between diagnoses of poorly differentiated tumors made by cytologic, histological and immunohistochemical investigation is revealed.