ASSOCIATION OF miRNA EXPRESSION PATTERN WITH OUTCOME OF LETROZOLE THERAPY IN BREAST CANCER PATIENTS.

Breast cancer (BC) remains the most prevalent tumor and the leading cause of death among women worldwide, despite the advancements in diagnosis and new treatments. A significant challenge in BC treatment is the acquired or de novo resistance of tumors to systemic therapy. To overcome this obstacle, personalized treatment is needed, with a focus on finding biomarkers capable of predicting the response to therapy. MicroRNAs (miRNAs) have emerged as potential markers due to their diverse clinical applications. AIM: To examine the potential prognostic significance of miR-125b-2, -155, -221, and -320a expression in the tumor cells of individuals with hormone-dependent BC before undergoing neoadjuvant hormonal therapy. MATERIALS AND METHODS: The study is based on a retrospective analysis of the treatment outcome of 56 patients with stage II-III locally disseminated hormone-dependent BC. The real-time quantitative reverse transcription polymerase chain reaction was performed on the biopsy material to assess the expression of miR-125b-2, -155, and -221 before neoadjuvant hormonal therapy with aromatase inhibi- tor letrozole to predict clinical response. RESULTS: Most HER2/neu+ BC patients had low levels of miR-155 and miR-221 expression in tumor biopsy specimens. Tumors that responded well to letrozole exhibited lower levels of miR-125b-2 and miR-221 compared to non-responsive tumors. CONCLUSIONS: miR-125b-2, -155, and -221 expres- sion can predict resistance to the letrozole treatment of BC.

EXPRESSION PATTERN OF miR-125b-2, -155, -221, AND -320a IS ASSOCIATED WITH RESPONSE OF BREAST CANCER PATIENTS TO TAMOXIFEN.

BACKGROUND: Hormonal therapy is one of the main methods of comprehensive treatment of patients with locally advanced breast cancer (BC). Despite the intensive search for molecules associated with the aggressiveness of the tumor process, currently there are no reliable markers predicting response to neoadjuvant hormonal therapy (NHT). AIM: To investigate the correlation between miR-125b-2, -155, -221, -320a expression in tumor tissue and HER2/neu status and response to tamoxifen treatment in BC patients. MATERIALS AND METHODS: Expression levels of miR-125b-2, -155, -221, and -320a were analyzed in biopsy samples of 50 BC patients using a real-time polymerase chain reaction. RESULTS: We found that levels of miR-125b-2, -155, -221, and -320a were 1.72, 1.65, 1.85, and 2.89 times higher in BC biopsy samples expressing estrogen/progesterone receptors and HER2/neu compared with HER2/neu-negative luminal tumors. Patients with a luminal BC showing higher levels of miR-125b-2 and miR-320a expression before therapy demonstrated better response to NHT with tamoxifen. A strong correlation was calculated for miR-221 expression and response to NHT (r = 0.61). CONCLUSIONS: The high levels of miR-125b-2, -155, -221, and -320a in tumor tissue are associated with the HER2/neu-positive status of luminal BC subtypes. Tumor samples of patients showing the low response to NHT with tamoxifen are characterized by lower expression of miR-125b-2 and -320a. Hence, miR-125b-2 and -320a could be considered as putative predictive biomarkers associated with tamoxifen sensitivity of hormone-dependent BC.

FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma.

BACKGROUND: Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. PATIENTS AND METHODS: The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/m2 then 600 mg/m2 Q3W) (arm 2, n = 77). Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m2 Q3W, n = 85). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. RESULTS: In the overall population, both PFS [hazard ratio (HR) = 0.44; 95% confidence interval (CI), 0.29-0.67; P < 0.0005] and OS (HR = 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab + EOX (arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells (HR = 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR = 0.58; 95% CI, 0.39-0.85; P = 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone). CONCLUSIONS: In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab + EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m2 is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells.

DENTAL STATUS FEATURES IN PATIENTS DURING ANTI-CANCER CHEMOTHERAPY (TRANSCARPATHIAN ANTITUMOR CENTER EXPERIENCE).

One of the most common complications of complex anticancer therapy is the development of various lesions of the oral cavity, including mucositis, which adversely affects the quality of life of the patient, limits the dose of chemotherapy and radiotherapy, and further adversely affects the effectiveness of complex therapy. Objective - to investigate the dental status of patients who are in anticancer chemotherapy and radiotherapy through clinical examination and calculation hygienic indices. During the study, the oral cavity was examined in 130 patients from 2015-2020, during the examination the dental status was registered and complaints were recorded. The dental status of patients on antitumor chemotherapy and radiotherapy by the method of clinical examination and calculation of hygienic indices (CSR (caries: sealed: removed), CPI index, Green Vermilion index, Fedorov-Volodkina index) was studied. A clinical examination of the oral cavity of patients who were on anticancer therapy in a cancer hospital revealed that the patients had poor oral hygiene and needed specialized dental treatment. Burning of the oral mucosa was present in 92.3% of patients, paresthesia - in 97.7%, taste disturbance and xerostomia - in all patients. In 30.0% there was angular cheilitis, in 96.2% bleeding gums, pus from periodontal pockets in - 17.7%, the formation of ulcers of the oral mucosa - 63.9%, mouth opening disorders - in 19.2%. The need for dental care was in 13.1% of patients in the study group. During the year before hospitalization, patients had 0.8±0.4 visits to the dentist per year, rarely used additional personal hygiene products for oral care - in 9.2%. The results indicate the presence of oral problems in 100.0% of patients receiving specialized antitumor chemotherapy and radiotherapy, as well as the presence of a sufficiently high need for specialized dental treatment.

[BIOLOGICAL HERMETICITY, MECHANICAL STRENGTH AND MORPHOLOGICAL CHARACTERISTICS OF ONE-ROW AND TWO-ROW COLON ANASTOMOSES].

Aim - comparison of biological hermeticity, mechanical strength and differences in morphological characteristics of one-row and two-row colon anastomoses. 20 animals were used in the experiment. Rabbits of both sexes aged from 8 months to 1.5 years and weighing from 1.5 to 2.6 kg were used as experimental animals. The animals were divided into experimental and control groups. In the experimental group we used the developed technique of one-row colon anastomosis (CA) formation, in the control group - the traditional two-row CA. Assessment of mechanical strength was performed by using the original method of pneumopression of colon segment with the anastomosis. The biological hermeticity was assessed by culturing flushing water from the anastomosis line to growth medium. The morphological picture was evaluated by microscopy of histological samples from the anastomosis line. The mechanical strength of the one-row anastomosis, compared with the traditional two-row, was higher at each stage of the study, on the first day by 66.3%, the third - 87.6%, the fifth - 76.1%, the seventh - 85.4%. The formation of a one-row CA allowed to achieve biological hermeticity of the anastomosis area in all periods of the early postoperative period, and when using a double-row suture, the anastomosis area became sterile only from 5 day. Morphologically, the picture was characterized by inflammatory processes in the anastomosis area when using the original technique, which were stopped in 3-5 days, and in the control group they persisted for up to 7 days, accompanied by vascular paresis of the intestinal wall, blood stasis and blood clots, with zones of mucosal necrosis at 3 and 5 day of observation.

Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

PURPOSE: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures. METHODS: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year. RESULTS: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs. CONCLUSION: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.

[Radical nephrectomy and thrombectomy in patients with renal cell cancer complicated by tumoral thrombosis of the renal vein and vena cava inferior].

Surgical treatment was conducted in 81 patients, suffering renocellular cancer (RCC), complicated by a renal vein and vena cava inferior thrombosis. According to the Mayo clinic classification, the level of a tumoral thrombus spread was established: the 0 level--in 37 patients, the level I--in 19, the level II--in 17, the level III --in 6, and the level IV--in 2. There were substantiated the optimal surgical accesses and technique of radical nephrectomy and thrombectomy for RCC, complicated by a renal vein and vena cava inferior thrombosis. It is recommended to apply transabdominal accesses: the extended median laparotomic, bilateral subcostal of a "Chevron" or "Mercedes" type. There was shown, that the access choice depends on the level of the tumoral thrombus localization.

[Indices of the external respiratory function in patients suffering from hepatic cirrhosis with ascitic syndrome].

The changes of external respiration indices in the patients suffering hepatic cirrhosis, complicated by ascitis and portal hypertension, were studied. Application of method of the ascitic liquor extracorporeal ultrafiltration and sorption with its subsequent return into venous system was proposed. The morphological changes of pulmonary parenchyma, which coincided with lowering of the external respiration indices in the patients, were studied.

[Classification of arterial reocclusion of the femoro-popliteo-tibial segment for the choice of the reconstruction method].

The literature data, concerning the issues of terminology and classification of occlusion and reocclusion of the femoro-popliteo-tibial segment arteries were analyzed. Basing on analysis of the results of clinico-instrumental investigations performed, classification of the femoro-popliteo-tibial segment arteries reocclusion was proposed, which it is expedient to apply while making choice of the rereconstruction method.

[Albumin-mediated peritoneal dialysis as method of restorational therapy in hepatic insufficiency].

New method of extracorporeal detoxication of organism, which is applied for temporary restoration of hepatic detoxication function in patients with hepatic insufficiency, albumin-mediated peritoneal dialysis, was presented. The main principle of this technology is a transfer through highly permeable dialysis membrane of toxins, which are in affinity with albumin, from the blood to acceptor. The donor's human albumin, circulating in the closed contour, serves as acceptor. The watersoluble lowmolecular substances are excreted according to the concentration gradient. For rapid restoration of acceptoral ability of the donor's albumin solution it was subjected to hemodialysis and carboperfusion. The performance of the procedure guarantees excretion of toxins, combined with albumin, along with excretion of watersoluble toxins.

[Surgical treatment of chronic venous insufficiency]. / Khirurhichne likuvannia khronichnoï venoznoï nedostatnosti.

Results of surgical treatment of 700 patients with chronic venous insufficiency of the lower extremities are presented. Subfascial endoscopic ligature of perforating veins and catheteric truncal sclerotherapy of v. saphena magna was applied by the authors side by side with traditional operations--venectomy and ligature of perforating veins. In the patients, treated using miniinvasive methods, the lowest frequency of purulent postoperative complications, the veins varicosis and the trophic ulcers recurrence was registered. Good immediate and late follow-up results achieved are due to meticulous selection of patients depending on the venous insufficiency stage and the deep venous system passability. It is necessary to proceed with further investigation of possibilities of the perforating veins endoscopic subfascial ligature and of catheteric truncal sclerotherapy performance in other stages of the disease.

[The ultrasonographic confirmation of the role of external carotid artery in blood supply of ischemic lesion in the big cerebral hemisphere]. / Dopplerohrafichne pidtverdzhennia znachenia zovnishn'o]i sonnoï arteriï v krovopostachanni ishemizovannoï pivkuli velykoho mozku.

Using intraoperative monitoring of the blood flow linear speed in a. cerebralis media while total a. carotis interna occlusion in 10 patients the authors have concluded, that the degree of blood flow compensation in a. cerebralis media depends not only on collateral compensation possibilities by the contralateral side and rate of it inclusion, but largely-on a. carotis externa possibility on the lesion side.