[Impact of preoperative drug therapy on the expression of angiogenesis markers in colorectal liver metastases]. / Vliyanie predoperatsionnoi lekarstvennoi terapii na ekspressiyu markerov angiogeneza v metastazakh kolorektal'nogo raka v pecheni.

AIM: to study changes in the expression of angio- and vasculogenesis markers in colorectal adenocarcinoma metastases to the liver during combined cytotoxic and targeted anti-VEGF therapy versus cytotoxic monotherapy. SUBJECTS AND METHODS: Intraoperative samples from 96 patients with colorectal adenocarcinomas metastases to the liver were immunohistochemically examined. The investigation enrolled patients who had preoperatively received either combined FOLFOX6 cytotoxic therapy and targeted anti-VEGF therapy with bevacizumab or only FOLFOX6 therapy, as well as patients who had not received preoperative anti-tumor drug treatment. The expression of SDF1α, CXCR4, CXCR7, and VEGF-A was compared in these groups. Statistical significance was accepted at p<0.05. RESULTS: The expression of CXCR4 in the vessel endothelial cells was significantly less frequently detected in the patients who had received combined cytotoxic therapy and targeted anti-VEGF therapy as compared to those had not drug therapy. Comparing the patients treated with cytotoxic drugs with those who had not received anti-tumor therapy revealed similar results in the women. CXCR7 expression in the tumor cells and stromal cells from the metastatic foci was significantly more common in the group of male patients treated with cytotoxic drugs according to the FOLFOX6 regimen. The expression of SDF1α in the tumor cells was significantly more often observed in the male patients who had received combined cytotoxic therapy and targeted anti-VEGF therapy than in those who had not drug therapy. VEGF expression in the stromal cells was significantly less frequently seen in the patients who had received the combined therapy. CONCLUSION: Combined cytotoxic therapy and targeted anti-VEGF therapy for colorectal adenocarcinoma metastases to the liver leads to some suppression of the alternative pathway in the formation of new vessels, by reducing the expression of CXCR4 in the vessel endothelial cells and that of VEGF in the stromal cells from the metastatic foci. In men, this therapy simultaneously causes an increase in the expression of SDF1α in the tumor cells and in that of CXCR4 in the stroma. Preoperative FOLFOX6 therapy significantly increases the expression of CXCR7 in the tumor cells and stromal cells in the male patients, which may suggest that this pathway in vessel formation can be activated.

[Mucinous cystic liver tumors: diagnosis and surgical treatment]. / Mutsinoznye kistoznye opukholi pecheni: diagnostika i khirurgicheskoe lechenie.

AIM: To optimize diagnostics and treatment of cystic liver tumors. MATERIAL AND METHODS: The analysis included outcomes of 46 patients with liver cystic tumors. RESULTS AND DISCUSSION: The use of abdominal Doppler-sonography (37 patients), abdominal contrast-enhanced CT (44 patients) and MRI of abdominal cavity with MR-cholangiography (24 patients) defined radiological semiotics of cystic liver diseases. The most important features of cystic tumors are intraluminal septums with blood flow (82% of patients), solid component (6.8%), daughterly cysts (11.3%), as well as biliary hypertension (39.2% of patients). Research of oncomarkers (CEA, SA 19-9, AFP) in 40 patients showed increased level of SA 19-9 only in case of cystadenocarcinoma and intraductal papillary mucinous neoplasm of biliary type. Benign and malignant cystic tumors had increased contents of oncomarkers in all cases. Surgical treatment was used in 42 patients. Extended liver resections were performed in 10 (23.8%) patients, atypical and anatomical resections (removal of less than 3 segments) - in 31 (73.8%) patients. In one case we applied cryoablation of CA in segment I of the liver in view of invasion into the wall of inferior vena cava and hepatoduodenal ligament. In 2 cases surgery was carried out laparoscopically. Also robot-assisted technique was used in 3 patients. Immunohistochemical study was performed in 22 (44.8%) patients. The diagnosis of CAC and biliary type of IPMN was confirmed in case of high expression of CK7, SK19, MUC1, S100p, SDH2, p53 antibodies. Cystadenomas were associated with moderate expression of ER, PR and p53 antibodies by stroma and CK7, SK19, CDX2, MUC1, S100p antibodies by epithelium. CONCLUSION: There are considerable difficulties of differential diagnosis of liver cystic tumors. Therefore, the use of single algorithm of diagnostics and treatment is necessary to confirm accurately the diagnosis at the perioperative stage. Cystic tumor is more likely to be assumed in women with solitary cyst in segment IV of liver. If the diagnosis is suspected or confirmed anatomical liver resection with complete tumor removal is necessary to prevent the recurrence.

Composite glycerol/graphite/aromatic acid matrices for thin-layer chromatography/matrix-assisted laser desorption/ionization mass spectrometry of heterocyclic compounds.

New composite matrices have been suggested for the analysis of mixtures of different synthetic organic compounds (N-containing heterocycles and erectile dysfunction drugs) by thin layer chromatography/matrix-assisted laser desorption ionization time-of-flight mass spectrometry (TLC/MALDI-TOF). Different mixtures of classical MALDI matrices and graphite particles dispersed in glycerol were used for the registration of MALDI mass spectra directly from TLC plates after analytes separation. In most of cases, the mass spectra possessed [M+H]+ ions; however, for some analytes only [M+Na]+ and [M+K]+ ions were observed. These ions have been used to generate visualized TLC chromatograms. The described approach increases the desorption/ionization efficiencies of analytes separated by TLC, prevent spot blurring, simplifies and decrease time for sample preparation.

[Contrast-enhanced computed tomography is the required minimum in the diagnosis of abdominal and retroperitoneal space-occupying lesions].

OBJECTIVE: to determine the advantages of contrast-enhanced computed tomography (CT) over contrast-free studies in the differential diagnosis of hepatic, renal, and pancreatic space-occupying lesions. MATERIAL AND METHODS. A team of experienced radiologists retrospectively used CT data of patients with different space-occupying lesions of the abdomen and retroperitoneal space (liver, kidney, and pancreas). RESULTS: The diagnostic value of CT of the liver, kidney, and pancreas substantially decreases without using radiopaque contrast agents; at the same time not only the differential diagnosis, but also visualization of some neoplasms are frequently impossible. CONCLUSION: The potential benefit of contrast-enhanced CT virtually always outweighs the risks associated with the injection of a contrast agent.

[Impact of preoperative drug therapy on the expression of apoptosis markers in colorectal liver metastases].

AIM: to estimate the expression of p53 protein, effector caspases-3 and -7, and the antiapoptotic protein survivin in colorectal adenocarcinoma metastases to the liver in patients who have received preoperative cytotoxic and combined cytotoxic and target anti-VEGF therapies. SUBJECTS AND METHODS: Intraoperative samples from 122 patients with colorectal carcinoma metastases to the liver were immunohistologically examined. The investigation included patients who had received preoperative treatment with cytotoxic drugs, combined cytotoxic and targeted anti-VEGF therapy. A control group consisted of patients who had not received preoperative anti-tumor drug treatment. RESULTS: Expression of Caspase 3, including that of survivin, was significantly more frequently detected in the patients who had received combined cytotoxic and anti-VEGF therapy as compared to both those treated with only cytotoxic agents (p=0.00004) and the control group (p=0.0008) As compared to the latter, the women who had received cytotoxic therapy were found to have no survivin expression (p=0.015). Investigation of the expression of caspase-7 and p53 revealed no statistically significant differences between the three groups. CONCLUSION: Addition of bevacizumab to preoperative standard therapy regimens for colorectal adenocarcinoma metastases to the liver leads to activated apoptosis in tumor cells, by enhancing the expression of effector caspase 3. At the same time, standard cytotoxic chemotherapy regimens in women results in activated apoptosis, by decreasing the expression of the antiapoptotic protein survivin.

[Influence of the antihypoxantic therapy on children with generalized peritonitis]. / Vliyanie antigipoksantov na rezul'taty lecheniya rasprostranennogo peritonita u detei.

AIM: To improve the results of treatment of a widespread purulent peritonitis in children by optimizing fluid therapy includes the use of combined treatment: reamberin and remaxol. MATERIAL AND METHODS: We studied 269 patients aged 1 to 15 years with a widespread purulent peritonitis treated at the children's surgical departments in Samara from 2001 to 2015. The study group included 179 children who used the optimized infusion therapy. In the study group was allocated to 2 groups: 69 children in infusion therapy which used reamberin and 110 patients in which treatment was applied reamberin and remaxol. The surgical treatment used laparoscopic sanation of the abdomen. Comprehensive survey included a study of dynamics of the white blood cell count, leukocyte index Kalf-Caliph, erythrocyte sedimentation rate, temperature, total albumin concentration, transaminase levels. Catamnesis studied 48 patients with the definition of complex intima-media thickness in the projection of basilar, brachial and femoral arteries. RESULTS: A study compared indicators of both groups, revealed a more rapid reduction of intoxication symptomps (leukocytosis, LII, body temperature), the disappearance of enteric disease, recovery of protein-synthetic function of the liver, decrease of cytolytic and mesenchymal-inflammatory syndromes in the main group, especially in the subgroup in which treatment was included remaxol. CONCLUSION: The use of reamberin and remaxol in infusion therapy led to improvement of the results of the treatment of common purulent peritonitis in children. Study catamnesis with the study of the intima-media revealed that children undergoing widespread purulent peritonitis further develop signs of endothelial dysfunction. The developed clinical recommendations to significantly reduce the risk of developing signs of endothelial dysfunction, thereby reducing the possible appearance of vascular pathology in patients who underwent childhood widespread purulent peritonitis.

[Impact of preoperative drug therapy on adhesion molecule expression in colorectal cancer liver metastases].

OBJECTIVE: To study E-cadherin and ß-catenin expression in colorectal cancer (CRC) liver metastases in order to assess the impact of different drug therapy regimens on the adhesive properties of tumor cells. MATERIAL AND METHODS: Intraoperative metastatic CRC samples from patients who had received preoperative cytotoxic chemotherapy or combined cytotoxic and targeted anti-VEGF (vascular endothelial growth factor) therapy were immunohistochemically examined using antibodies to E-cadherin and ß-catenin. A comparison group consisted of patients who had not received drug therapy. RESULTS: Combined therapy with cytotoxic and anti-VEGF agents was shown to result in a significant increase in the number of cases of normal membrane localization of E-cadherin as compared with control (p = 0.00043) and cytotoxic therapy-alone (p = 0.01) groups. A comparison of ß-catenin levels in three patient groups revealed no significant differences, but addition of an anti-VEGF agent caused some decrease in the number of cases of abnormal nuclear localization of the protein as compared to both the control group and the cytotoxic therapy groups. The comparison of E-cadherin and ß-catenin localization in tumor cells showed that a combination of normal E-cadherin membrane localization and ß-catenin membrane-cytoplasmic expression prevailed in the combined therapy group compared to the control (p = 0.009) and cytotoxic therapy (p = 0.04) groups. CONCLUSION: The addition of a targeted anti-VEGF agent to the drug therapy of metastatic CRC has a positive impact on the cadherin-catenin complex, leading to increased intercellular contacts and suppressed ß-catenin functioning as a transcription factor that enhances tumor cell proliferation.

[Treatment of diffuse peritonitis in children].

THE PURPOSE OF THE STUDY: Improving the treatment of advanced peritonitis via use in therapy antihypoxant Reamberin and hepatoprotector Remaxol, nutritional support, sanitation laparoscopic abdominal cavity. SUBJECTS: A total of 232 children aged 1 to 15 years with generalized purulent peritonitis treated at the children's surgical departments of Samara from 2001 to 2014. A study group comprised 148 patients who used the optimized pathogenetic therapy. In the study group was allocated two groups: 64 patients in the pathogenetic therapy that used antihypoxant reamberin, and 84 children in the treatment of which reamberin and hepatoprotector remaxol. All the children of the main group received nutritional support (trophic feedings), used in the surgical treatment of abdominal laparoscopic sanitation. Comprehensive survey includes the study of the dynamics of the level of white blood cells, leukocyte index on Kalf-Caliph, erythrocyte sedimentation rate, temperature, total albumin concentration, transaminase levels. RESULTS: Comparison of the studied parameters in the study and control groups, showed a more rapid decrease in the symptoms and signs of intoxication (leukocytosis, LII, body temperature), relief of enteric disease, recovery of protein-synthetic function of the liver, a decrease of cytolytic and mesenchymal-inflammatory syndrome in the study group, especially in the subgroup in which therapy was included remaxol. CONCLUSIONS: Optimization of treatment involving the application of the combined drugs--antihypoxant reamberin, hepatoprotector remaxol, nutritional support and implementation of laparoscopic abdominal sanitation led to improved results of therapy common purulent peritonitis in children.

[Comparative study of effect of infrared, submillimeter, and millimeter electromagnetic radiation on wing somatic mutations in Drosophila melanogaster induced by gamma-irradiation]. / Sravnitel'noe issledovanie vliianiia élektromagnitnogo izlucheniia infrakrasnogo, submillimetrovogo i millimetrovogo diapazonov na indutsirovannye gamma-oblucheniem somaticheskie mutatsii kletok kryl'ev Drosophila melanogaster.

It was shown that the number of spontaneous and gamma-radiation-induced somatic mutations in wing cells of fruit flies (third instar larvae) exposed to laser irradiation of submillimeter range (lambda = 81.5 microns) was significantly lower than in control. Laser irradiation did not affect the number of recombinations. Exposure to laser radiation in the infrared range and electromagnetic waves of the millimeter range (lambda = 3.8 mm) enhanced the effect of gamma-irradiation.

Pyrrolo[3,2-c]pyridine derivatives as inhibitors of platelet aggregation.

A series of pyrrolo[3,2-c]pyridines, isosteres of the antithrombotic drug ticlopidine, has been synthesized and evaluated in vitro for the ability to inhibit aggregation of human platelet-rich plasma induced by adenosin 5'-diphosphate (ADP). Structure-activity relationships showed their antiplatelet effects to be related to the lipophilicity.