Irreversible Electroporation in Pancreatic Cancer-An Evolving Experimental and Clinical Method.

Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with early metastasis. Up to now, the only curative treatment is surgical resection, which is possible in the early stages of the disease. Irreversible electroporation treatment offers new hope for patients with unresectable tumors. Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer. Ablation therapies involve the use of energy to destroy or damage cancer cells. IRE involves using high-voltage, low-energy electrical pulses to create resealing in the cell membrane, causing the cell to die. This review summarizes experiential and clinical findings in terms of the IRE applications. As was described, IRE can be a non-pharmacological approach (electroporation) or combined with anticancer drugs or standard treatment methods. The efficacy of irreversible electroporation (IRE) in eliminating pancreatic cancer cells has been demonstrated through both in vitro and in vivo studies, and it has been shown to induce an immune response. Nevertheless, further investigation is required to assess its effectiveness in human subjects and to comprehensively understand IRE's potential as a treatment option for pancreatic cancer.

Micro- and Nanosecond Pulses Used in Doxorubicin Electrochemotherapy in Human Breast and Colon Cancer Cells with Drug Resistance.

(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20-900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols' efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment.

Case report laparoscopy-assisted pre-pubic urethrostomy as a palliative procedure for resection of distal urethral tumor in a female dog.

BACKGROUND: This paper presents the first described case of laparoscopy-assisted prepubic urethrostomy and laparoscopic resection of a tumor of the distal part of the urethra in a female dog as a palliative treatment. CASE PRESENTATION: An intact, 11 -year-old, mixed breed female dog, weighing 15 kg, was admitted with signs of urinary obstruction and difficulty with catheterization. Vaginal, rectal, and endoscopic examinations revealed a firm mass in the pelvic cavity at the level of the pelvic urethra. Ultrasound and computed tomography examination showed enlargement of the urethral wall (5.5 cm width and 3 cm thick), which was significantly restricting the patency of the urethra. The lesion affected only the distal part of the urethra without the presence of local or distant metastatic changes. The affected portion of the urethra was laparoscopically removed while performing pre-pubic urethrostomy with laparoscopy. The patient regained full consciousness immediately after the end of anesthesia, without signs of urinary incontinence. Histopathological examination of the removed urethra revealed an oncological margin only from the side of the bladder. In the period of 2.5 months after the procedure, the owner did not notice any symptoms that could indicate a postoperative recurrence, which was diagnosed three months after the procedure. CONCLUSIONS: Pre-pubic urethrostomy can be successfully performed with the assistance of laparoscopy. The use of minimally invasive surgery will allow, in selected cases, removal of the urethral tumor, and in inoperable cases, to perform a minimally invasive palliative pre-pubic urethrostomy.

A review on Eph/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers.

Erythroprotein-producing human hepatocellular carcinoma receptors (Eph receptors) compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins (Ephrins) are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes. Moreover Eph/ephrin system is one of the crucial ones in angiogenesis and lymphangiogenesis. With such a wide range of impact it is clear that disturbed function of this system leads to pathology. Eph/ephrin system is involved in carcinogenesis and cancer progression. Although the idea of participation of ephrin in carcinogenesis is obvious, the exact way remains unclear because of complex bi-directional signaling and cross-talks with other pathways. Further studies are necessary to find a new target for treatment.

Disrupted Balance of MMPs/TIMPs in Gastric Carcinogenesis-Paradoxical Low MMP-2 Expression in Tumor and Stromal Compartments as a Potential Marker of Unfavorable Outcome.

The aim of the study was to find correlations between MMP/TIMP reactivity and the expression of angiogenic factors, and relationships between these parameters and clinicopathological features of gastric cancer patients. Receiver Operating Characteristic curve analysis was used to find cut-off points that enabled fair decision-making in survival analysis. Low levels of MMP-2 expression in tumor and stromal compartments were significantly associated with poor prognosis-the probability that a patient would die within 60 months of surgery if their MMP-2 was low, and was about 0.8 in both neoplastic and stromal compartments.

Lymphangiogenesis in early and advanced gastric cancer: is there any difference?

BACKGROUND AND AIM: Gastric cancer (GC) in Poland is on the third place of men's mortality and on the fifth place of women's mortality in malignant neoplasms, and the percentage of diagnosed early GC is less than 20%. In this study, the relationship among lymphatic vessel density, marked with D2-40, expression of vascular endothelial growth factor (VEGF)-C/D, VEGF receptor 3 VEGFR-3, and the stage of GC patient were investigated. METHODS: This study examined the relationships between the peritumoral lymphatic vessels (PTL) density and intratumoral lymphatic vessels (ITL) density stained immunohistochemically with D2-40/podoplanin, the expression of VEGF-C/D and VEGFR-3, and the stage of 58 GC patients. RESULTS: Lymphatic vessel density measured by D2-40 decreases outside the tumor (PTL) and increases within the tumor (ITL) as the staging grows from I to III, whereas in the case of patients belonging to stage IV group, lymphatic vessel density decreases outside the tumor as well as within the tumor in comparison with the stage III group (not statistically significant). We observed a difference between morphology of the vessels within the tumor (ITLs) and vessels that are located outside the tumor (PTLs). PTLs were enlarged and unsqueezed as opposed to ITLs, which were collapsed. CONCLUSIONS: (i) There is no significant correlation between the density of ITL nor PTL marked with D2-40 and the stage of GC. (ii) We did not observe relationship between expression of VEGF-C/D and VEGFR-3 and the stage of GC. (iii) Further studies are needed to fully determine the role of PTL and ITL.

High density of peritumoral lymphatic vessels measured by D2-40/podoplanin and LYVE-1 expression in gastric cancer patients: an excellent prognostic indicator or a false friend?

BACKGROUND: One of the most important prognostic indicators in gastric cancer is the presence of metastases in lymph nodes. Even now, little is known about lymphangiogenesis in neoplastic tissue, and little is also known about the transmission of a neoplastic cell from the tumor mass into a lymphatic vessel. METHODS: This study examined the relationships between the density of lymphatic vessels (LVD) stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and D2-40 (podoplanin) antibodies, the expression of vascular endothelial growth factor (VEGF)-C/D, selected clinical and pathomorphological factors, and the 5-year overall survival of gastric cancer patients. RESULTS: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels. Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045). CONCLUSION: The study showed that the studied markers cannot be used to determine the required extent of the surgical procedure, as they have no statistically significant correlation with the degree of progression of the cancer, the stage of the disease assessed according to the TNM 5th classification of malignant tumors, clinicopathological features, and patient survival. VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

[Difficult and unusual diagnostic and therapeutic gastric Schwannoma case]. / Trudny i niecodzienny przypadek diagnostyczno-leczniczy--Schwannoma zoladka.

Schwannoma is a rare, usually benign, generally slow growing, asymptomatic mesenchymal neoplasm derived from nerve cells. In the gastrointestinal tract the most common localization is stomach and the gastric schwannomas represent about 0.2% of all gastric neoplasms. We present a case of 44-years-old male admitted to 2nd Department of General Surgery and Oncological Surgery Medical University for treatment of a submucosal gastric tumor detected in upper gastrointestinal endoscopy, endoscopic ultrasonography and computed tomography (CT). Patient presented with no gastrointestinal disorders and the random endoscopy revealed a gastric tumor, but the biopsy of the lesion showed no carcinomas' cells and the suspicion of GIST. CT confirms the presence of the 5 cm large gastric tumor and intraabdominal lymphadenopathy. The patient was directed to surgery because of the malignant risk. The subtotal gastrectomy with BII anastomosis was performed and no perioperative complications were observed. The postoperative histopathological examination revealed a typical morphology and immunophenotype of tumor. The neoplastic cells were immunoreactive with S-100 protein, but lacked immunoreactivity with CD 117, CD 34 and smooth-muscle actin (SMA). The histopathologic features and immunohistochemical staining pattern were consistent with a gastric schwannoma. The lymph nodes resected, during the operation revealed reactive inflammatory changes without evidence of neoplastic cells and any malignancy. 10-month after the surgery patient has no complains but the follow up will be continued. This case underscores the importance of including gastric schwannomas in the differential diagnosis when preoperative imaging studies reveal a submucosal, exophytic gastric mass.

HER-2 expression in immunohistochemistry has no prognostic significance in gastric cancer patients.

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4-12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P = 0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient's age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.

Predicting the chemosensitivity of pancreatic cancer cells as a personalized therapy.

BACKGROUND: Annually, approx. 4000 patients are diagnosed with pancreatic cancer in Poland, and the number of deaths is close to the number of diagnoses. Such a high morbidity/mortality ratio is caused by a high percentage of unresectable lesions (about 80%) and chemoresistance, which, among other things, is due to the specific desmoplastic environment. Currently, there are 2 main systemic treatment regimens for pancreatic cancer: FOLFIRINOX (which is a combination of folic acid, fluorouracil (5-FU), irinotecan, and oxaliplatin) and combined treatment with nab-paclitaxel plus gemcitabine (NPXL+GMC). OBJECTIVES: In order to increase the effectiveness of systemic treatments for individual patients, cell lines derived from resected pancreatic tumors were developed and their chemosensitivity to various agents was examined. The hypothesis was that patients may benefit from individualization of chemotherapy. MATERIAL AND METHODS: Patients with histopathologically confirmed pancreatic cancer were operated on using irreversible electroporation (IRE) procedure. After isolating and establishing individual cell lines, chemosensitivity to 5-FU, GMC and NPXL was determined using MTT assay in primary and metastatic cell cultures. RESULTS: Three primary cell lines were isolated for the prediction of chemosensitivity. Gemcitabine was shown to be more effective at lower doses compared to 5-FU, while NPXL was more effective than 5-FU, and both of these were less effective in metastatic cells. Pancreatic cancer cell chemoresistance was confirmed in stage IV. CONCLUSION: Determination of chemosensitivity profiles using cell lines may help in the selection of systemic treatments for individual patients. This method can be the basis for a personalized planned chemotherapeutic protocol.

Effects of calcium electroporation, electrochemotherapy, and irreversible electroporation on quality of life and progression-free survival in patients with pancreatic cancer: IREC clinical study.

BACKGROUND: According to the National Cancer Registry, 3486 people (1744 men and 1742 women) were diagnosed with pancreatic adenocarcinoma in Poland in 2018, resulting in 4908 deaths (2396 men and 2512 women). The only chance of successful treatment is through surgical resection, which is possible in only 20-30% of patients (stage I, II and some stage III cases).The remaining 70-80% of patients are those with stage III and IV disease, for whom resection is not possible. Mean survival in these patients is approx. 10.4 months (stage III). In the recent decade, an innovative method called electroporation, which involves destabilization of the cell membrane, has been established. This process can be reversible (RE) or irreversible (IRE), and leads to cell death. The ability to change membrane permeability has led to the development of novel methods involving electrochemotherapy (ECT) and calcium electroporation (CaEP) to treat solid tumors. OBJECTIVES: In this study, both ECT and CaEP will be used to treat pancreatic cancer patients with poor prognosis. For each patient, the best "therapeutic moment" for the procedure will be selected based on the therapeutic protocol. MATERIAL AND METHODS: Patients will receive reversible and irreversible electroporation (control arm-group A), CaEP (active arm-group B), or ECT with intravenous and intratumoral administration of bleomycin (active arm-group C) randomized 1:1:1. RESULTS: The primary endpoints will be progression-free survival (PFS) and patients' quality of life (QOL) assessed using the EORTC-PAN 26 scale. Secondary endpoints will be patient overall survival (OS), body weight, pain level, and levels of biomarkers such as Ca 19-9. CONCLUSION: The Irreversible Electroporation, ELectrochemotherapy and Calcium electroporation (IREC) study is necessary to examine the safety and efficiency of irreversible electroporation, electrochemotherapy and calcium electroporation in pancreatic cancer treatment.

Modulation of Blood-Brain Barrier Permeability by Activating Adenosine A2 Receptors in Oncological Treatment.

The blood-brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood-brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy.

The sense of coherence and sense of satisfaction with life in patients hospitalized in Polish and Irish surgical departments.

BACKGROUND: The concept of the sense of coherence (SOC) - the global orientation of life, created by Aaron Antonovsky - is increasingly popular. This study within the field of health psychology examines the situation of patients awaiting surgery in Poland and Ireland. OBJECTIVES: To investigate the relationship between the strength of the SOC and its components (comprehensibility, manageability and meaningfulness) and the level of satisfaction with life (SWL) of patients hospitalized in surgical departments in hospitals in Poland and Ireland. MATERIAL AND METHODS: The research was conducted in a group of 60 surgical patients, including 30 hospitalized in Poland and 30 in Ireland. The tools utilized were the Sense of Coherence Questionnaire for Adults SOC-29 and the Satisfaction with Life Scale (SWLS). Polish versions of both questionnaires were also used. RESULTS: We obtained the following results:- for comprehensibility: in patients undergoing surgery in hospitals in Poland, the mean (M) = 46.3, standard deviation (SD) = 9.8, minimum value (Min) = 28, and maximum value (Max) = 63; in Irish patients, M = 50.8, SD = 9.2,Min = 33, and Max = 71;- for manageability: in patients undergoing surgery in hospitals in Poland, the M = 49.7, SD = 5.07, Min = 37, and Max = 58; in Irish patients, M = 49.3 SD = 6.39, Min = 38, and Max = 63;- for meaningfulness: in patients undergoing surgery in hospitals in Poland, M = 45.5, SD = 4.24, Min = 37, and Max = 54; in Irish patients, M = 44.9 SD = 5.74, Min = 34, and Max = 56. CONCLUSIONS: The results of the study confirmed the assumption that a general SOC correlates with SWL. However, they did not confirm the hypothesis that differences in the strength of patients' SOC, its components and their level of SWL depend on the country of hospitalization.

New therapeutic strategy: Personalization of pancreatic cancer treatment-irreversible electroporation (IRE), electrochemotherapy (ECT) and calcium electroporation (CaEP) - A pilot preclinical study.

In this study, irreversible electroporation (IRE), electrochemotherapy (ECT), and calcium electroporation (CaEP) techniques were investigated as new strategies for human pancreatic cancer. Qualification of the patients, best "therapeutic moment" for each patient, safety, and complications after procedures were examined. In this pilot study were included 13 patients in this study, which were operated on in different pancreatic cancer stages. Patients underwent IRE or ECT with intravenous admission of cisplatin or electroporation with calcium intratumoral administration. The IRE procedure was safe for the patients. Medium overall survival for IRE, IRE + CTH, and IRE + CaCl2 was respectively: 16, 29.5, and 19 months comparing to 10 months in control chemotherapy (CTH) group. Thus, IRE, ECT, and CaEP can be effective strategies for pancreatic cancer treatment.

Assessment of changes in body composition measured with bioelectrical impedance in patients operated for pancreatic, gastric and colorectal cancer.

ntroduction: A proper level of nutrition is significant in the period of convalescence in patients subject to major surgical procedures, particularly due to neoplastic disease. Bioelectrical Impedance Analysis, or BIA is a widely used method in assessing body mass composition. BIA measurement is easy, quick, cheap and repetitive. MATERIAL AND METHODS: We assessed the body composition of 56 patients (25 women and 31 men) hospitalized and operated at the Department of General and Oncological Surgery of the Wroclaw Medical University in the years 2017-2018 using bioelectric impedance. RESULTS: The average body weight loss in the 4th postoperative day was 1.32% of body mass and on the day of release from hospital - 4.23% of body mass in relation to body mass upon admission. The percentage of body fat (FM - Fat Mass) in patients admitted to the department is above the normal range. The change in body composition in hospitalized patients mainly concerns the amount of adipose tissue and the amount of extracellular and intracellular water (ECW - Extracellular Water; ICW - Intracellular Water). CONCLUSIONS: Bioelectrical impedance can be an easy and effective method of assessing body composition and its change in patients undergoing major surgery. Amongst the analyzed groups, patients operated for pancreatic cancer lose the largest percentage of body weight until discharge from the department. Loss of body mass mainly occurs as loss of fat mass (FM).

Pilonidal sinus: finding the righttrack for treatment.

Pilonidal cyst is a troublesome condition affecting usually young people. It significantly influences quality of life and causes low self-esteem. Despite its known pathophysiology and numerous therapeutic methods available, pilonidal cysts still constitute a significant problem in general surgery. A large number of surgical techniques indicates the lack of a single method that ensures therapeutic success, and frequent complications cause both patient's dissatisfaction and frustration of the operator. In many cases, therapy is based on methods developed in a given healthcare center and their efficacy is usually not scientifically verified. Search for optimal strategy is also impeded by lack of an unambiguous clinical classification. In this article, we reviewed publications on various methods of managing pilonidal cyst, and we also presented surgical treatment used in our department. However, we did not manage to point out a surgical method with efficacy high enough to become standard treatment. It indicates the need for further search for new techniques that will give chances for successful treatment of pilonidal cyst.

Intratumoral but not peritumoral lymphatic vessel density measured by D2-40 expression predicts poor outcome in gastric cancer--ROC curve analysis to find cut-off point.

BACKGROUND: Neolymphangiogenesis, a process of lymphatic vessel development in neoplastic tissue, may be a key event in the transmission of cancer cells into lymph nodes. The current study examined the relationship between lymphatic vessel density (LVD) measured by podoplanin (D2-40) expression, clinicopathological parameters and patient survival in gastric cancer. MATERIALS AND METHODS: D2-40 expression was examined by immunohistochemistry in formalin-fixed paraffin-embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40 immunoreactivity was analyzed in intratumoral and peritumoral compartments of tumors and correlated with tumor grade, type in Lauren's classification, lymph node status, distant metastasis, presence of ulceration, inflammatory infiltration, angio-invasion, lymphangio-invasion and patient survival using a Receiver Operating Characteristic (ROC) curve analysis to find cut-off points that enabled fair decision making in survival analysis. RESULTS: The mean values of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced intratumoral LVD measured by D2-40 immunoexpression was correlated with the presence of lymph node metastases (p=0.04). Our study revealed a statistically significant correlation between intratumoral LVD measured by D2-40 expression and survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is significantly correlated with unfavorable prognosis, with a probability of death of approximately 80%. No significant relationship was identified between peritumoral LVD, lymph node status and survival in patients with gastric cancer. CONCLUSION: A high intratumoral LVD measured by D2-40 expression in specimens from primary tumors is strongly associated with lymph node metastasis and predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is a putative predictor of aggressive gastric cancer behavior.

Caspases and their role in gastric cancer.

Caspases (Cysteine Aspartate Specific Proteases) are a group of cysteine-containing proteolytic enzymes produced by the cells of living organisms. They participate in immunological functions, proliferation, cell migration and organization. Caspases also influence the secretion of various regulative factors. Moreover, they are responsible for cellular maturation and reconstruction, and for regulating the number and quality of cells initiating the apoptosis of old cells or those that cannot play their normal role due to abnormalities. Multiple pathological processes are associated with disorders in the activity of caspases. Changes in expression of individual caspases have been observed in gastric cancer. The expression of some caspases is also correlated with particular histological traits and the frequency of metastases, which suggests their possible use as a prognostic factor. It has also been discovered that some somatic mutations in caspase coding genes might lead to inhibition of apoptosis and the progression of the disease. Gene polymorphism may be a gastric cancer risk factor, but may also play a protective function. Considering the less than satisfactory effects of conventional therapeutic methods, the search for alternative ways to activate apoptosis - through gene therapy or selective activation of individual elements of the apoptotic pathways - constitutes a promising direction for studies of new therapeutic strategies. Caspases, enzymes playing a central role in the process of programmed cellular death, may possibly be a key to the development of a more effective anti-cancer therapy.

Control of active B and L cathepsins in tissues of colorectal cancer using cystatins isolated from chicken egg proteins: in vitro studies.

The activity of cysteine peptidases (cathepsins B and L) was estimated in homogenates of tissues sampled during surgery from 60 patients operated due to colorectal tumors. The results were compared to those obtained using tissues in which histopathology disclosed no tumorous cells, obtained from 20 patients of the same group, treated as a control. Activity of the enzymes was inhibited using cysteine peptidase inhibitors isolated from chicken egg proteins. Application of the inhibitors was found to inhibit activity of the enzymes which play a key role in tumor development. It is suggested that in future the inhibitors may provide a component of new generation drugs in the so-called inhibitor therapy.

The evaluation of the influence of a high injury to brachial plexus elements on the condition of neurons of the anterior horns of the spinal cord--experimental research.

The aim of the experimental research was to assess the impact of a high damage to brachial plexus elements on the condition of neurons of spinal cord anterior horns. The research was conducted on 12 rabbits, in which the ventral branches of spinal nerves C5-Th1 were severed. During dissections carried out 7, 30, 60, 180 days after the operation the cervicothoracic segment of the spinal cord was collected. The material was subjected to microscopic histological and ultrastructural examinations, which showed that where brachial plexus elements had been severed some of the neurons of spinal cord anterior horns had died and that the process intensity depended on the time that had passed after the injury.