Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

[Indocyanine green angiography in assessment of parathyroid remnant perfusion after subtotal parathyroidectomy: a case report]. / Angiografiya s indotsianinom zelenym v otsenke perfuzii ostatka tkani parashchitovidnoi zhelezy pri subtotal'noi paratireoidektomii: klinicheskoe nablyudenie.

A 72-year-old female patient with chronic kidney disease stage presented with multiple parathyroid adenomas and tertiary hyperparathyroidism. SPECT/CT with 99mTc-MIBI revealed accumulation of radiopharmaceuticals in 2 out of 4 parathyroid glands. Ultrasound established localization of all parathyroid glands. Subtotal parathyroidectomy with excision of 3 glands and resection of half of the fourth gland was performed. Intraoperative indocyanine green angiography was performed to identify all parathyroid glands and remnant perfusion. There was normal parathyroid function after 6 months.

Biological Response of Chinese Hamster B14-150 Cells to Sequential Combined Exposure to Protons and 12C Ions.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.

Effects of Combined Exposure to Carbon Ions and Protons on the Pool of MCF-7 Breast Cancer Stem Cells In Vitro.

We studied the effects of single and combined action of protons and carbon ions 12C6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e. a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control (p<0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

[Indocyanine green in liver tumor resection]. / Primenenie ICG na etapakh planirovaniya i realizatsii rezektsii pecheni po povodu opukholei.

Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.

[Indocyanine green fluorescence angiography in transoral endoscopic thyroidectomy for papillary thyroid cancer]. / Primenenie fluorestsentnoi angiografii s indotsianinom zelenym v transoral'noi endoskopicheskoi tireoidektomii pri papillyarnom rake shchitovidnoi zhelezy.

OBJECTIVE: To evaluate the effectiveness of ICG angiography in patients with papillary thyroid cancer (PTC) undergoing transoral endoscopic thyroidectomy (TOETVA) and selective neck dissection (level VI). MATERIAL AND METHODS: A retrospective analysis included 20 patients with PTC who underwent TOETVA with selective neck dissection (level VI) between September and December 2022. ICG was administered intravenously (5 mg ´ 3 times). We analyzed parathyroid glands by visual examination and ICG angiography. Fluorescence of all glands was assessed. RESULTS: Twenty patients underwent ICG angiography during TOETVA. A total of 68 parathyroid glands were identified. Only 76.5% (52/68) of parathyroid glands were identified at initial visual examination. ICG angiography additionally localized 12 glands that improved detection to 94.1% (64/68). At least one well-vascularized parathyroid gland was demonstrated by ICG angiography in 16 patients. In all these patients, serum parathyroid hormone was normal in 1 and 10 days after surgery. Two out of four patients who failed to identify a well-vascularized parathyroid gland developed transient hypoparathyroidism. There were no intraoperative and postoperative complications associated with ICG angiography. CONCLUSION: ICG angiography was simple, safe and effective for better identification and preservation of parathyroid glands in patients with PTC undergoing TOETVA. This method was valuable for assessing the viability and function of parathyroid glands and predicting postoperative hypocalcemia.

[Isolated endovascular liver chemoperfusion for liver metastases of uveal melanoma]. / Sposob izolirovannoi endovaskulyarnoi khimioperfuzii pecheni pri metastazakh uveal'noi melanomy v pechen'.

Isolated hepatic perfusion is one of the possible approaches for unresectable liver metastases of uveal melanoma. This technique is rare in modern oncology because of extremely difficult technique and high risk of intra- and postoperative complications. Thus, minimizing surgical trauma and increasing safety and reproducibility of this technique are important. There were 36 procedures of isolated «open¼ hepatic perfusion. The authors describe the first experience of endovascular hepatic perfusion. Advantages and clinical prospects of this method are shown.

Effect of Collagen and GelMA on Preservation of the Costal Chondrocytes' Phenotype in a Scaffold in vivo.

The aim of the study was to compare type I collagen-based and methacryloyl gelatin-based (GelMA) hydrogels by their ability to form hyaline cartilage in animals after subcutaneous implantation of scaffolds. Materials and Methods: Chondrocytes were isolated from the costal cartilage of newborn rats using 0.15% collagenase solution in DMEM. The cells was characterized by glycosaminoglycan staining with alcian blue. Chondrocyte scaffolds were obtained from 4% type I porcine atelocollagen and 10% GelMA by micromolding and then implanted subcutaneously into the withers of two groups of Wistar rats. Histological and immunohistochemical studies were performed on days 12 and 26 after implantation. Tissue samples were stained with hematoxylin and eosin, alcian blue; type I and type II collagens were identified by the corresponding antibodies. Results: The implanted scaffolds induced a moderate inflammatory response in both groups when implanted in animals. By day 26 after implantation, both collagen and GelMA had almost completely resorbed. Cartilage tissue formation was observed in both animal groups. The newly formed tissue was stained intensively with alcian blue, and the cells were positive for both types of collagen. Cartilage tissue was formed among muscle fibers. Conclusion: The ability of collagen type I and GelMA hydrogels to form hyaline cartilage in animals after subcutaneous implantation of scaffolds was studied. Both collagen and GelMA contributed to formation of hyaline-like cartilage tissue type in animals, but the chondrocyte phenotype is characterized as mixed. Additional detailed studies of possible mechanisms of chondrogenesis under the influence of each of the hydrogels are needed.

[Isolated liver perfusion with melphalan followed by pembrolizumab therapy for unresectable metastases of uveal melanoma to the liver]. / Sposob izolirovannoi perfuzii pecheni melfalanom s posleduyushchei terapiei pembrolizumabom v lechenii nerezektabel'nykh metastazov uveal'noi melanomy, ogranichennykh pechen'yu.

Uveal melanoma accounts for 80% of all ocular melanomas, and 30-60% of patients have metastases to the liver. A few patients are candidates for liver resection, and this disease is associated with poor prognosis. There are few data on optimal management of metastatic uveal melanoma. Isolated hepatic perfusion is a perspective method for regional treatment of inoperable metastatic liver lesions with uveal melanoma. We present a patient with uveal melanoma who underwent previous enucleation of the eye. Cancer progressed 15 years later as an isolated inoperable metastatic liver lesion. The patient underwent isolated liver perfusion with melphalan, hyperthermia and oxygenation. Subsequently, the patient received systemic therapy with pembrolizumab. Partial response was achieved 1 month after the procedure. There was no progression for 20 months after surgery under systemic therapy with pembrolizumab. Thus, isolated liver chemoperfusion with melphalan is advisable in these patients.

Anti-Tumor Efficacy of Photodynamic Therapy of Solid Tumors in Laboratory Animals with Guanidine and Biguanidine Derivatives of Chlorine e6.

We evaluated antitumor efficacy of photodynamic therapy of murine Ehrlich carcinoma and rat sarcoma M-1 with new photosensitizers 131-N-(4-aminobutyl)amydo chlorine e6 (1), 132-(5-guanidylbutanamido)-chlorine e6 (2), and 132-(5-biguanidylbutanamido)-chlorine e6 (3). The inhibiting effect of the photodynamic therapy was evaluated by the following parameters: tumor growth inhibition, complete regression of the tumors, and absolute growth rate of the tumor nodes in animals with the continued neoplasia growth. The criterion of cure was the absence of tumors up to 90 days after the therapy. It is shown that the studied photosensitizers have high antitumor activity in the photodynamic therapy of the Ehrlich carcinoma and sarcoma M-1.

In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 µM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

Preclinical Study of Therapeutic Efficacy of a New Russian Radiopharmaceutical 177Lu-DOTA-PSMA.

The therapeutic efficacy of a Russian radiopharmaceutical 177Lu-DOTA-PSMA was studied in vivo using male BALB/c nu/nu (nude) mice with prostate carcinoma 22Rv1 xenografts by tumor growth inhibition criterion. The mean tumor volumes in mice treated with 177Lu-DOTA-PSMA were significantly lower than in animals of the control group. There were no significant differences in the values of tumor growth inhibition between the groups of animals receiving 3.7 or 7.4 MBq of 177Lu-DOTA-PSMA.

Effects of Combined Action of Neutron and Proton Radiation on the Pool of Breast Cancer Stem Cells and Expression of Stemness Genes In Vitro.

Radiation response of cancer stem cells was studied in two breast cancer cell lines: luminal A (MCF-7) and triple negative (MDA-MB-231) subtypes. The relative number of CD44+CD24-/low cancer stem cells of the MCF-7 line increased by 1.7 times under the influence of γ-irradiation at a dose of 4 Gy (p=0.047 in comparison with the control). However, no significant changes were found in the relative number of cancer stem cells and the expression level of OCT4, NANOG, and SOX2 genes after neutron, proton beam irradiation or their combined action at a total equieffective dose of 4 Gy in comparison with the control in both cell lines. The absolute number of cancer stem cells decreased under the influence of neutron or proton radiation in comparison with the control (p<0.05 for both cell lines). At the same time, the effects of sequential exposures to neutron and proton radiation on the size of the cancer stem cell pool depended on the molecular subtype of cancer cells. Additive interaction was observed for MCF-7 line and antagonistic one for MDA-MB-231 line (coefficients of synergism were 0.96 and 0.45, respectively).

Post-Irradiation Recovery of B14-150 Fibrosarcoma Cells after Combined Irradiation with Low and High Linear Energy Transfer.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/µm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/µm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET.

[Vertical resections for larynx cancer with preservation of the thyroid cartridge plates]. / Vertikal'nye rezektsii pri rake gortani s sokhraneniem plastin shchitovidnogo khryashcha.

This article presents a method of organ-preserving surgical treatment of laryngeal cancer, which has been developed and used since 1991 at the Tsyba Medical Radiological Research Center, Branch of the National Medical Research Center of Radiology of the Ministry of Health of Russia. The indications for this method are tumors affecting the middle part of the larynx, limiting its mobility, extending to the anterior commissure, laryngeal ventricle, vestibular fold, lower larynx and one arytenoid cartilage, but retaining mobility in the scooper-cricoid articulation. OBJECTIVE: To increase the functional safety of the larynx and improve the quality of life of patients with laryngeal cancer by using the developed method of organ-preserving surgical intervention in combined treatment. MATERIAL AND METHODS: The study included 197 patients who were operated on by the same method for a primary tumor or in connection with a relapse of the disease. At the first stage, all primary patients underwent a course of radiation or chemoradiation therapy 40-50 Gy. In 78 patients with recurrent laryngeal cancer who underwent resection of the larynx, the previous treatment was carried out in the form of a full course of radiation or chemoradiation therapy with a above 60 Gy. RESULTS: Wound healing by primary intention in patients with preoperative irradiation was observed in 92.4% of cases. With resections for a primary tumor, restoration of functions was observed in 115 (96.6%) patients, and with resections of recurrent tumors - in 71 (91%) patients. Three-year disease-free survival in these patients was 74.4%. CONCLUSION: The presented data showed the high efficiency of the method. This is evidenced by the course of the postoperative period, functional and oncological results are comparable, and in some cases exceed those of other researchers.

Dose Field Shaping and Biological Effectiveness of the Effect of Pulsed Electron Accelerator Novac-11 on Mammalian Cells.

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable.

Yersinia pestis Surface Antigens in Reception of Specific Bacteriophages.

The significance of Yersinia pestis surface antigens in adhesiveness to specific bacteriophages has been studied with the use of two methodological approaches. It was shown that Ail protein immobilized on the surface of polystyrene microspheres (but not in the solution), can bind both the Pokrovskaya phage and pseudotuberculous diagnostic phage. YapF autotransporter interacted with both phages in a water-soluble form, but YapF bound to polystyrene microspheres interacted only with the Pokrovskaya phage. An assumption was made that Ail and YapF proteins can be the primary receptors providing non-specific reversible binding to the phages used in this work.

[Experimental foundation of the use of prolene implant while performing kidney resection].

AIM: To study the method of performing a kidney resection using a prolene mesh implant of medium rigidity and to substantiate the possibility of further application of this method of kidney resection in clinical practice in an experiment. Materials and research methods. The study is experimental. The study was carried out using pig models. In total 50 laboratory animals were included in the study. The operation of kidney resection was simulated using laboratory animals. In 25 cases, the kidney resection was performed according to the classical method, in other 25 cases, the kidney resection was performed according to the authors method of kidney resection using a prolene mesh implant. We studied the average time of surgery, the average weight of the postoperative scar, the pathological presentation of the area of kidney resection at various term after the operation. RESULTS: The average operation time was on average 3.1 minutes (5.7%) longer in the group of laboratory animals operated on with the use of a prolene mesh implant. The average weight of the postoperative scar zone is 1.7 grams (27%) higher in the group of laboratory animals operated on according to the classical hemostasis method of the renal resection area. Interpretation of the results of a histopathological study of the kidney resection area indicates the development of a taft connective tissue structure around the prolene implant of the "patch" type in the shape of strands of dense granulation tissue surrounded by foreign body granulomas. CONCLUSION: The use of a prolene implant when performing a kidney resection is a reliable method of hemostasis of the postoperative defect area, that gives a possibility to minimize cicatricial changes in the renal parenchyma without significant prolongation of the operation time.

Challenges Faced by Clinicians in the Personalized Treatment Planning: A Literature Review and the First Results of the Russian National Cancer Program.

Advances in cancer molecular profiling have enabled the development of more effective approaches to the diagnosis and personalized treatment of tumors. However, treatment planning has become more labor intensive, requiring hours or even days of clinician effort to optimize an individual patient case in a trial-and-error manner. Lessons learned from the world cancer programs provide insights into ways to develop approaches for the treatment strategy definition which can be introduced into clinical practice. This article highlights the variety of breakthroughs in patients' cancer treatment and some challenges that this field faces now in Russia. In this report, we consider the key characteristics for planning an optimal clinical treatment regimen and which should be included in the algorithm of clinical decision support systems. We discuss the perspectives of implementing artificial intelligence-based systems in cancer treatment planning in Russia.

Photodynamic Therapy of Melanoma B16 with Chlorin E6 Conjugated with a PSMA-Ligand.

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.