[Status epilepticus after brain tumor surgery]. / Epilepticheskii status posle udaleniya opukholei golovnogo mozga.

BACKGROUND: Status epilepticus (SE) is characterized by continuous course of clinical and/or electrographic epileptic seizures. There are little data on the course and outcomes of SE after resection of brain tumors. OBJECTIVE: To analyze clinical and electrographic manifestations of SE, its course and outcomes in short-term period after resection of brain tumors. MATERIAL AND METHODS: We analyzed medical records of 18 patients over 18 years old between 2012 and 2019. All patients underwent resection of brain tumor and developed SE after surgery. Clinical criteria were repeated epileptic seizures without interictal recovery of consciousness, stereotypical motor phenomena, impaired consciousness with continued epileptic activity according to video-EEG data. We analyzed EEG data, neurological status, CT and laboratory data. RESULTS: Metastases (33%) and meningiomas (16%) prevailed. Supratentorial tumors were observed in 61% of patients. Two patients had preoperative seizures. Non-convulsive SE was diagnosed in 62% of patients. SE was successfully treated in 77% of cases. Mortality rate in patients with SE was 44%. CONCLUSION: Early postoperative SE is rare after brain tumor surgery (about 0.09%). Nevertheless, this complication is associated with high mortality. Non-convulsive SE is common (62%) that should be considered in postoperative management.

[One-stage reconstructive jejunogastroplasty after previous multiple abdominal surgeries for left-sided diaphragm rupture complicated by gastric incarceration and necrosis]. / Odnomomentnaya rekonstruktivnaya eyunogastroplastika u bol'nogo posle mnozhestvennykh operatsii na bryushnoi polosti po povodu razryva levogo kupola diafragmy s ushchemleniem i nekrozom zheludka.

Acute gastric necrosis is a rare event requiring organ resection. Delayed reconstruction is advisable in patients with peritonitis and sepsis. The most common complication of gastrectomy with reconstruction is failure of esophagojejunostomy and duodenal stump. In case of severe esophagojejunostomy failure, appropriate surgical approach and timing of reconstructive stage should be analyzed. We report one-stage reconstructive surgery in a patient with multiple fistulas after previous gastrectomy. Surgery included reconstructive jejunogastroplasty with jejunal graft interposition. The patient underwent previous several unsuccessful reconstructive procedures complicated by failure of esophagojejunostomy and duodenal stump with external intestinal, duodenal and esophageal fistulas. Nutritional insufficiency, water and electrolyte disorders due to significant loss of proteins and intestinal juice through the drain tubes deteriorated clinical status. Surgical procedures finished reconstruction, provided closure of multiple fistulas and stomas and restored physiological duodenal passage.

[Early predictive biomarkers of posttraumatic epilepsy]. / Rannie prediktivnye biomarkery posttravmaticheskoi epilepsii.

Traumatic brain injury (TBI) affects about 50 million people in the world every year. Posttraumatic epilepsy (PTE) is a significant complication of TBI of any severity. PTE occurs in 20% of patients with TBI. Treatment of patients with PTE is particularly difficult due to obvious tendency towards drug resistance. Currently, there are no validated predictive biomarkers for PTE. Development of a system of validated predictive markers would improve PTE prediction quality and therapeutic approach for these patients. This review is devoted to the current data on the most perspective predictive biomarkers of PTE for clinical practice.

[Pupillometry as a method for monitoring of pupillary light reflex in ICU patients]. / Pupillometriya kak metod monitoringa fotoreaktsii v neiroreanimatsii.

This review is devoted to the modern method of monitoring of pupil diameter and reactivity in patients with acute brain injury. The authors present complete data on diagnostic and prognostic capabilities of automated infrared pupillometry, which should take its rightful place in comprehensive assessment of functional brain state in ICU patients. In authors' opinion, clinical introduction of pupillometry will improve prediction of outcomes following acute brain injury and quality of neurological monitoring in patients with cerebral edema and intracranial hypertension.

Effect of red seaweed sulfated galactans on initial steps of complement activation in vitro.

The research described here presents data on the effect of galactans of red algae, carrageenans (λ/µ/ν-, κ-, κ/ß-, and ι/κ-types), and agar on complement system activation in normal human serum. The experiments were based on well surfaces coated with triggering agents for binding initiating complement components -C3 and C4. The sulfated galactans inhibited C3 binding to lipopolysaccharide with direct dependence on the sulfation degree of polysaccharides. Sulfation degree was also important in carrageenans' capacity to reduce C4 binding to mannan. However, C4 binding to antibodies was considerably activated by carrageenans, especially with 3,6-anhydrogalactose. The gelling carrageenans were able to block antigen binding centers of total serum IgM and with more intensity than non-gelling. No structural characteristics mattered in ameliorating C5 cleavage by plasmin in extrinsic protease complement activation, but λ/µ/ν- and κ/ß-carrageenans almost completely inhibited C5 cleavage. Thus, galactans participated in cell surface biology by imitating surface glycans in inhibition of C3 binding and mannose binding lectin, but as to the tthe heclassical pathway these substances stimulated complement, probably due to their structure based on carrabiose.

[The Influence of A/G Composition of 3' Stop Codon Contexts on Translation Termination Efficiency in Eukaryotes].

Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don't explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA-for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency.

[Convulsive syndrome as a manifestation of acute cerebral damage due to paradoxical air embolism in neurosurgical patients. Series of clinical cases and literature review]. / Sudorozhnyi sindrom kak proyavlenie ostrogo tserebral'nogo povrezhdeniya, obuslovlennogo paradoksal'noi vozdushnoi emboliei u neirokhirurgicheskikh bol'nykh. Seriya klinicheskikh nablyudenii i obzor literatury.

INTRODUCTION: Paradoxical air embolism (PAE) is a rare potentially fatal complication followed by entering of air emboli from the right cardiac chambers and pulmonary artery to large circulation circle. OBJECTIVE: To analyze five patients who underwent neurosurgical intervention complicated by PAE and early postoperative convulsive syndrome. MATERIAL AND METHODS: There were five patients who developed early postoperative convulsive syndrome after previous neurosurgery in sitting position complicated by PAE. Convulsive syndrome required intensive care at the ICU. MRI confirmed ischemic foci de novo outside the zone of surgical intervention in all cases. All patients underwent video-EEG monitoring in order to select anticonvulsant therapy and evaluate its effectiveness. The authors were able to match the epileptogenic focus in the cerebral cortex with MRI data. Available literature data devoted to the problem of convulsive syndrome after neurosurgery complicated by PAE were analyzed. RESULTS: The focus of epileptiform activity coincided with one of the foci of hyperintense MR signal in all cases. CONCLUSION: Video-EEG monitoring is advisable in patients with impaired consciousness who underwent neurosurgery complicated by PAE.

Effect of carrageenans on some lipid metabolism components in vitro.

The research described here focused on the effect of sulfated red algal polysaccharides (κ-, κ/ß-, ι/κ-carrageenan) individually and in combination with lipopolysaccharide (LPS) on the synthesis of prostaglandin E2 (PGE2) and cytokines (interleukin [IL]-1ß and IL-6) in whole blood model in vitro. The results demonstrated that, at high concentrations, carrageenans have substantial ability to modulate PGE2 synthesis and stimulate IL-1ß and IL-6 synthesis. A low degree of sulfate and high molecular weight were a prerequisite for the ability of carrageenans to modulate PGE2 synthesis. Further, we investigated the ability of the carrageenans alone and in combination with casein to affect bile salt permeability through an artificial membrane imitating the gastrointestinal barrier. The least sulfated κ/ß-carrageenan could retain bile salt permeation the most but less efficiently than cholestyramine. The polysaccharides did not affect pancreatic lipase activity. Our data confirm a possible mechanism of the cholesterol-reducing properties of carrageenan.

Model of Ovarian Adenocarcinoma Spheroids for Assessing Photodynamic Cytotoxicity.

The aim of the study was to compare the relevance of ovarian adenocarcinoma spheroids with that of a monolayer culture for assessing photodynamic effect of the tetrakis(4-benzyloxyphenyl)tetracyanoporphyrazine photosensitizer. MATERIALS AND METHODS: The work was performed on SKOV-3 human ovary adenocarcinoma cells grown in vitro in a monolayer culture and in the form of tumor spheroids obtained using culture plates with ultra-low attachment. We determined the photoinduced toxicity of porphyrazine on a monolayer culture using the MTT assay; the effect on the spheroids was tested by assessing the dynamics of their growth. Cellular uptake of porphyrazine was analyzed by confocal microscopy. RESULTS: Porphyrazine has a pronounced photodynamic effect on SKOV-3 cells. When exposed to light at a dose of 20 J/cm2, the IC50 value 24 h after exposure was 2.3 µM for SKOV-3 monolayer culture. For the spheroids, the effect manifested after a latency period: significant growth retardation of the treated spheroids appeared no sooner than 5 and 9 days after exposure. Notably, no decrease in the initial size of the treated spheroids was observed under any of the photodynamic regimes. The penetration depth of porphyrazine into spheroids was 50-100 µm during 24 h incubation. CONCLUSION: The limited penetration of the photosensitizer into the body of spheroids and its predominant accumulation in the surface layers can be one of the key factors behind the significant differences in the photodynamic response between the surface and deep layers of a spheroid. For cells located close to the spheroid surface, the photodynamic effect is comparable to that for a monolayer culture, while in deeper layers, the cells remain viable and support/maintain the growth of the spheroid even under intense photo-exposure. The fact that the in vitro distribution is similar to the inhomogeneous accumulation of photosensitizers in tumors in vivo allows us to consider spheroids more relevant than a monolayer culture for studying photodynamic anti-tumor effects.

[Promising races of baker's yeast for the production of food ingredients enriched with selenium and chromium].

It is known, that Saccharomycetes can accumulate mineral substances with targeted enrichment of the growth medium. However, the influence of the genetic affiliation of the culture and the technological factors of yeast strains, the composition of growth media on the efficiency of essential trace elements incorporation into the biomass and on the change of theirs intracellular components content have hardly been investigated. In this regard, the aims of this work was to select promising races of yeast Saccharomyces cerevisiae, develop a biotechnological method for obtaining food ingredients enriched with selenium and chromium on their basis, and study their trace element composition. Material and methods. Industrial strains of baker's yeast (Saccharomyces cerevisiae) were used: RCAM 01137, Y-3439 and Y-581. Yeast were grown on malt wort (pH 4.6) with a dry matter content of 12% with the addition of mineral salts in stationary conditions at a temperature of 30 °C for 18 h, after which the yeast biomass was separated by centrifugation. A method for enriching yeast with trace elements has been selected, which consists in the process of culturing cells on malt growth media containing chromium chloride or selenium dioxide in various concentrations. The total protein content was determined by the Kjeldahl method, polysaccharides and ergosterol - by spectrofluorometric method, selenium - by fluorimetric method. The content of trace elements in yeast biomass enriched with chromium was studied by mass spectrometric method with inductively coupled plasma. Results. It was shown that the highest specific growth rate was demonstrated by the yeast strains RCAM 01137 and Y-3439, and the highest level of maltase activity was in the Y-581 strain. It was found that the amount of biomass after cultivation of the yeast S. cerevisiae RCAM 01137 and Y-3439 was 6.00 и 5.42 g/100 cm3, respectively. It was noted, that the yeast S. cerevisiae Y-581 had capability of high synthesis of ergosterol (1.08±0.04%), the level of which was 2 fold higher than other strains. S. cerevisiae RCAM 01137 yeast showed the greatest ability to selenium enrichment, its content in biomass increased 137 fold and amounted to 2740 µg% when cultivated on a medium containing 800 µg/dm3. S. cerevisiae Y-581 yeast strain showed the highest capability to chromium sorption. The chromium concentration in its biomass was 8340 µg% in case of cultivating on a medium containing 750 µg/dm3. The usage of about 2.7 g of selenium enriched yeast biomass, or 1.0 g chromium enriched one, satisfies the daily requirement for these trace elements. Conclusion. Cultivation of S. cerevisiae cells on growth media containing trace elements makes it possible to obtain yeast biomass samples that can be used to obtain food ingredients for creating food products that contribute to the maintaining human health and improve the quality and duration of life.

Role of conduct problems in the relation between Attention-Deficit Hyperactivity disorder, substance use, and gaming.

Known comorbidities for Attention-Deficit Hyperactivity Disorder (ADHD) include conduct problems, substance use disorder and gaming. Comorbidity with conduct problems may increase the risk for substance use disorder and gaming in individuals with ADHD. The aim of the study was to build a causal model of the relationships between ADHD and comorbid conduct problems, and alcohol, nicotine, and other substance use, and gaming habits, while accounting for age and sex. We used a state-of-the-art causal discovery algorithm to analyze a case-only sample of 362 ADHD-diagnosed individuals in the ages 12-24 years. We found that conduct problem severity mediates between ADHD severity and nicotine use, but not with more severe alcohol or substance use. More severe ADHD-inattentive symptoms lead to more severe gaming habits. Furthermore, our model suggests that ADHD severity has no influence on severity of alcohol or other drug use. Our findings suggest that ADHD severity is a risk factor for nicotine use, and that this effect is fully mediated by conduct problem severity. Finally, ADHD-inattentive severity was a risk factor for gaming, suggesting that gaming dependence has a different causal pathway than substance dependence and should be treated differently. By identifying these intervention points, our model can aid both researchers and clinicians.

Potential infection of grazing cattle via contaminated water: a theoretical modelling approach.

Wastewater discharge and agricultural activities may pose microbial risks to natural water sources. The impact of different sources can be assessed by water quality modelling. The aim of this study was to use hydrological and hydrodynamic models to illustrate the risk of exposing grazing animals to faecal pollutants in natural water sources, using three zoonotic faecal pathogens as model microbes and fictitious pastures in Sweden as examples. Microbial contamination by manure from fertilisation and grazing was modelled by use of a hydrological model (HYPE) and a hydrodynamic model (MIKE 3 FM), and microbial contamination from human wastewater was modelled by application of both models in a backwards process. The faecal pathogens Salmonella spp., verotoxin-producing Escherichia coli O157:H7 (VTEC) and Cryptosporidium parvum were chosen as model organisms. The pathogen loads on arable land and pastures were estimated based on pathogen concentration in cattle faeces, herd prevalence and within-herd prevalence. Contamination from human wastewater discharge was simulated by estimating the number of pathogens required from a fictitious wastewater discharge to reach a concentration high enough to cause infection in cattle using the points on the fictitious pastures as their primary source of drinking water. In the scenarios for pathogens from animal sources, none of the simulated concentrations of salmonella exceeded the concentrations needed to infect adult cattle. For VTEC, most of the simulated concentrations exceeded the concentration needed to infect calves. For C. parvum, all the simulated concentrations exceeded the concentration needed to infect calves. The pathogen loads needed at the release points for human wastewater to achieve infectious doses for cattle were mostly above the potential loads of salmonella and VTEC estimated to be present in a 24-h overflow from a medium-size Swedish wastewater treatment plant, while the required pathogen loads of C. parvum at the release points were below the potential loads of C. parvum in a 24-h wastewater overflow. Most estimates in this study assume a worst-case scenario. Controlling zoonotic infections at herd level prevents environmental contamination and subsequent human exposure. The potential for infection of grazing animals with faecal pathogens has implications for keeping animals on pastures with access to natural water sources. As the infectious dose for most pathogens is more easily reached for calves than for adult animals, and young calves are also the main shedders of C. parvum, keeping young calves on pastures adjacent to natural water sources is best avoided.

[A favorable outcome of surgical treatment and intensive care in a child admitted in a severe condition in the setting of aneurysmal subarachnoid hemorrhage (a clinical case and literature review)]. / Blagopriiatnyi iskhod khirurgicheskogo lecheniia i intensivnoi terapii u rebenka, postupivshego v tiazhelom sostoianii na fone anevrizmaticheskogo subarakhnoidal'nogo krovoizliianiia (klinicheskoe nabliudenie i obzor literatury).

Treatment of children in the acute stage of hemorrhage from cerebral aneurysms is based on clinical cases reported in the literature and descriptions of small series of observations. There are no studies that enable the development of evidence-based approaches to intensive care in treatment of children with aSAH. We present a clinical case with a favorable outcome of complex treatment in a child admitted to the Burdenko Neurosurgical Institute at an extremely severe condition. The efficacy of treatment was based on a timely urgent neurosurgical intervention and adequate intensive therapy in the form of extended neuromonitoring with continuous measurement of intracranial pressure, which enabled using the whole complex of measures for timely management of intracranial hypertension. A favorable outcome (a GOS score IV) after this severe aneurysmal SAH indicates that there are no absolute contraindications for neurosurgical treatment of children with cerebral aneurysms.

[Biodegradation of proteins of grain raw materials for the production of new bakery products].

The effect of enzyme systems on the degree of protein destruction of grain crops to obtain new types of bakery products has been studied. Protein and amino acid composition of triticale grain crop in comparison with wheat and rye one has been studied. The high biological value of triticale proteins containing 38.75% of essential amino acids while in wheat - 34.93% has been shown. The influence of different enzyme systems (ES) with proteolytic action on the efficiency of catalytic modification of triticale proteins has been investigated. It was found that the highest activity was shown by the enzymatic system ES-1, synthesized by the mycelial fungus Aspergillus oryzae, as a result of which at a concentration of 5 u/g, the level of accumulation of amine nitrogen in triticale enzymatic hydrolysates was 125 mg%; the degree of hydrolysis of proteins was 90%. Enzyme preparations of bacterial origin, as well as alkalase and papain had a lower ability to hydrolyze triticale proteins. The fractional composition of modified proteins obtained by ES-1 showed a decrease in their molecular weight (to 35 kDa). Analysis of amino acid composition in grain enzymatic hydrolysates showed that as a result of exposure to FS-1, about 50% of the total number of amino acids passed into the free state, of which 38.8 to 43.6% were essential amino acids. The recipes of breads, containing composition of wheat flour and fermentolizates of the whole-grain triticale flour in the ratio 1:1 have been tested. The amino acid composition of the bread showed that the test samples contained 6.2 fold more free amino acids than the control. The use of fermented triticale in the recipes of bread allowed to increase the content of essential amino acids such as methionine, valine, isoleucine, leucine, phenylalanine, threonine, tryptophan and lysine in 2.0-5.0 times. It was shown that the developed technology allowed baking bread containing peptides with reduced molecular weight and free amino acids, which by its organoleptic and physic-chemical parameters corresponded to classic bakery products.

The Effect of the Targeted Recombinant Toxin DARPin-PE40 on the Dynamics of HER2-Positive Tumor Growth.

The development of targeted toxins based on non-immunoglobulin targeting molecules appears to be one of the most advanced approaches in the targeted therapy of malignant tumors with a high expression of the HER2 receptor. Earlier, we showed that the targeted toxin DARPin-PE40 consisting of the HER2-specific non-immunoglobulin polypeptide (the targeting module) and a fragment of Pseudomonas exotoxin A (the toxic module) exhibits an antitumor effect in vivo against the HER2-positive adenocarcinoma xenograft. In this work, an in-depth analysis of the effect of DARPin-PE40 on the growth dynamics of experimental xenograft tumors was carried out. DARPin-PE40 was shown to inhibit tumor growth at a dose of 25 and 50 µg/animal and to cause tumor node reduction at a dose of 80 µg/animal, followed by growth resumption at the end of therapy. An evaluation of the tumor growth dynamics revealed statistically significant differences in tumor volume in mice in the experimental groups compared to the control group. The results testify to the potential of using the created targeted toxin as an agent for the targeted therapy of HER2-overexpressing tumors.

[The management of patients with new epileptic seizures in the early period after resection of hemispheric tumors: two case reports and a literature review]. / Taktika vedeniia patsientov s vpervye épilepticheskimi pristupami v rannem periode posle udaleniia opukholei bol'shikh polusharii: dva nabliudeniia i obzor literatury.

Epileptic seizures developing for the first time after a neurosurgical intervention (de novo seizures) are a challenge for choosing an optimal treatment. The pathogenesis of these seizures is often associated with factors that become inactive in the early postoperative period. These seizures can not serve the basis for diagnosing symptomatic epilepsy and should be regarded as a brain response to surgery, and patients do not need anticonvulsant therapy that reduces the quality of life. But in some situations, new early postoperative seizures serve the onset of symptomatic epilepsy and require prolonged anticonvulsant therapy. To date, one of the main techniques to identify the nature of newly developed seizure and to plan further treatment (whether or not to use anticonvulsant therapy) is video EEG monitoring. We present two clinical cases of patients who developed de novo convulsive seizures in the early postoperative period in similar situations after resection of intracerebral tumors. The use of video EEG monitoring allowed avoiding unreasonable use of anticonvulsant therapy in one of the patients.

Population specific analysis of Yakut exomes.

We studied the genetic diversity of the Yakut population using exome sequencing. We performed comparative analysis of the Yakut population and the populations that are included in the "1000 Genomes" project and we identified the alleles specific to the Yakut population. We showed, that the Yakuts population is a separate cluster between Europeans and East Asians.

[The association of the FAS/APO-1 (rs2234767) gene polymorphism with the risk and rapid progression of multiple sclerosis]. / Assotsiatsiia polimorfizma gena FAS/APO-1 (rs2234767) s riskom razvitiia i bystrogo progressirovaniia rasseiannogo skleroza.

AIM: To evaluate the association of the FAS/APO-1 (rs2234767) gene polymorphism with the risk of multiple sclerosis and its progression dynamics. MATERIAL AND METHODS: A case-control study included 100 patients with recurrent multiple sclerosis (MS), Russians from the Altai Territory, and 100 healthy volunteers. Real-time polymerase chain reaction was used to genotype the 1377G>A polymorphism in the promoter of the FAS/APO-1 (rs2234767) gene. Association of this polymorphism with the risk of multiple sclerosis and its progression was evaluated. RESULTS: The G/А genotype and the А-allele were associated with the increased risk of multiple sclerosis. The G/А genotype and the А-allele were associated with the risk of high progression rate of the disease. The G/G genotype and the G-allele had a protective effect. CONCLUSION: Predisposition to MS as well as to high progression rate are associated with the FAS/APO-1*G/А gene in Russians living in the Altai Territory. Further research is required to make the conclusion.

Effect of carrageenans alone and in combination with casein or lipopolysaccharide on human epithelial intestinal HT-29 cells.

The research described here was focused on the effect on human intestinal epithelial cell monolayers of sulfated red algal polysaccharides (κ-, λ-, and κ/ß-carrageenans) alone and in combination with casein or lipopolysaccharide (LPS). HT-29 cells were investigated under normal and stress conditions; stress was induced by exposure to ethanol. Cell viability was monitored with a real-time system. The change in binding properties of negatively sulfated red algal polysaccharides assessed by the measurement of free carrageenans in mixtures with casein or McCoy's 5 A culture medium by means of toluidine blue O. Low sulfate content and the presence of 3,6-anhydogalactose are prerequisites for the recovery of ethanol-exposed HT-29 cells by carrageenans. Analysis of carrageenan binding ability confirmed that casein and LPS should affect carrageenan activity. Whether the combined action of the mucin-containing layer and carrageenans or the action of carrageenans alone was responsible for enhanced cell viability under stress conditions induced by ethanol is a subject for further research. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2843-2850, 2017.

Spheroids of HER2-Positive Breast Adenocarcinoma for Studying Anticancer Immunotoxins In Vitro.

Tumor response to therapeutic treatment is largely determined by its heterogeneity and the presence of intercellular junctions, hindering the penetration of large molecules deep into the three-dimensional structure of the tumor. In that context, 3D in vitro tumor models such as cancer cell spheroids are becoming increasingly popular. We obtained spheroids of human breast adenocarcinoma SKBR-3 overexpressing the HER2 cancer marker. The toxicity of HER2-targeted immunotoxin 4D5scFv-PE40 against spheroids was shown to be several orders of magnitude lower compared to a monolayer cell culture. The significant difference in the severity of the immunotoxin effect can be explained by the fact that it ineffectively penetrates the spheroid and predominantly influences the cells of the outer layers. The resulting tumor spheroid model can be used in development of drugs for targeted therapy as well as to study ways to improve the efficiency of anticancer agents by targeting cell-cell contacts.