Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma.

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).

Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML.

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration.

Spatial characterization of light beams analyzed by cylindrical-grating slit-less spectrometers.

In this work, we theoretically analyze the spatial information provided by cylindrical-grating slit-less spectrometers. We raise attention on the often not considered property that the spatial features acquired using these spectrometers are different from what can be obtained using a spectrometer with an entrance slit. In relation to this, we also highlight that they do not provide information directly on the real spatial beam profile. It is important to consider this fact in spatio-spectral analysis of extreme ultraviolet radiation, often carried out using cylindrical-grating slit-less spectrometers. Since the models used are based on the Fresnel diffraction integral and ideal optical systems, the results are valid also for other spectral regions.

What contributes to long-term quality of life in breast cancer patients who are undergoing surgery? Results of a multidimensional study.

PURPOSE: This study aims to examine the key determinants of long-term quality of life in breast cancer patients who are undergoing surgery using a multidimensional approach and taking into account preoperative and post-operative psychological characteristics such as anxiety, depression, posttraumatic growth, body image, and physical activity as well as medical parameters. METHODS: The study involved 63 breast cancer patients from the Department of Surgery at the University of Szeged. Assessments occurred 1 day before surgery as well as 3 days and 18 months after surgery using the Spielberger State and Trait Anxiety Inventory (STAI), Beck's Depression Inventory (BDI), Functional Assessment of Cancer Therapy-Breast Cancer Scale (FACT-B), Posttraumatic Growth Inventory (PTGI) and Breast Impact of Treatment Scale (BITS). Data relating to physical activity, medical parameters and sociodemographic characteristics were also collected. RESULTS: The level of depression did not change over time. State anxiety decreased 18 months after the surgery compared to before the surgery; however, there was a greater decrease immediately after the surgery and then anxiety increased again 18 months later. Trait anxiety was associated with quality of life, posttraumatic growth and body image. Posttraumatic growth and the level of depression were found to be possible contributing factors to the increase in long-term quality of life. CONCLUSIONS: The results show that the timely detection and proper management of psychological distress and the enhancement of posttraumatic growth are of great value, as they might be important contributing factors to long-term quality of life in breast cancer patients.

Carrier-envelope phase changes in the focal region: propagation effects measured by spectral interferometry.

Spectral interferometric measurements are presented that show how wave propagation affects the carrier-envelope phase (CEP) of an ultrashort pulse in the focal region and results in variations that are different from the Gouy phase shift. Wavelength-dependent properties of the input beam are investigated and are seen to influence how the CEP is altered. The measured CEP changes show characteristics similar to the variations predicted by theory.

First Hungarian case of an infection caused by multidrug-resistant Bacteroides fragilis strain.

We report a case caused by a multidrug-resistant (MDR) Bacteroides fragilis strain isolated from abdominal fluid of a male patient with complex underlying diseases. The patient had received antibiotics prior to the presented case. As far as we know, this case with a MDR B. fragilis is the first from Hungary, and Eastern-Europe, as well.

[HEALTH INSURANCE ASPECTS OF PHYSIOTHERAPEUTIC CARE OF NEUROLOGY DISORDERS IN OUTPATIENT CARE]. / A NEUROLÓGIAI KÓRKÉPEK FIZIOTERÁPIÁS ELLÁTÁSÁNAK EGÉSZSÉGBIZTOSÍTÁSI VONATKOZÁSAI A JÁRÓBETEG-SZAKELLÁTÁSBAN.

BACKGROUND AND PURPOSE: The aim of our study is to analyse the ambulatory rehabilitation care of patients with neurological disorders in the field of physiotherapy. METHODS: Data derive from the database of the Hungarian National Health Insurance Fund Administration (year 2009). The analyses covered patients with diagnosis "G00-G99 Diseases of the nervous system" according to the International Classification of Diseases and underwent physiotherapy treatment. RESULTS: In 2009 altogether 190986 patients with neurological disorders received physiotherapy treatment in outpatient care, representing 1331675 cases and got 388.215 million Hungarian Forint health insurance reimbursement. The number of patients with nerve, nerve root and plexus disorders was 39 patients/10 000 population for males and 66 patients/10000 population for females. The number of patients with cerebral palsy and other paralytic syndromes was 49 patients/10000 population for males and 35 patients/10000 population for females. The number of patients with episodic and paroxysmal disorders was 33 patients/10000 population for males and 52 patients/10000 population for females. CONCLUSION: In the outpatient physiotherapy care the utilization indicators for female patients were higher in nerve, nerve root and plexus disorders and episodic and paroxysmal disorders, while in cerebral palsy and other paralytic syndromes the utilization by male patients was higher. There are important age and gender inequalities in the utilization of physiotherapy care of patients with neurological disorders.

Rotation of the polarization direction and reversal of helicity of ultrashort pulsed beams propagating in free space.

We unveil the origin of the recently revealed polarization-state changes of polarization-shaped few-cycle pulses induced by free-space beam propagation. Simple rules are formulated to show how the orientation and ellipticity of the instantaneous polarization ellipse of the source and propagated pulses relate to each other. We demonstrate our findings with examples that clearly display the relationships found and highlight their relevance. We show, for example, that pulses often used in high-harmonic generation or attosecond pulse production rotate as a whole during free-space beam propagation or upon focusing. A pulse that may reverse its ellipticity from right-handed to left-handed during propagation is also introduced. It is shown that these effects are independent of the beam size and/or focal length. We also present how these instantaneous polarization-state changes could be noticed in classical measurements of light polarization using polarizers, phase retarders, and time-integrating detectors.

[Analysis of health insurance data on home nursing care in Hungary]. / Az otthoni szakápolás egészségbiztosítási vonatkozásainak elemzése Magyarországon.

INTRODUCTION: Home nursing care was introduced in Hungary in 1996. AIM: The aim of this study was to analyse health insurance data and utilization indicators of the Hungarian home nursing care. METHOD: Data derived from the database of the National Health Insurance Fund Administration (2001-2012). The number of patients and visits, and the ratio of special nursing and special therapy (physiotherapy, speech therapy) were analysed. RESULTS: The number of patients increased by 41.3% from 36.560 (2001) to 51.647 (2012). The number of visits also increased by 41.9% from 841.715 (2011) to 1.194.670 (2012). Significant geographical inequalities were found in the ratio of special nursing and special therapy as well as nursing needs. The ratio of reimbursement for special nursing was the highest in county Nógrád (80.4%), Szabolcs-Szatmár-Bereg (79.7%) and Komárom-Esztergom (74.6%), while the lowest in county Zala (53.0%), Csongrád (52.7%) and Budapest (47.9%). CONCLUSIONS: There are significant inequalities in the home nursing care in Hungary. In order to decrease these inequalities, specific guidelines should be developed for home nursing care.

OLD AND NEW NEUROENDOCRINE MOLECULES: SOMATOSTATIN, CYSTEAMINE, PANTETHINE AND KYNURENINE.

The aim of this review is to commemorate Hans Selye, endocrinologist, the most famous researchers of stress and to briefly summarize the major features of somatostatin (SST), cysteamine (CysA) and patethine (PAN) in neuroendocrinological aspect, which are closely related to his scientific work. In addition, some metabolites of kynurenine pathway (KP) were also mentioned in this paper, as new, possible target molecules in neuroendocrinology. R. Guillemin and A. V. Schally were the main pioneers of the discovery of SST in the 1970's. SST primarily is known as an inhibitor of growth hormone secretion and additionally reduces the gastric acid and pepsin release and also the gastroduodenal mucosal blood flow. These effects are very important in the pathophysiology of peptic ulcer bleeding, which is related to the CysA-evoked perforating duodenal ulcer experimental stress model in rats developed by Selye and Szabo. CysA is a naturally occurring duodenal ulcerogen, which depletes SST in the gastric mucosa and certain brain regions. Furthermore, in addition to depleting SST, CysA also causes adrenocortical necrosis, suggesting an interaction between the central/peripheral nervous system and the neuroendocrine system. The antioxidant PAN, formulated besides the CysA, has similar effects: it attenuates the levels of SST and prolactin in the cerebral cortex and hypothalamus through the accumulation of CysA within cells throughout the body. As new perspectives the KP may be involved in the modulation of neuroendrocrine processes: different agonists and antagonists of glutamate receptors regulate the hypothalamic-pituitary-adrenal axis and kynurenic acid augments the anxiolytic stress responses in neonatal chicks. The pro-inflammatory cytokine-induced and the toxic heavy oil contaminations-evoked alterations in the KP indirectly contribute to the development of neuroendocrine disorders. In summary, there have been highly important developments in neuroendocrinology since the early findings of Selye. Although there are as yet relatively few data about the potential role of kynurenines in neuroendocrinology, the results already achieved are extremely noteworthy and immensely promising.

[Comparison of surgical patients with gastroesophageal reflux disease and Barrett's esophagus]. / Refluxbetegség és Barrett-nyelocso miatt mutétre kerülo betegek összehasonlító vizsgálata.

INTRODUCTION: Barrett's esophagus (BE) is the only known precursor of adenocarcinoma occuring in the lower third of the esophagus. According to statistics, severity and elapsed time of gastroesophageal reflux disease (GERD) are major pathogenetic factors in the development of Barrett's esophagus. PATIENTS AND METHODS: In a retrospective study between 2001 and 2008, we compared the preoperative results (signs and sympthoms, 24 hour pH manometry, esophageal manometry, Bilitec) and treatment efficacy of 176 GERD patients and 78 BE patients, who have undergone laparoscopic Nissen procedure for reflux disease. RESULTS: The two groups of patients had similar demographic features, and elapsed time of reflux sympthoms were also equal. Both groups were admitted for surgery after a median time of 1.5 years (19.87 vs. 19.20 months) of ineffective medical (proton pump inhibitors) treatment. Preoperative functional tests showed a more severe presence of acid reflux in the BE group (DeMeester score 18.9 versus 41.9, p < 0.001). On the other hand, mano-metry - despite confirming lower esophageal sphincter (LES) damage - did not show difference between the two groups (12.10 vs. 12.57 mmHg, p = 0.892). We did not experience any mortality cases with laparoscopic antireflux procedures, although in two cases we had to convert during the operation (1 due to extensive adhesions, and 1 due to injury to the spleen). 3 months after the procedure - according to Visick score - both groups experienced a significant decrease, or lapse in reflux complaints (group I: 73%, group II: 81% of patients), LES functions improved (17.58 vs.18.70 mmHg), and the frequency and exposition of acid reflux decreased (DeMeester score 7.73 vs. 12.72). CONCLUSION: The severity of abnormal acid reflux occuring parallel with the incompetent function of the damaged LES triggers not only inflammation in the gastroesophageal junction (GEJ), but also metaplastic process, and the development of Barrett's esophagus. Laparoscopic Nissen procedure for reflux disease can further improve outcome among patients with GERD not responding to conservative therapy.

Quantification of Soluplus for Dissolution Tests: SEC Method Development and Validation.

The quantification of both polymer and drug during the dissolution of an amorphous solid dispersion (ASD) in aqueous media arouses great interest and may aid in the formulation. However, the available quantification methods for polymer excipients are limited, expensive, and challenging compared to drugs. In this work, a size exclusion chromatography method (HPLC-SEC) was developed and validated to determine the concentration of a frequently used polymer excipient, Soluplus® (Sol). In order to develop a method for the quantification of dissolved Soluplus®, two methods (SEC-UV and SEC-RID) with two injection volumes were tested with standard solutions of three different batches of Soluplus. The developed HPLC-SEC-UV method showed acceptable linearity (R2 > 0.9990) for all batches of Soluplus, good accuracies above a concentration of 0.1 mg/mL (coefficient of variation < 2%), relatively good precision at a concentration of 0.1 mg/mL (coefficient of variation < 2.5%), and high recoveries at a concentration of 0.75 mg/mL (coefficient of variation < 0.5%). The presence of Felodipine (Fel) and Lumefantrine (Lum) in the liquid media did not interfere with Soluplus quantification. The use of various surfactants, such as Tween® 80, Tween® 20, Span® 80, Span® 20, Kolliphor® TPGS, and sodium lauryl sulphate at a low concentration (0.005 mg/mL) did not show any effect on Soluplus® and did not interfere with Soluplus® quantification with any of the Soluplus batches. The addition of lithium bromide (LiBr) to the mobile phase within a concentration range of 0.05 to 1.0 M did not improve Soluplus® quantification.

Human electrophysiological and pharmacological properties of XEN-D0101: a novel atrial-selective Kv1.5/IKur inhibitor.

The human electrophysiological and pharmacological properties of XEN-D0101 were evaluated to assess its usefulness for treating atrial fibrillation (AF). XEN-D0101 inhibited Kv1.5 with an IC50 of 241 nM and is selective over non-target cardiac ion channels (IC50 Kv4.3, 4.2 µM; hERG, 13 µM; activated Nav1.5, >100 µM; inactivated Nav1.5, 34 µM; Kir3.1/3.4, 17 µM; Kir2.1, >>100 µM). In atrial myocytes from patients in sinus rhythm (SR) and chronic AF, XEN-D0101 inhibited non-inactivating outward currents (Ilate) with IC50 of 410 and 280 nM, respectively, and peak outward currents (Ipeak) with IC50 of 806 and 240 nM, respectively. Whereas Ilate is mainly composed of IKur, Ipeak consists of IKur and Ito. Therefore, the effects on Ito alone were estimated from a double-pulse protocol where IKur was inactivated (3.5 µM IC50 in SR and 1 µM in AF). Thus, inhibition of Ipeak is because of IKur reduction and not Ito. XEN-D0101 significantly prolonged the atrial action potential duration at 20%, 50%, and 90% of repolarization (AF tissue only) and significantly elevated the atrial action potential plateau phase and increased contractility (SR and AF tissues) while having no effect on human ventricular action potentials. In healthy volunteers, XEN-D0101 did not significantly increase baseline- and placebo-adjusted QTc up to a maximum oral dose of 300 mg. XEN-D0101 is a Kv1.5/IKur inhibitor with an attractive atrial-selective profile.

[Developing FGFR inhibitors as potential anti-cancer agents]. / Potenciális antitumor hatású FGFR inhibitorok fejlesztése.

Fibroblast Growth Factor Receptor (FGFR) family is a sequentially highly related subgroup of membrane proteins consisting of four tyrosine kinase type enzyme: FGFR1, FGFR2, FGFR3 and FGFR4. These are kinases of great interest in a wide spectrum of physiological processes such as tissue repair via controlling cell proliferation. As initiatiors of cell proliferation, in some cases they have leading roles in several types of cancer, eg. breast cancer, pancreas cancer, gastric tumors and multiple myeloma via overexpression and/or mutation. This phenomenon makes them promising targets for drug development in order to develop signal transduction therapies based on small molecule FGFR inhibitors. We have developed two main groups of lead molecules: compounds with benzotiophene and oxindole cores utilizing numerous methods from in silico modelling via in vitro biochemichal assays and testing on relevant cell lines to cytotoxicity assays.

The impact of the first wave of COVID-19 on students' attainment, analysed by IRT modelling method.

Universities around the world were closed for several months to slow down the spread of the COVID-19 pandemic. During this crisis, a tremendous amount of effort was made to use online education to support the teaching and learning process. The COVID-19 pandemic gave us a profound insight into how online education can radically affect students and how students adapt to new challenges. The question is how switching to online education affected dropout? This study shows the results of a research project clarifying the impact of the transition to online courses on dropouts. The data analysed are from a large public university in Europe where online education was introduced in March 2020. This study compares the academic progress of students newly enroled in 2018 and 2019 using IRT modelling. The results show that (1) this period did not contribute significantly to the increase in dropout, and we managed to retain our students.(2) Subjects became more achievable during online education, and students with less ability were also able to pass their exams. (3) Students who participated in online education reported lower average grade points than those who participated in on-campus education. Consequently, on-campus students could win better scholarships because of better grades than students who participated in online education. Analysing students' results could help (1) resolve management issues regarding scholarship problems and (2) administrators develop programmes to increase retention in online education.

Nursing of Pike-Perch (Sander lucioperca) in Recirculating Aquaculture System (RAS) Provides Growth Advantage in Juvenile Growth Phase.

This study aimed to estimate the efficacy of two pike-perch juvenile production technologies: exclusive Recirculating Aquaculture System (RAS) culture (the RAS group) and pond larviculture with a transfer to the RAS at the 42nd day post-hatch (DPH). Both direct weaning on dry feed (the Pond-D group) and 10-day gradual weaning using bloodworms (the Pond-B group) after transfer to the RAS were evaluated in pond-nursed fry. Their survival and morphometric indices were monitored after the RAS habituation period (first 10 days), after the 18-day post-habituation period and after an additional 30 days of on-grow. Our results indicate a negative allometric growth of the pond-nursed fish during the nursing period, which was slower (p < 0.0001) in comparison to the RAS-nursed fry (16.3 ± 0.4 vs. 17.8 ± 0.7%/day). After transfer, these fish grew faster than the RAS-nursed fry (7.7 ± 0.1, 4.9 ± 0.5 and 6.1 ± 0.6 during habituation, 8.5 ± 0.6, 9.3 ± 0.5 and 6.7 ± 0.1%/day during post-habituation period, in the Pond-B, Pond-D and RAS groups, respectively). However, four weeks afterwards, the RAS-nursed fry were again superior in terms of growth (4.0 ± 0.1, 3.6 ± 0.2 and 4.6 ± 0.2%/day, for the Pond-B, Pond-D and RAS groups, respectively), and this was accompanied by a significantly lower feed conversion ratio in this group. Although the survival of the RAS-nursed fry during the nursing period was lower in comparison to the pond-reared fry (11.3 vs. 67.3%), the RAS seems to provide a long-term growth advantage.

Chemical Profiling and Antioxidant Activity of Tanacetum vulgare L. Wild-Growing in Latvia.

The Tanacetum vulgare L. (Tansy) has several ethnobotanical uses, mostly related to the essential oil and sesquiterpene lactones, whereas information regarding other compounds is scarce. This research is designed to characterize the phenolic compounds (flavonoids, phenolic acids, and tannins) to analyze the thujone (which is toxic in high concentrations) content and to detect the antioxidant activity (DPPH assay) of extracts. The main highlights of our work provide a chemical profile of phenolic compounds of T. vulgare harvested from different regions of Latvia, as well as simultaneously support the ethnomedicinal uses for wild T. vulgare through the integration of phenolic compounds as one of the value constituents of leaves and flowers. The extraction yield was 18 to 20% for leaves and 8 to 16% for flowers. The total phenol content in the extracts of T. vulgare as well as their antioxidant activity was different between collection regions and the aerial parts ranging from 134 to 218 mg GAE/g and 32 to 182 mg L-1, respectively. A remarkable variation in the thujone (α + ß) content (0.4% up to 6%) was detected in the extracts. T. vulgare leaf extracts were rich in tannins (up to 19%). According to the parameters detected, the extracts of T. vulgare could be considered promising for the development of new herbal products.

Evaluation of Oleogels Stabilized by Particles of Birch Outer Bark Extract through a Novel Approach.

Structuring liquid oils into oleogels using natural and abundant biomass components as gelling agents is of great significance in fields such as foods, pharmaceuticals, and cosmetics. In this work, a more energy-efficient and technologically simpler approach for directly preparing birch outer bark extract particles containing oleogel was used. This method involves introducing birch outer bark extract particles into the oil phase directly from the extract solution, combining both the evaporation of solution and gel formation. As a result, stable oleogels of various vegetable oils (sunflower, almond, olive, and hemp seed) were obtained with birch outer bark extract particle contents of 4-10%. Infrared spectroscopy and particle size analysis confirmed that when increasing the content of extract particles in the oil, increasing self-assembly of extract particles via hydrogen bonding occurs, leading to the formation of a more structured network. This is consistent with gel strength values from rheological tests of oleogels, which also increased with particle concentration. The obtained oleogels showed important properties such as good tolerance to time-dependent deformation, shear thinning, and thermoreversibility.

Evaluation of Post-Larval Diets for Indoor Weaned Largemouth Bass (Micropterus salmoides).

This study aimed to evaluate different commercial diets (Otohime C1, Aller Futura (AF), Biomar Inicio Plus (BIP)) and one experimental feed (EF) in terms of their effectiveness as post-larval diets for indoor weaned largemouth bass, LMB (Micropterus salmoides). Key variations in the content of nutritive values were monounsaturated fatty acid (MUFA) and highly unsaturated FA (HUFA) ω3. Fish were fed with one of four tested diets from the 33rd to the 40th day post-hatch (DPH). Biometric indices, digestive enzyme-specific activities, thyroid hormone status, and mRNA expression of genes coding for skeleton, neuron, and muscle growth were analyzed. The lowest skeletal deformity rate and highest survival among the treatments were seen in BIP-fed fish. Dietary lipids, with an appropriate balance between MUFA and polyunsaturated FA (PUFA), alongside amino acid balance, were shown to be the main contributors to the growth of the skeleton and/or fish survival. On the other hand, fish growth is correlated with fish digestive capacity and feed moisture percent rather than feed quality. Unexpectedly, BIP-fed fish were attributed with the lowest expression of skeleton differentiation markers, which may reflect the sacrifice of scale and/or cranium growth at the expense of somatic growth. This study highlights the role of non-marine ingredients in the nutrition of post-larval LMB.

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy.

Introduction: Therapeutic treatment for advanced-stage (T2-T4) gastroesophageal junction (GEJ) and gastric cancer involves neoadjuvant chemotherapy with subsequent surgical intervention. Method: Neoadjuvant oncological treatment for GEJ and gastric cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group 1). The new protocol (FLOT, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), included patients with resectable GEJ and gastric cancer who had a clinical stage cT2 or higher nodal positive cN+ disease (Group 2). Between 31 December 2008 and 31 October 2022, the effect of different oncological protocols in terms of surgical outcomes in cases of T2-T4 tumours were retrospectively evaluated. Results of randomly assigned patients from the earlier ECF/ECX protocol (n = 36) (Group 1) and the new FLOT protocol (n = 52) (Group 2) were compared. Effect of different neoadjuvant therapies on tumour regression, types of possible side effects, type of surgery, and oncological radicality of surgical procedures were analysed. Results: When comparing the two groups, we found that in case of the FLOT neoadjuvant chemotherapy (Group 2, n = 52), complete regression was achieved in 13.95% of patients, whereas in the case of ECF/ECX (Group 1, n = 36), complete regression occurred in only 9.10% of patients. Furthermore, in the FLOT group, the mean number of lymph nodes removed was slightly higher (24.69 vs. 20.13 in the ECF/ECX group). In terms of the safety resection margin (proximal), no significant difference was found between the two treatment groups. Nausea and vomiting were the most common side effects. The occurrence of diarrhea was significantly higher in the FLOT group (p = 0.006). Leukopenia and nausea occurred more commonly with the old protocol (Group 1). The rate of neutropenia was lower following FLOT treatment (p = 0.294), with the lack of grade II and III cases. Anaemia occured at a significantly higher rate (p = 0.036) after the ECF/ECX protocol. Conclusions: As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-esophageal junction and gastric cancer, the rate of complete tumour regression increased significantly. The rate of side effects was also appreciably lower following the FLOT protocol. These results strongly suggest a significant advantage of the FLOT neoadjuvant treatment used before surgery.