Investigating the Effect of the Crosslinking Factor on the Properties of Hydrogel Materials Containing Tilia platyphyllos Hydrolate.

The use of natural ingredients in recent years has been of great importance in many industries and medicine. In biomedical applications, hydrogel materials also play a significant role. In view of this, the aim of this study was to synthesize and characterize hydrogel materials enriched with broadleaf linden hydrolate. An important aspect was to carry out a series of syntheses with varying types and amounts of crosslinking agents so as to test the possibility of synthesizing materials with controlled properties. The obtained hydrogels were subjected to detailed physicochemical analysis. The results of the tests confirmed the relationship between the selected properties and the type of crosslinking agent used. A crosslinking agent with a lower molar mass (575 g/mol) results in a material with a compact and strongly crosslinked structure, which is characterized by high surface roughness. The use of a crosslinking agent with a molecular weight of 700 g/mol resulted in a material with a looser-packed polymer network capable of absorbing larger amounts of liquids. The work also proved that regardless of the type of crosslinking agent used, the addition of linden hydrolate provides antioxidant properties, which is particularly important in view of the target biomedical application of such materials.

Investigation of Physicochemical Properties and Surface Morphology of Hydrogel Materials Incorporating Rosehip Extract.

Hydrogel materials are used in many fields of science and industry. They are of particular importance in biomedical applications. In this work, hydrogels were obtained that could act as a dressing for wounds, at the same time being a carrier of substances with antioxidant activity. The discussed materials were obtained in the field of UV radiation. The correlation between the amount of photoinitiator used and the physicochemical properties and surface morphology of the obtained materials was investigated. In addition, the hydrogels have been incorporated with wild rose extract, which is characterized by antioxidant and anti-inflammatory effects. The analysis of the sorption capacity confirmed that the obtained material is able to absorb significant amounts of incubation fluids, which, in terms of application, will enable the absorption of exudate from the wound. The highest stability of materials was noted for hydrogels obtained with the use of intermediate amounts of photoinitiator, i.e., 50 µL and 70 µL. In the case of using 20 µL or 100 µL, the photopolymerization process did not proceed properly and the obtained material was characterized by a lack of homogeneity and high brittleness. With the increase in the amount of photoinitiator, an increase in the surface roughness of hydrogel materials was confirmed. In turn, spectroscopic analysis ruled out the degradation of materials in incubation fluids, indicating the potential for their use in biomedical applications.

Analysis of the Influence of Both the Average Molecular Weight and the Content of Crosslinking Agent on Physicochemical Properties of PVP-Based Hydrogels Developed as Innovative Dressings.

Hydrogels belong to the group of polymers with a three-dimensional crosslinked structure, and their crosslinking density strongly affects their physicochemical properties. Here, we verified the impact of both the average molecular weight of crosslinking agents used during the photopolymerization of hydrogels and that of their content on selected properties of these materials. First, PVP-based hydrogels modified with Aloe vera juice and L-ascorbic acid were prepared using UV radiation. Next, their surface morphology was characterized via optical scanning electron microscopy, whereas their chemical structure was investigated by FT-IR spectroscopy. Moreover, we verified the tendency of the hydrogels to degrade in selected physiological liquids, as well as their tensile strength, percentage of elongation, and swelling capability. We found that the more crosslinking agent in the hydrogel matrix, the higher its tensile strength and the less elongation. The hydrogels showed the highest stability during incubation in SBF and 2% hemoglobin solution. A sharp decrease in the pH of distilled water observed during the incubation of the hydrogels was probably due to the release of Aloe vera juice from the hydrogel matrices. This was additionally confirmed by the decrease in the intensity of the absorption band derived from the polysaccharides included in this additive and by the decrease in the swelling ratio after 48 h. Importantly, all hydrogels demonstrated swelling properties, and it was proven that the higher content of the crosslinking agent in hydrogels, the lower their swelling ability.

Studies on the Impact of the Photoinitiator Amount Used during the PVP-Based Hydrogels' Synthesis on Their Physicochemical Properties.

In recent times, a great interest is directed to developing biomaterials incorporated with various therapeutical substances which may enhance them with new properties and thus increase their application potential. In this work, polyvinylpyrrolidone (PVP)-based hydrogels modified with Aloe vera juice and vitamin C and differing in the amount of the photoinitiator used during their synthesis were developed. Analysis of hydrogels included characterization of their chemical structure via FT-IR spectroscopy, sorption properties, wettability, surface morphology, behavior in simulated physiological liquids and mechanical properties. Finally, hydrogels' cytotoxicity towards L929 murine fibroblasts using MTT reduction assay was additionally verified. It was demonstrated that as the amount of the photoinitiator used during the synthesis of hydrogels increased, the smoother their surface and the higher their hydrophilicity. Next, the greater the amount of the photoinitiator, the lower is the percentage elongation of the hydrogel and the greater the hardness. In turn, the swelling ability of hydrogels depended strongly on the type of the absorbed liquid-swelling ratios of samples in distilled water were 24% higher than in SBF, 18% higher than in Ringer liquid, and 32% higher than in hemoglobin wherein the amount of the photoinitiator did not affect this property. Additionally, hydrogels were stable and did not degrade in simulated physiological liquids. The only changes in pH of the incubation media were probably caused by the active substances release from hydrogels which was also confirmed via a lesser intensity of the absorption band on FT-IR spectra corresponding to the functional group occurring in compounds included in Aloe vera juice. Importantly, the viability of fibroblasts incubated with developed materials was at least 86%. Thus the hydrogels, due to their properties, seem to show application potential to be used for biomedical purposes, e.g., as innovative dressing materials.

Physicochemical Evaluation of L-Ascorbic Acid and Aloe vera-Containing Polymer Materials Designed as Dressings for Diabetic Foot Ulcers.

Hydrogels belong to the group of polymers that are more and more often considered as innovative dressing materials. It is important to develop materials showing the most advantageous properties from the application viewpoint wherein in the case of hydrogels, the type and the amount of the crosslinking agent strongly affect their properties. In this work, PVP-based hydrogels containing Aloe vera juice and L-ascorbic acid were obtained via UV-induced polymerization. Next, their surface morphology (via both optical, digital and scanning electron microscope), sorption capacity, tensile strength, and elongation were characterized. Their structure was analyzed via FT-IR spectroscopy wherein their impact on the simulated body liquids was verified via regular pH and temperature measurements of these liquids during hydrogels' incubation. It was demonstrated that as the amount of the crosslinker increased, the polymer structure was more wrinkled. Next, hydrogels showed relatively smooth and only slightly rough surface, which was probably due to the fact that the modifiers filled also the outer pores of the materials. Hydrogels demonstrated buffering properties in all incubation media, wherein during the incubation the release of Aloe vera juice probably took place as evidenced by the decrease in the pH of the incubation media and the disappearance of the absorption band deriving from the polysaccharides included in the composition of this additive. Next, it was proved that as the amount of the crosslinker increased, hydrogels' crosslinking density increased and thus their swelling ratio decreased. Hydrogels obtained using a crosslinking agent with higher average molecular weight showed higher swelling ability than the materials synthesized using crosslinker with lower average molecular weight. Moreover, as the amount of the crosslinking agent increased, the tensile strength of hydrogels as well as their percentage elongation also increased.

Iron Oxide Magnetic Nanoparticles with a Shell Made from Nanosilver-Synthesis Methodology and Characterization of Physicochemical and Biological Properties.

The interest in magnetic nanoparticles is constantly growing, which is due to their unique properties, of which the most useful is the possibility of directing their movement via an external magnetic field. Thus, applications may be found for them as carriers in targeted drug delivery. These nanomaterials usually form a core in a core-shell structure, and a shell may be formed via various compounds. Here, nanosilver-shelled iron oxide magnetic nanoparticles were developed. Various reaction media and various Arabic gum (stabilizer) solution concentrations were investigated to verify those that were most beneficial one in limiting their agglomeration as much as possible. The essential oil of lavender was proposed as a component of such a medium; it was used alone or in combination with distilled water as a solvent of the stabilizer. The particle size was characterized by dynamic light scattering (DLS), the chemical structure was characterized via FT-IR spectroscopy, the crystallinity was characterized by X-ray diffraction (XRD), and the surface morphology and elemental composition were verified via the SEM-EDS technique. Moreover, UV-Vis spectrophotometry was used to verify the presence of the shell made of nanosilver. Importantly, the particles' pro-inflammatory activity and cytotoxicity towards L929 murine fibroblasts were also characterized. It was demonstrated that a 3% stabilizer solution provided a preparation of Fe3O4@Ag particles, but its stabilizing effect was not sufficient, as a suspension with micrometric particles was obtained; thus it was necessary to apply 4 h of sonication for their crushing. Next, the oil/water reaction medium was verified as beneficial in terms of nanoparticle formation. In such reaction conditions, the formation of particle agglomerates was strongly limited, and after 15 min of sonication a suspension containing only nanoparticles was obtained. The presence of a nanosilver shell was confirmed spectrophotometrically via XRD and SEM-EDS techniques. Importantly, the developed nanomaterials showed no cytotoxicity towards murine fibroblasts and no pro-inflammatory activity.

The Synthesis Methodology and Characterization of Nanogold-Coated Fe3O4 Magnetic Nanoparticles.

Core-shell nanostructures are widely used in many fields, including medicine and the related areas. An example of such structures are nanogold-shelled Fe3O4 magnetic nanoparticles. Systems consisting of a magnetic core and a shell made from nanogold show unique optical and magnetic properties. Thus, it is essential to develop the methodology of their preparation. Here, we report the synthesis methodology of Fe3O4@Au developed so as to limit their agglomeration and increase their stability. For this purpose, the impact of the reaction environment was verified. The properties of the particles were characterized via UV-Vis spectrophotometry, dynamic light scattering (DLS), X-ray diffraction (XRD), and Scanning Electron Microscopy-Energy Dispersive X-ray analysis (SEM-EDS technique). Moreover, biological investigations, including determining the cytotoxicity of the particles towards murine fibroblasts and the pro-inflammatory activity were also performed. It was demonstrated that the application of an oil and water reaction environment leads to the preparation of the particles with lower polydispersity, whose agglomerates' disintegration is 24 times faster than the disintegration of nanoparticle agglomerates formed as a result of the reaction performed in a water environment. Importantly, developed Fe3O4@Au nanoparticles showed no pro-inflammatory activity regardless of their concentration and the reaction environment applied during their synthesis and the viability of cell lines incubated for 24 h with the particle suspensions was at least 92.88%. Thus, the developed synthesis methodology of the particles as well as performed investigations confirmed a great application potential of developed materials for biomedical purposes.

A preliminary evaluation of oxidative stress in patients with gastric cancer before chemotherapy.

Introduction: Due to an imbalanced redox status, cancer cells generate intrinsically higher levels of reactive oxygen species (ROS) compared to normal cells. Targeting ROS is an important therapeutic strategy for cancer as exemplified by cancer drugs, which induce ROS-dependent synergistic cytotoxicity in gastric cancer cells. The present study was designed to assess the level of selected oxidative stress biomarkers in blood plasma derived from gastric cancer patients. Material and methods: The study assessed the oxidative/nitrative biomarkers in blood plasma isolated from 51 gastric (adenocarcinoma) cancer patients, compared to a control group of 32 healthy volunteers. Oxidative stress was evaluated using a panel of biomarkers such as plasma protein thiol groups and 3-nitrotyrosine levels as well as indicators of plasma lipid peroxidation, i.e. lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS). Additionally, the total antioxidant capacity of blood plasma (non-enzymatic capacity of blood plasma, NEAC) was also estimated. Results: Our results showed that patients with gastric cancer had significantly different levels of thiol groups (lower, p < 0.001) and 3-nitrotyrosine (higher, p < 0.0001), LOOH (higher, p < 0.05), TBARS (higher, p < 0.05), NEAC (lower, p < 0.0001), compared to the control group. Conclusions: The present study indicates considerable oxidative/nitrative stress in gastric cancer patients. Our pilot study shows that not a single marker, but a biomarker panel, may be a more reliable representation of oxidative stress in patients with gastric cancer.

Silver Nanoparticles and Glycyrrhiza glabra (Licorice) Root Extract as Modifying Agents of Hydrogels Designed as Innovative Dressings.

The interest in the application of plant extracts as modifiers of polymers intended for biomedical purposes is constantly increasing. The therapeutical properties of the licorice root, including its anti-inflammatory and antibacterial activity, make this plant particularly promising. The same applies to silver nanoparticles showing antibacterial properties. Thus the main purpose of the research was to design hydrogel dressings containing both licorice root extract and nanosilver so as to obtain a system promoting wound regeneration processes by preventing infection and inflammation within the wound. The first step included the preparation of the plant extract via the solid-liquid extraction using the Soxhlet extractor and the synthesis of silver nanoparticles by the chemical reduction of silver ions using a sodium borohydride as a reducing agent. Subsequently, hydrogels were synthesized via photopolymerization and subjected to studies aiming at characterizing their sorption properties, surface morphology via scanning electron microscopy, and their impact on simulated physiological liquids supported by defining these liquids' influence on hydrogels' structures by FT-IR spectroscopy. Next, the tensile strength of hydrogels and their percentage elongation were determined. Performed studies also allowed for determining the hydrogels' wettability and free surface energies. Finally, the cytotoxicity of hydrogels towards L929 murine fibroblasts via the MTT reduction assay was also verified. It was demonstrated that developed materials showed stability in simulated physiological liquids. Moreover, hydrogels were characterized by high elasticity (percentage elongation within the range of 24-29%), and their surfaces were hydrophilic (wetting angles below 90°). Hydrogels containing both licorice extract and nanosilver showed smooth and homogeneous surfaces. Importantly, cytotoxic properties towards L929 murine fibroblasts were excluded; thus, developed materials seem to have great potential for application as innovative dressings.

Overall survival of patients with EGFR mutation-positive non-small-cell lung cancer treated with erlotinib, gefitinib or afatinib under drug programmes in Poland - real-world data.

INTRODUCTION: The aim of the study was to estimate the overall survival of patients with EGFR mutation-positive non-small-cell lung cancer treated with erlotinib, gefitinib or afatinib. MATERIAL AND METHODS: Real-world patients who received afatinib, erlotinib or gefitinib between 1 July 2012 and 30 October 2017 were analysed in five subgroups. RESULTS: Among 267 patients treated with afatinib financed as the first line of treatment, 76 (28.46%) deaths occurred. Median observation time was 12.8 months (95% CI: 11.2-13.9). Median OS was 22.8 months (95% CI: 19.2-27.1). Among 83 patients who received erlotinib financed exclusively as the second line of treatment the number of deaths was 74 (89.16%). Median observation time was 64.3 months (95% CI: 60.4-64.6). Median OS was 16 months (95% CI: 13.2-22.9). Among 622 patients who received erlotinib financed both as first and second line treatment, there were 400 (64.3%) deaths. Median observation time was 33.3 months (95% CI: 31.2-37.6). Median OS was 17.8 months (95% CI: 16.4-19.7). Among 137 patients who received gefitinib financed only as the first line of treatment, there were 128 (93.4%) deaths. Median observation time was 58.3 months (95% CI: 49.4-62.5). Median OS was 16 months (95% CI: 13.8-19.7). Among 348 patients who received gefitinib financed both as the first and second line of treatment the number of deaths was 208 (59.8%). Median observation time was 23.7 months (95% CI: 20.7-28.7). Median OS was 15.5 months (95% CI: 12.9-17.5). CONCLUSIONS: Our real-world data regarding OS confirm the benefits found in clinical trials from the use of afatinib, erlotinib or gefitinib. However, the lower overall survival rate of Polish patients compared to similar studies from other research centres suggests the need for deeper investigation of this issue.

CAR-NK Cells in the Treatment of Solid Tumors.

CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, the treatment is far from flawless. Its greatest drawbacks arise from a challenging and expensive production process, strict patient eligibility criteria and serious toxicity profile. One possible solution, supported by robust research, is the replacement of T lymphocytes with NK cells for CAR expression. NK cells seem to be an attractive vehicle for CAR expression as they can be derived from multiple sources and safely infused regardless of donor-patient matching, which greatly reduces the cost of the treatment. CAR-NK cells are known to be effective against hematological malignancies, and a growing number of preclinical findings indicate that they have activity against non-hematological neoplasms. Here, we present a thorough overview of the current state of knowledge regarding the use of CAR-NK cells in treating various solid tumors.

Remission of Thymoma on Steroid Therapy in a Patient With Atypical Thymoma-Associated Multiorgan Autoimmunity: A Case Report and Literature Review.

In up to 34% of cases, thymoma, itself a rare neoplasm, is accompanied by autoimmune disorders, two of which are thymoma-associated multiorgan autoimmunity (TAMA) and paraneoplastic autoimmune multiorgan syndrome (PAMS). Unfortunately, differential diagnosis between these two entities can be challenging since no strict PAMS definition exists and PAMS can overlap with a subgroup of TAMA patients with skin lesions as leading presentation. We present a case of a 68-year-old woman with a diagnosis of thymoma accompanied by myasthenia gravis, hypothyroidism and GvHD-like mucocutaneous lesions that initially could account to both TAMA and PAMS diagnosis. However, following the exclusion of humoral autoimmunity against components of epithelial cells junction, TAMA was finally established. Interestingly, the introduction of corticosteroid therapy for TAMA symptom management resulted in unexpected partial remission of thymoma with no impact on mucocutaneous lesions. Our case study is an example of two extremely rare phenomena accompanying thymomas: unprecedented TAMA presentation with GvHD-like mucositis, which as we postulate should be placed in the spectrum of TAMA, and tumor remission on steroids.

The Synthesis Methodology of PEGylated Fe3O4@Ag Nanoparticles Supported by Their Physicochemical Evaluation.

Many investigations are currently being performed to develop the effective synthesis methodology of magnetic nanoparticles with appropriately functionalized surfaces. Here, the novelty of the presented work involves the preparation of nano-sized PEGylated Fe3O4@Ag particles, i.e., the main purpose was the synthesis of magnetic nanoparticles with a functionalized surface. Firstly, Fe3O4 particles were prepared via the Massart process. Next, Ag+ reduction was conducted in the presence of Fe3O4 particles to form a nanosilver coating. The reaction was performed with arabic gum as a stabilizing agent. Sound energy-using sonication was applied to disintegrate the particles' agglomerates. Next, the PEGylation process aimed at the formation of a coating on the particles' surface using PEG (poly(ethylene glycol)) has been performed. It was proved that the arabic gum limited the agglomeration of nanoparticles, which was probably caused by the steric effect caused by the branched compounds from the stabilizer that adsorbed on the surface of nanoparticles. This effect was also enhanced by the electrostatic repulsions. The process of sonication caused the disintegration of aggregates. Formation of iron (II, III) oxide with a cubic structure was proved by diffraction peaks. Formation of a nanosilver coating on the Fe3O4 nanoparticles was confirmed by diffraction peaks with 2θ values 38.15° and 44.35°. PEG coating on the particles' surface was proven via FT-IR (Fourier Transform Infrared Spectroscopy) analysis. Obtained PEG-nanosilver-coated Fe3O4 nanoparticles may find applications as carriers for targeted drug delivery using an external magnetic field.

Leukemia Inhibitory Factor: A Potential Biomarker and Therapeutic Target in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, treatment-resistant cancer. Five-year survival rate is about 9%, one of the lowest among all solid tumors. Such a poor outcome is partly due to the limited knowledge of tumor biology, and the resulting lack of effective treatment options and robust predictive biomarkers. The leukemia inhibitory factor (LIF) has recently emerged as a potential biomarker and therapeutic target for PDAC. Accumulating evidence has suggested that LIF plays a role in supporting cancer evolution as a regulator of cell differentiation, renewal and survival. Interestingly, it can be detected in the serum of PDAC patients at higher concentrations than healthy individuals, this supporting its potential value as diagnostic biomarker. Furthermore, preliminary data indicate that testing for LIF serum concentration or tissue expression may help with treatment response monitoring and prognostication. Finally, studies in PDAC mouse models have also shown that LIF may be a valuable therapeutic target, and first-in-human clinical trial is currently ongoing. This article aims to review the available data on the role of LIF in PDAC promotion, and to discuss the evidence supporting its potential role as a biomarker and target of effective anti-cancer therapy in this setting.

Cardiovascular risk factors among cancer patients qualified for systemic treatment. Analysis of a cardiovascular disease-free cohort from the Polish multicentre study ONCOECHO.

INTRODUCTION: Cancer therapies are currently more efficient at increasing the survival of patients (pts) with cancer. Unfortunately, the cardiovascular (CV) complications of cancer therapies may adversely affect improving results of treatment. The aim of the study was to evaluate the prevalence of classical CV risk factors among pts with de novo diagnosis of cancer and thus identify the cohort of pts with potentially increased future risk of CV complications. MATERIAL AND METHODS: The analysis is based on the database of the multicentre ONCOECHO study. Pts before systemic treatment (chemotherapy or targeted therapy) were included. The diagnostic datasets of resting electrocardiogram, blood samples, and transthoracic echocardiogram were analysed in 343 consecutive pts who were free from any cardiovascular disease that could adversely affect the introduced treatment. RESULTS: Our cohort included 4.4% of pts with kidney cancer, 7.3% with colorectal cancer, 26.5% with haematological malignancies (HM), and 61.8% with breast cancer. The risk estimated by SCORE was 4.56 ±5.07%. Breast cancer pts had lower cardiovascular risk than those with HM (p = 0.001) and kidney cancer (p = 0.002). Additionally, the HM group had much higher levels of natriuretic peptides (p < 0.001) and creatinine (p = 0.008) than pts with breast cancer. The comparison with the NATPOL population data showed that our pts were more often smokers, hypertensives, and diabetics, but less frequently presented with hypercholesterolaemia. CONCLUSIONS: Patients with new diagnosis of cancer, who are candidates for potentially cardiotoxic medical treatment, have increased prevalence of significant cardiovascular risk factors and therefore should be followed by a multidisciplinary team during the therapeutic process.

Analysis of the survival of patients receiving systemic treatment for melanoma of the skin: a retrospective population study with patients treated in Poland in 2011-2015.

INTRODUCTION: In Poland, it is uniquely possible to assess real effects of the introduction of new oncological therapies on the overall survival in patients as such therapies are funded by one payer only - the National Health Fund (NHF). Data collected by the NHF make it possible to analyse the survival of all patients who were diagnosed with melanoma. AIM: The paper presents findings of a retrospective analysis of the efficacy of systemic treatment in patients with malignant melanoma of the skin in Poland with regard to the overall survival. MATERIAL AND METHODS: The analysis of the overall survival was performed with the Kaplan-Meier method in the population receiving systemic treatment. Three groups of patients were analysed. Group 1 included all patients who had started systemic treatment between 1 March 2011 and 1 March 2015: 1,258 patients. The median overall survival was 8.4 months. Group 2 included 444 patients who had started systemic treatment between 1 March 2011 and 28 February 2013. The median overall survival was 6.6 months in this group. Group 3 included 814 patients who had started systemic treatment between 1 March 2013 and 1 March 2015 and included 546 patients who were also treated in drug programmes with ipilimumab and vemurafenib (approx. 67%). The median overall survival was 9.4 months. RESULTS: A difference in the overall survival between group 3 and 2 was statistically significant (p < 0.05). CONCLUSIONS: The introduction of vemurafenib and ipilimumab into systemic treatment in Poland using public funds had a significant effect on the prolongation of the overall survival in patients with malignant melanoma of the skin.

Real-World Evidence of Patient Outcome Following Treatment of Advanced Gastrointestinal Stromal Tumor (GIST) with Imatinib, Sunitinib, and Sorafenib in Publicly Funded Health Care in Poland.

BACKGROUND This study aimed to undertake an analysis of ten years of real-world evidence (RWE) on overall survival (OS) following treatment of advanced gastrointestinal stromal tumor (GIST) with imatinib, sunitinib, and sorafenib using data from the Polish National Health Fund. MATERIAL AND METHODS Data from the Polish National Health Fund, the sole Polish public payer, identified 1,641 patients with advanced GIST who were treated with imatinib (n=1047), sunitinib (n=457), and sorafenib (n=137). The differences in overall survival (OS) were analyzed. RESULTS For patients with advanced GIST, the median follow-up time for patients treated with imatinib was 71 months (95% CI, 64.8-79.2), the median OS was 56.9 months (95% CI, 50.4-61.2), with survival at 12 months (89.5%), 24 months (77.9%), 36 months (66.9%), and 60 months (48.4%). The median follow-up time for patients treated with sunitinib was 41.4 months (95% CI, 34.6-49.3), the median OS was 22.8 months (95% CI, 19.2-26.8), with survival at 12 months (68.2%), 24 months (47.1%), and 36 months (31%). The median follow-up time for patients treated with sorafenib was 17.4 months (95% CI, 14.6-22.9), the median OS was 16.9 months (95% CI, 13.7-24.3), with survival at 12 months (61.9%), at 24 months (36.2%), and at 36 months (16.8%). CONCLUSIONS Real-world data collected in a ten-year period confirmed the effectiveness of the use of imatinib, sunitinib, or sorafenib for the treatment of advanced GIST and was comparable with the findings from clinical trials.

Tetraspanin CD151 impairs heterodimerization of ErbB2/ErbB3 in breast cancer cells.

CD151/Tspan24 (SFS-1, PETA3) is one of the best characterized members of the tetraspanin family, whose involvement in breast cancer (BCa) progression was demonstrated both in vitro and in vivo. We have recently reported that in ErbB2-overexpressing BCa cells grown in 3D laminin-rich extracellular matrix, CD151 regulated basal phosphorylation and homodimerization of ErbB2 and sensitized the cells to Herceptin (trastuzumab). Following from these data, we have here analyzed an involvement of CD151 in regulation of ErbB2/ErbB3 heterodimerization and its impact on cell response to Herceptin. CD151 was found to: (1) impair ErbB2/ErbB3 heterodimerization, (2) inhibit heregulin-dependent cell growth in 3D and signaling, and (3) counteract the protective effect of heregulin on Herceptin-mediated growth inhibition. Analysis of tissue samples demonstrated for the first time clinical significance of CD151 in patients with ErbB2-overexpressing BCa undergone trastuzumab-based therapy. Consistent with in vitro results, CD151 impact on disease outcome was ErbB3-dependent. In patients with ErbB3-negative tumors, CD151 significantly improved both overall survival (OS) (hazard ratio [HR] = 0.19, P = 0.034) and progression-free survival (PFS) (HR = 0.36, P = 0.043), while in ErbB3-positive cases it had no significant effect on patient survival (OS: HR = 3.33, P = 0.283; PFS: HR = 2.40, P = 0.208). These results support previous findings and show that CD151 acts as an important component of ErbB2 signaling axis in BCa cells, affecting their sensitivity to ErbB2-targeting therapy.

The prognostic impact of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patients with advanced colorectal cancer treated with first-line chemotherapy.

INTRODUCTION: Colorectal cancer is the second most frequently diagnosed malignancy and one of the leading causes of cancer-related death in Poland. Many reports of different types of cancer have indicated that blood count parameters may serve as a source of prognostic or predictive information. AIM: To assess the association between these parameters and clinical outcome in patients with advanced colorectal cancer. MATERIAL AND METHODS: We retrospectively analysed a database of 295 patients with advanced colorectal cancer treated with first-line palliative chemotherapy at our institution from January 2008 to December 2012. Blood-based parameters were measured before the first cycle of treatment. RESULTS: The median progression-free survival (PFS) was 6.7 months, and the median overall survival was 17.6 months. A high neutrophil-to-lymphocyte ratio (NLR) and a high platelet-to-lymphocyte ratio (PLR) were associated with a shorter survival (hazard ratio (HR): 1.88, p < 0.0001 for the NLR and HR: 1.39, p = 0.0054 for the PLR), but for the PLR, we observed only a not significant trend toward a worse PFS (HR = 1.25, p = 0.07 for the PLR and HR = 1.55, p = 0.0004 for the NLR). A high lymphocyte-to-monocyte ratio (LMR) was associated with a better prognosis (HR = 0.58, p ≤ 0.0001) and a longer PFS (HR = 0.73, p = 0.011). CONCLUSIONS: The blood-based parameters are readily available, reliable, and low-cost biomarkers, which can be easily incorporated into routine practice to predict the prognosis in patients with advanced colorectal cancer.