An unusual non­metastatic, mismatch repair­deficient primary gastric squamous cell carcinoma presenting as a large, exophytic, bleeding tumor: A case report.

Primary gastric squamous cell carcinoma (GSCC) is an extremely rare malignancy with a poor prognosis. Despite the improved knowledge regarding its pathogenesis and biology, the treatment options remain limited. The present study reported on the unique case of a mismatch repair-deficient (dMMR) primary GSCC in a 79-year-old woman reporting fatigue and symptoms of upper gastrointestinal tract bleeding. Physical examination revealed abdominal pain at palpation. Gastroscopy revealed a large, exophytic, bleeding tumor. Medical imaging confirmed a mushroom-like polyp in the lumen of the stomach, with no signs of disease spread. Total gastrectomy and D2 lymphadenectomy were performed. Pathological examination of the post-operational material confirmed a well-differentiated SCC invading the mucosa, submucosa and muscle layer. There were no signs of dissemination observed in any of the 32 excised lymph nodes. Notably, according to the last follow-up, the patient remains well, supporting the 5-year GSCC survival rate statistics. To the best of our knowledge, this is the first such GSCC case reported in the Surgical Oncology Outpatient Clinic (Copernicus Memorial Hospital, Lodz, Poland) and these findings add to the limited data on GSCC. Although this is a very rare condition, it should always be considered during the process of diagnosis of gastric tumors.

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience.

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07−0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09−0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.

The effect of l-arginine supplementation and surgical trauma on the frequency of myeloid-derived suppressor cells and T lymphocytes in tumour and blood of colorectal cancer patients.

PURPOSE: l-arginine (L-arg) deficiency causes immunosuppression, but it is unknown if L-arg supplementation in colorectal cancer (CRC) patients restores immune system activity. Our objective was to investigate the effect of L-arg supplementation on the frequency of monocytic (M) and polymorphonuclear (PNM) myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs, respectively). METHODS: We enrolled 65 CRC patients (34 males, 31 females) aged 69 â€‹± â€‹10 years into a prospective, randomised, double-blind study. Twenty-eight patients received L-arg and 37 received placebo for 9 days at a dose of 10 â€‹g/day. The frequency changes in MDSC, CD4+ cells and the concentration of C-reactive protein (CRP) were assessed before supplementation with L-arg (test 1), after 9 days of supplementation (test 2), and after surgery on day 11 (test 3). RESULTS: The frequency of M-MDSC in the tumours of patients receiving L-arg supplementation was higher than in placebo-treated patients, as was the frequency of PMN-MDSC and M-MDSC in the mucosa. CRP concentration in the serum of placebo-treated patients in test 2 was higher than in test 1, and the concentration in the serum of patients with L-arg supplementation in test 2 was lower than in test 1. Moreover, the expression pattern of the argininosuccinate synthase 1 (ASS1) suggests that CRC is not auxotrophic for L-arg. CONCLUSIONS: The results of this study do not support the hypothesis that L-arg supplementation in CRC patients can reduce immunosuppression by decreasing the frequency of suppressor cells and increasing the frequency of effector CD4+ T cells.

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.

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.

Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP-ALL with PAX5 deletion.

Resistance to L-asparaginase (L-asp) is a major contributor to poor treatment outcomes of several subtypes of childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). Asparagine synthetase (ASNS), legumain (LGMN) and cathepsin B (CTSB) serve a key role in L-asp resistance. The association between genetic subtypes of BCP-ALL and the expression of ASNS, LGMN and CTSB may elucidate the mechanisms of treatment failure. Bone marrow samples of 52 children newly diagnosed with BCP-ALL were screened for major genetic abnormalities and ASNS, LGMN and CTSB gene expression levels. The cohort was further divided into groups corresponding to the key genetic aberrations occurring in BCP-ALL: Breakpoint cluster region and Abelson murine leukemia viral oncogene homolog 1 fusion; hyperdiploidy, hypodiploidy, ETS variant 6 and runt-related transcription factor 1 fusion and other BCP-ALL with no primary genetic aberration identified. A subgroup analysis based on the differences in copy number variations demonstrated a significant increase of ASNS, LGMN and CTSB median expression in other BCP-ALL cases with paired box 5 (PAX5) deletion (P=0.0117; P=0.0036; P<0.0001, respectively) compared with those with wild-type PAX5. Patients with high ASNS expression exhibited longer relapse-free survival (RFS) compared with those with low ASNS levels (P=0.0315; HR, 0.19; 95% CI, 0.04-0.86); the 5-year RFS for patients in the high ASNS expression group was 90.15% (95% CI, 87.90-92.40%). Despite the impact on ASNS, LGMN and CTSB expression, PAX5 deletion did not influence RFS in the other BCP-ALL group (P=0.6839). Therefore, the results of the present study revealed high levels of ASNS, LGMN and CTSB expression in the other BCP-ALL group with concomitant PAX5 deletion and no subsequent deterioration in 5-year RFS. High ASNS expression level, as a single factor, was strongly associated with an improved outcome.

MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL.

Chromosome 21 abnormalities are the most frequent genetic findings in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL) cases. Majority of patients are effectively diagnosed with fluorescence in situ hybridization (FISH) and karyotyping; however, some cases may require additional tools to be used. Bone marrow samples of 373 childhood BCP-ALL patients were tested for chromosome 21 copy number variations (CNVs) with Multiplex Ligation-dependent Probe Amplification (MLPA) P327 array. Results from MLPA and cytogenetics were compared between groups according to the type of abnormality found on chromosome 21. Out the group of 235 patients, chromosome 21 multiplication was found by FISH assay in 56 cases (23.81%), ETV6-RUNX1 fusion in 34 (14.47%) and iAMP21 in 3 (1.28%) children, remaining 142 (60.43%) patients had no known chromosome 21 aberration. Median peak ratios of all tested probes in MLPA in aforementioned groups were 1.47 (IQR 1.28-1.77) vs. 1.00 (IQR 1.00-1.09) vs. 2.79 (IQR 1.97-2.83) vs. 1.00 (1.00-1.11), respectively. Aforementioned peak ratio of ETV6-RUNX1 fusion group was similar with patients of no known chromosome 21 aberration (p = 0.71). Interestingly, both groups differed from patients with chromosome 21 multiplication (p < 10-5) and with iAMP21 (p < 10-5). All cases of iAMP21 were correctly recognized by MLPA. MLPA seems to be good additional tool in the diagnostic process of chromosome 21 CNVs, especially in cases with iAMP21.

Protein-energy wasting and asymmetric dimethylarginine in peritoneal dialysis patients.

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.

Fasting and postprandial acyl and desacyl ghrelin and the acyl/desacyl ratio in obese patients before and after different types of bariatric surgery.

INTRODUCTION: The mechanism underlying beneficial outcomes of bariatric surgery still remains unclear. Especially little is known about hormonal and metabolic changes induced by the novel bariatric procedure mini gastric bypass (MGB). AIM: To evaluate pre- and post-prandial changes in both ghrelin isoforms in obese patients without diabetes and cardiovascular complications treated with MGB, sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. MATERIAL AND METHODS: From 45 patients initially enrolled in the study, 23 persons completed a one-year follow-up period. Venous blood for acyl and desacyl ghrelin (AG and DAG) as well as other metabolic assays was collected 3 months before and 6 and 12 months after bariatric surgery (MGB, RYGB, SG) - in the fasting state and 2 h after the consumption of a standard 300 kcal-mixed meal (Nutridrink standard, Nutricia). RESULTS: AG and DAG levels (both fasting and prandial) as well as AG/DAG ratio did not change after 6 and 12 months in MGB and RYGB groups. In the SG group we observed a significant decrease in fasting and postprandial DAG levels and consecutively an increase in the fasting AG/DAG ratio after 6 and 12 months. Six months after surgery we observed some differences between carbohydrate metabolism measures in the MGB group (lower HbA1c, HOMA-IR and fasting insulinaemia) in comparison to the rest of the participants, but 12 months after each type of surgery body mass index and indices of carbohydrate and lipid metabolism did not differ. CONCLUSIONS: The results of our study demonstrate that all studied bariatric procedures can successfully reduce overall body weight and suggest also that the mechanisms of weight loss and improvement in carbohydrate and lipid metabolism after all three types of surgery are independent of ghrelin and the acyl/desacyl ghrelin ratio.

Iron status and dietary iron intake in vegetarians.

BACKGROUND: Iron is one of the nutrients that require special consideration in a plant-based diet. The widespread belief is that meat is the best source of iron and a vegetarian diet increases the risk of its deficiency. This conviction has been the subject of analysis in a growing number of scientific reports. OBJECTIVES: The aim of this study was to assess the iron intake and iron metabolism in vegetarians and vegans compared to a control group. MATERIAL AND METHODS: A total of 55 vegetarians and 36 healthy volunteers were studied. The following parameters were measured in serum: iron, ferritin, transferrin, transferrin receptor, and hepcidin-25, using the enzyme-linked immunosorbent assay (ELISA) method. The dietary iron intake was assessed by a 24-h dietary recall. RESULTS: The mean daily intake (DI) of iron was significantly higher in the female vegan group compared to the control group. Iron, hepcidin-25, ferritin and transferrin receptor in serum remained within their normal ranges. The ferritin concentration was significantly decreased and that of transferrin significantly higher in both female groups and in the male vegan group. CONCLUSIONS: The obtained results show that the studied parameters, excluding transferrin, remained within normal ranges. However, the ferritin concentration was significantly decreased in the female vegetarian group and also in both vegan groups. This may indicate low iron storage.

Fasting and post-prandial peptide YY levels in obese patients before and after mini versus Roux-en-Y gastric bypass.

BACKGROUNDː The mechanisms underlying the metabolic effect of surgical treatment for morbid obesity are still unclear. Furthermore, the hormonal and metabolic response to the promising and less-invasive version of Roux-en-Y gastric bypass (RYGB), i.e. mini gastric bypass (MGB), is poorly known. The aim of this study was to evaluate pre- and postprandial changes in peptide YY (PYY) and metabolic parameters in obese patients without diabetes and cardiovascular complications treated by both versions of gastric bypass. METHODSː Venous blood for PYY and other assays was collected three months before and six months after bariatric operation (MGB and RYGB), in the fasting state and two hours after the consumption of a standard 300-kcal mixed meal (Nutridrink Standard, Nutricia Advanced Medical Nutrition, part of the Danone company, Schiphol, The Netherlands). RESULTSː In the MGB group, elevated concentrations of the PYY has been detected both fasting and postprandially. The effect of the MGB on the PYY levels did not differ from the RYGB group outcomes. CONCLUSIONSː The results of our study suggest similar endocrine and metabolic effects of MGB and RYGB procedures. Long-term efficacy and metabolic benefits of MGB require further research.

Evaluation of 12-lipoxygenase (12-LOX) and plasminogen activator inhibitor 1 (PAI-1) as prognostic markers in prostate cancer.

In carcinoma of prostate, a causative role of platelet 12-lipoxygenase (12-LOX) and plasminogen activator inhibitor 1 (PAI-1) for tumor progression has been firmly established in tumor and/or adjacent tissue. Our goal was to investigate if 12-LOX and/or PAI-1 in patient's plasma could be used to predict outcome of the disease. The study comprised 149 patients (age 70±9) divided into two groups: a study group with carcinoma confirmed by positive biopsy of prostate (n=116) and a reference group (n=33) with benign prostatic hyperplasia (BPH). The following parameters were determined by the laboratory test in plasma or platelet-rich plasma: protein level of 12-LOX, PAI-1, thromboglobulin (TGB), prostate specific antigen (PSA), C-reactive protein (CRP), hemoglobin (HGB, and hematocrit (HCT), as well as red (RBC) and white blood cells (WBC), number of platelets (PLT), international normalized ratio of blood clotting (INR), and activated partial thromboplastin time (APTT). The only difference of significance was noticed in the concentration of 12-LOX in platelet rich plasma, which was lower in cancer than in BPH group. Standardization to TGB and platelet count increases the sensitivity of the test that might be used as a biomarker to assess risk for prostate cancer in periodically monitored patients.

Isolated coronary artery bypass grafting in extracorporeal circulation in patients over 65 years old - does age still matter?

INTRODUCTION: Coronary artery bypass grafting (CABG) is conducted more and more commonly in patients in advanced age. AIM OF THE STUDY: To analyze the influence of age and concurrent risk factors on the complications and early mortality after CABG. MATERIAL AND METHODS: Medical records of 2194 patients were analyzed retrospectively. A group of 1303 patients who had undergone isolated CABG was selected. 106 (4.8%) patients were excluded due to missing data in their medical records. The remaining 1197 patients were divided into two subgroups by age: 1(st) group < 65 years (n = 662; 55.3%); 2(nd) group ≥ 65 years (n = 535; 44.7%). RESULTS: The total 30-day mortality was 3.93% and was six times higher in the older group (1.21 vs. 7.29%; p < 0.001). Complications were observed in 176 (14.70%) patients, more often in the older group (10.42% vs. 20.0%; p < 0.001). In this group all kinds of complications were noted more often and in particular: postoperative myocardial infarction (1.96% vs. 5.42%; p = 0.001), respiratory dysfunction (1.36% vs. 4.11%; p = 0.005), neurological complications (1.81% vs. 3.74%; p = 0.04) and multi-organ dysfunction syndrome (0.30% vs. 1.68%, p = 0.03). The older patients required longer time under mechanical ventilation (24.0 ± 27.9 vs. 37.0 ± 74.1 hours; p = 0.004) and stayed longer in the intensive care unit: 2.5 ± 3.0 vs. 4.1 ± 7.84 days; p < 0.001. Independent predictors of death were: female sex [OR (95% CI) = 2.4 (1.2-4.5)], age ≥ 65 years [OR = 4.9 (2.1-11.1)], eGFR < 60 mL/min/1.73 m(2) [OR = 2.2 (1.0-4.7)], time at extracorporeal circulation > 72 minutes [OR = 5.5 (2.7-10.9)] and left main stem stenosis (> 50%) [OR = 2.4 (1.3-4.6)]. CONCLUSIONS: Age still significantly influences postoperative complications and mortality after isolated CABG.

Transient protein states in designing inhibitors of the MDM2-p53 interaction.

Reactivation of p53 by release of the functional protein from its inhibition by MDM2 provides an efficient, nongenotoxic approach to a wide variety of cancers. We present the cocrystal structures of two complexes of MDM2 with inhibitors based on 6-chloroindole scaffolds. Both molecules bound to a distinct conformational state of MDM2 with nM-µM affinities. In contrast to other structurally characterized antagonists, which mimic three amino acids of p53 (Phe19, Trp23, and Leu26), the compounds induced an additional hydrophobic pocket on the MDM2 surface and unveiled a four-point binding mode. The enlarged interaction interface of the inhibitors resulted in extension of small molecules binding toward the "lid" segment of MDM2 (residues 19-23)--a nascent element that interferes with p53 binding. As supported by protein engineering and molecular dynamics studies, employing these unstable elements of MDM2 provides an efficient and yet unexplored alternative in development of MDM2-p53 association inhibitors.

The concentration of 12-lipoxygenase in platelet rich plasma as an indication of cancer of the prostate.

AIM OF THE STUDY: The aim of this study was to determine whether measuring concentrations of 12-LOX in platelet-rich plasma patients can:Differentiate between the group of patients with prostate cancer and healthy men.Correlate the degree of severity of the disease and the concentration of the enzyme. MATERIAL AND METHODS: The study group comprised 88 men (40-88 years), including 54 patients diagnosed with prostate cancer. The population was divided into 4 groups:group 1 (22 men, aged 55-84 years) -with a negative biopsy,group 2 (36 men, aged 54-88 years) - with a positive biopsy result,group 3 (18 participants aged 58-83) - patients with cancer metastatic disease,group 4 of healthy men (12 people aged 40-66 years) - biopsy was not performed. Routine PSA, morphology and CRP analysis were performed and platelet rich plasma was used for 12(S)LOX determination using an ELISA kit. RESULTS: There was a weak (r = 0.0487) positive correlation between the number of blood platelets and plasma 12(S)LOX.An inverse relationship between 12(S)LOX and Gleason grade was found.Heterogeneity of 12(S)LOX in the group with prostate cancer metastatic disease may suggest differences in the response to the treatment carried out.There were no statistically significant differences in concentrations of 12(S)LOX in different groups of patients. CONCLUSIONS: Our results suggest that 12(S)LOX is relevant in prostate cancer; however, further study should include a larger, more select group of men with prostate cancer.

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial ß-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

Ischemia-modified albumin as a biochemical marker in children with neuroblastoma and soft tissue sarcomas.

In this study, the levels of ischemia-modified albumin (IMA) in pediatric oncology patients with soft tissue sarcomas (STSs) and neuroblastoma (NB) were analyzed. To date, there have been no studies concerning IMA in these groups of patients. Ninety-nine children with STSs and NB were analyzed from 2006 to 2009, and 30 healthy children were also enrolled in the study. IMA levels were measured throughout treatment in all patients. The levels of IMA in all cancer patients (mean 116.8±39.3 U/ml), in patients with STSs (mean 119.8±27.5 U/ml), and in patients with NB (mean 114.6±36.6 U/ml) were significantly higher than in the control patients (mean 87.3±38.3 U/ml; P=0.0013, 0.0066, and 0.0164, respectively). IMA levels increased before and during the treatment compared with levels in the controls. The determination of IMA levels in pediatric oncology patients with poor prognoses from STSs and NB may play an important role in predicting response to therapy and overall outcome.

The antioxidant status and response to therapy in children with soft tissue sarcomas and neuroblastoma.

BACKGROUND: Antioxidant systems in cells maintain the proper homeostasis of reactive oxygen species, which at high concentrations can induce carcinogenesis. The aim of this study was to evaluate the serum levels of ischemia-modified albumin (IMA), erythrocyte superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) as markers for prognosis in children with neuroblastoma (NB) and soft tissue sarcomas (STS), two cancer types for which reliable prognostic factors are needed. PROCEDURE: SOD, GSH-Px, and IMA were measured before and during responses to therapy assessment in 99 children with NB and STS and in 30 healthy controls. RESULTS: There were no statistically significant differences in the erythrocyte SOD and GSH-Px activities between the patients with cancer and healthy controls. The levels of IMA in patients with STS and NB were found to be significantly higher than in the controls (P = 0.0013; P = 0.0066, and 0.0164, respectively). Decreased activities of SOD and GSH-Px were found in all patients with poor-responding (PRS) cancers and decreased SOD activity was found in patients with PRS NB. An increase in GSH-Px was observed in patients with good-responding (GR) NB. All patients with GR cancers demonstrated higher SOD and GSH-Px activities than patients with PRS cancers. CONCLUSIONS: While determining the levels of specific antioxidants as antioxidant-barrier parameters in children with cancer may be valuable in predicting therapeutic responses as well as outcomes, additional studies are required.

Adipokines, endothelial dysfunction and nutritional status in peritoneal dialysis patients.

OBJECTIVE: Adipokines such as leptin and adiponectin are adipocyte-specific secretory proteins that play important roles in the metabolic regulation of body weight, insulin resistance and cardiovascular complications. The relationship between the malnutrition-inflammation complex syndrome and high levels of some adipokines in peritoneal dialysis (PD) patients is still unclear. An association between high body mass index (BMI) and improved survival in PD patients has also been proposed. The purpose of this study was to investigate the levels of plasma adipokines and inflammation and oxidative stress markers in overweight and normal weight PD patients. MATERIAL AND METHODS: Thirty PD patients (12 M, 18 F; mean age 57.3 ± 16.6 years) were examined and 23 healthy volunteers were included as a control group. The levels of high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, leptin, the leptin receptor, adiponectin, malondialdehyde/4-hydroxynonenal, oxidized low-density lipoprotein, carbonyl groups and asymmetric dimethylarginine (ADMA) were measured in both groups. The nutritional status of each patient was determined by albumin levels, BMI, percentage of body fat (%F), lean body mass (LBM) and the Subjective Global Assessment (SGA) score. The adequacy of dialysis was estimated by weekly Kt/V measurements. RESULTS: According to the seven-point SGA scores and the albumin levels, the nutrition status of 15 patients was good (6-7 points), while 15 patients were mildly malnourished (3-5 points). The concentrations of hsCRP, leptin and adiponectin were statistically higher in the PD group than in the control group (p < 0.05). Markers of oxidative stress and inflammation were also higher in the PD group. The adiponectin level was inversely correlated with %F and BMI (Spearman's R = -0.3, p ≤ 0.05) and positively correlated with hsCRP level (R = -0.4). The level of leptin was positively correlated with %F, BMI and LBM (R = 0.4, p ≤ 0.05). Patients with normal BMI values had lower leptin concentrations (50.2 vs 242.8 µg/l) and higher adiponectin levels (30.0 vs 20.3 µg/ml) than overweight patients. The statistical analysis indicated that there were no differences in oxidative stress, inflammation and ADMA concentration between the lean and overweight PD patients. CONCLUSION: The nutritional status of lean and overweight patients was comparable. Signs of malnutrition were detected in both groups. The severity of chronic inflammation and oxidative stress were not related to BMI in PD patients.