Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications.

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.

Computational Insights on the Hydride and Proton Transfer Mechanisms of D-Arginine Dehydrogenase.

D-Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is an amine oxidase which catalyzes the conversion of D-arginine into iminoarginine. It contains a non-covalent FAD cofactor that is involved in the oxidation mechanism. Based on substrate, solvent, and multiple kinetic isotope effects studies, a stepwise hydride transfer mechanism is proposed. It was shown that D-arginine binds to the active site of enzyme as α-amino group protonated, and it is deprotonated before a hydride ion is transferred from its α-C to FAD. Based on a mutagenesis study, it was concluded that a water molecule is the most likely catalytic base responsible from the deprotonation of α-amino group. In this study, we formulated computational models based on ONIOM method to elucidate the oxidation mechanism of D-arginine into iminoarginine using the crystal structure of enzyme complexed with iminoarginine. The calculations showed that Arg222, Arg305, Tyr249, Glu87, His 48, and two active site water molecules play key roles in binding and catalysis. Model systems showed that the deprotonation step occurs prior to hydride transfer step, and active site water molecule(s) may have participated in the deprotonation process.

Association between RS Time in Electrocardiogram and Right Ventricular Functions in Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: The occurrence of right ventricular (RV) dysfunction in chronic obstructive pulmonary disease (COPD) results in an increased risk of mortality. We aimed to study the diagnostic value of RS time in the recognition of COPD patients with RV dysfunction. METHODS: 120 consecutive COPD patients were divided into two groups, patients with and without RV dysfunction, and compared them in terms of parameters including RS time. RS time was defined as the longest interval from the beginning of the QRS complex to the nadir of the S- or S'-wave in the inferolateral leads on an electrocardiogram. RESULTS: RV dysfunction was observed in 36% of consecutive COPD patients with a mean age of 63.4 ± 9.8 years (83.3% male) and a mean forced expiratory volume in 1 s of 1.51 ± 0.62 lt. The heart rate, right QRS axis deviation frequency, S1S2S3 pattern frequency, and RS time (p < 0.01) were significantly higher in the patients with RV dysfunction than in those without. Body surface area, heart rate, and RS time (p < 0.001) were independent predictors of an RV dysfunction. An ROC analysis showed that the best RS time cutoff value for the prediction of RV dysfunction was 60 ms with a sensitivity of 81.4% and a specificity of 74.0%. CONCLUSION: In patients with COPD, RS time prolongation, which can be easily and quickly determined from the electrocardiogram, may be a marker for RV dysfunction.

Tailored total neoadjuvant therapy for locally advanced rectal cancer: One size may not fit for all!

While current neoadjuvant protocols have proven benefits on local control for majority of patients with locally advanced rectal cancer, there are certain clinical conditions that require future advances for improving the outcomes. Total neoadjuvant therapy incorporates systemic chemotherapy planned within standard neoadjuvant protocols either before or after radiotherapy for locally advanced rectal cancer as a whole. Enhanced compliance with planned oncological therapy, tumour downstaging, administration of chemotherapy at the earliest time in the disease course to help assessing chemosensitivity are the proposed benefits of total neoadjuvant therapy in patients with locally advanced rectal cancer. Patient selection criteria for administration of total neoadjuvant therapy in the recent guidelines are unclear. Since current literature is inconclusive for the optimal sequence and type of radiotherapy and chemotherapy, premature incorporation of total neoadjuvant therapy for all locally advanced rectal cancers may result in overtreatment and subsequently toxicity. This article aims to discuss the current literature and to propose a future perspective by considering real-life scenarios reflecting patients' needs for treatment of locally advanced rectal cancer.

Effects of cordierite particulate filters on diesel engine exhaust emissions in terms of pollution prevention approaches for better environmental management.

In this study, a specific diesel fuel is experimentally tested in a 4-cylindered diesel engine with and without a cordierite-based diesel particulate filter (CPF) to show the prevention of emissions by using an after treatment system (ATS). In this context, engine exhaust emissions, total particle concentration (TPC) and soot concentration are investigated. The diesel engine is firstly evaluated with the data directly measured from the engine output (DEO) (without after treatment option), and then the changes in the exhaust emission are examined by using an ATS which is a cordierite-based diesel particulate filter to prevent pollution. In this regard, total particle concentration of DEO option is found to be 6134041.20 1/cm3 and total particle concentration by using CPF is obtained to be 707.84 1/cm3. 99.99% reduction in TPC is achieved thanks to the use of CPF. The soot concentration of DEO option is calculated to be 2.158 mg/m3. However, the soot concentration is found to be 0.014 mg/m3 by using the CPF. The particulate matters are burned at high temperatures after being filtered at the exhaust output thanks to the regeneration process within the CPF after treatment. CO emissions decreased from 0.7489 g/kWh to 0.7273 g/kWh with the CPF utilization, while HC emissions decreased from 0.0965 g/kWh to 0.0900 g/kWh via CPF. However, an increase in CO2 and NOx emissions are observed due to oxidation in the CPF.

P Wave Peak Time for Predicting an Increased Left Atrial Volume Index in Hemodialysis Patients.

OBJECTIVE: An increased left atrial volume index (LAVI) is related to increased mortality in hemodialysis patients. In the present study, we evaluated the association between the LAVI and the P wave peak time (PWPT), a newly introduced electrocardiographic parameter, in hemodialysis patients. METHODS: The study population was made up of 79 hemodialysis patients with a mean age of 53 ± 18 years (55.7% were males). These patients were divided into a normal LAVI (≤28 mL/m2) group (n = 45) and an increased LAVI (>28 mL/m2) group (n = 34). The demographic, clinical, laboratory, echocardiographic, and electrocardiographic variables of the groups were compared. RESULTS: The P wave terminal force from lead V1, P wave dispersion and PWPTs obtained from leads V1 and D2 (PWPTD2) were significantly higher in the patients with increased LAVIs. In multivariable analysis, only the PWPTD2was an independent predictor of an increased LAVI (odds ratio = 1.117, 95% CI = 1.052-1.185, p < 0.001). The receiver-operating characteristic curve analysis showed that the best PWPTD2 cutoff value for predicting an increased LAVI was 60 ms, with a sensitivity of 76.5% and a specificity of 66.7% (area under the curve = 0.736, 95% CI = 0.625-0.829, p < 0.001). CONCLUSION: This study showed that a prolonged PWPTD2 was independently associated with an increased LAVI in hemodialysis patients. Therefore, measuring the PWPTD2 duration on an electrocardiogram may help define high-risk hemodialysis patients with increased LAVIs.

The Association of Fractional Pulse Pressure with Acute Kidney Injury in Patients Undergoing Coronary Intervention due to ST-Segment Elevated Myocardial Infarction.

OBJECTIVE: Acute kidney injury (AKI), which is prevalent in ST-segment elevated myocardial infarction (STEMI) patients who have undergone primary percutaneous coronary intervention (PCI), is associated with poor cardiovascular outcomes. As high pulse pressure (PP) is associated with adverse cardiovascular events, the present study's aim was to evaluate the relationship between fractional PP (PPf) and AKI in patients with STEMI who underwent primary PCI. SUBJECTS AND METHODS: All laboratory findings as well as echocardiographic and angiographic data of 1,170 consecutive STEMI patients were retrospectively screened. PPf was calculated from the pressures invasively measured after sheath insertion and before performing coronary angiography. RESULTS: From 1,170 eligible STEMI patients (mean age 56 years, 18.2% female), AKI developed in 143 (12.2%) patients. The PPf and pulsatility index were significantly higher in patients with AKI than those without (0.53 ± 0.10 vs. 0.61 ± 0.10, p < 0.001, and 0.80 ± 0.03 vs. 0.82 ± 0.03, p < 0.001, respectively). PPf was also found to be associated with AKI in univariable (OR 2.183, 95% CI 1.823-2.614, p< 0.001) and multivariable (OR 1.874, 95% CI 1.513-2.322, p < 0.001) analysis. In-hospital mortality was higher in patients with AKI than those without. CONCLUSION: Invasively measured PPf, which can be easily measured and has no additional cost in STEMI patients undergoing coronary intervention, is an independent predictor of AKI. In addition, PPf is superior to other blood pressure values and derivatives in AKI prediction.

Molecular characterization of Blastocystis in cattle in Turkey.

Blastocystis genus exist in a wide variety of hosts, including humans, birds, insects, annelids, amphibians, fish, and mammals. PCR-based molecular diagnostic methods have been successfully used to detect Blastocystis spp. in feces, and small subunit ribosomal ribonucleic acid (SSU rRNA) gene-based subtyping is the preferred method for diagnosis. There has been discussion about the subtypes of Blastocystis spp. which has been detected so far. To date, 26 different subtypes have been reported. The aim of this study was to determine the existence and diversity of Blastocystis spp. in cattle. In our study, a total of 80 stool samples were collected from cows and calves at 13 different farms in Burdur and one farm in Aydin. Using molecular method, a total of 9 samples out of 80 samples were found to be positive (11.25%) for Blastocystis. As a result of sequence analysis of Blastocystis positive samples, the subtype 14 was detected on seven samples, while in the other two samples, Blastocystis subtype 10 was identified. The ST10 and ST14 subtypes are commonly reported in animals but not isolated from human. Our analyses showed genetic differences among Blastocystis subtypes. Our study is the first Blastocystis subtyping study from cattle in Turkey.

Environmental pollution cost analyses of biodiesel and diesel fuels for a diesel engine.

In this study, Japanese Industrial Standard diesel no 2 and waste cooking oil biodiesel fuels are compared in terms of environmental pollution cost analysis. The experiments of the diesel and biodiesel fueled diesel engine are done at 100 Nm, 200 Nm and full load (294 Nm), while engine speed is constant at 1800 rpm. The method used in this study consists of a combination of economic and environmental parameters. According to the analyses, the total environmental pollution cost of the biodiesel is higher than the diesel fuel. On the other hand, the total cost of the CO2 emissions of the diesel fuel is generally found to be higher than biodiesel fuel in terms of the life cycle based environmental pollution cost. The specific environmental pollution cost is found as minimum at full load to be 2.217 US cent/kWh for the diesel fuel and 2.449 US cent/kWh for the biodiesel fuel at full load. On the other hand, the life cycle based specific environmental pollution cost is determined as minimum at full load to be 5.050 US cent/kWh for the diesel fuel and 5.309 US cent/kWh for the biodiesel fuel. The biodiesel fuel has higher values than diesel fuel in terms of the specific environmental pollution cost rates. The maximum total carbon dioxide emission rate is found as 0.2405 × 10-3 kg/kJ for the biodiesel fuel at 100 Nm engine torque and the minimum one is obtained as 0.1884 × 10-3 kg/kJ for the diesel fuel at full load. When the payback periods of the fuels are examined, biodiesel has longer period than diesel. The environmental payback period and life cycle based environmental payback period are also compared for fuels. In this context, the biodiesel has longer environmental payback periods rates than diesel. Consequently, the biodiesel fueled engine has higher environmental pollution cost rates than the diesel fueled engine, while the total carbon dioxide parameter of the diesel fuel is close to the biodiesel fuel's rate. Also, all of the other environmental parameters of diesel fuel is generally better than biodiesel. Consequently, the diesel fuel is generally better option than the biodiesel considering environmental aspects. For better environmental management, the diesel fuel utilization in the diesel engine is slightly better option than biodiesel fuel in terms of environmental pollution cost analysis.

Relation between aortic knob width and subclinical left ventricular dysfunction in hypertensive patients.

BACKGROUND: The assessment of left ventricular (LV) structure and function is important in the evaluation of hypertensive heart disease, as it provides information on the cardiovascular morbidity and mortality. Aortic knob width (AKW) is a measurement of radiographic structure formed by the foreshortened aortic arch and a portion of the descending aorta. The main aim of this study was to investigate the relation between AKW on the routine chest radiography and subclinical LV dysfunction in hypertensive patients. PATIENTS AND METHODS: A total of 144 patients with hypertension admitted to the cardiology outpatients clinic were enrolled consecutively. The patients were divided into two groups according to tissue Doppler-derived myocardial performance index (MPI): subclinical LV dysfunction group (abnormal MPI ≥ 0.5, n = 85) and absence of subclinical LV dysfunction group (normal MPI< 0.5, n = 59). RESULTS: Patients with subclinical LV dysfunction were older (60 ± 8 vs. 54 ± 8, p = 0.001). Left ventricular mass index (LVMI) (96 ± 27 vs. 74 ± 24, p < 0.001) and prevalence of LV hypertrophy (28 vs. 8%, p = 0.011) were significantly different between two groups. Patients with subclinical LV dysfunction had higher AKW (42 ± 6 vs. 34 ± 5, p < 0.001) compared with patients without subclinical LV dysfunction. There was a significant correlation between MPI and AKW (r = 0.7, p < 0.001). Multiple logistic regression analysis showed that AKW (ß = 0.617, p = 0.001) and posterior wall thickness (PWth) (ß = 1.189, p = 0.021) were independently associated with subclinical LV dysfunction. Analysis using the Receiver Operating Characteristic (ROC) curve has demonstrated that aortic knob of 37 mm constitutes the cutoff value for the presence of subclinical LV dysfunction with 85.9% sensitivity and 86.4% specificity (The Area under the Curve ± Standard Error (AUC±SE) = 0.916 ± 0.024, p < 0.001). CONCLUSION: AKW may provide important predictive information on subclinical LV dysfunction in patients with hypertension.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

BACKGROUND: There are insufficient predictive markers for renal cell carcinoma (RCC). METHODS: A total of 308 metastatic RCC patients were analyzed retrospectively. RESULTS: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. CONCLUSIONS: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Association among tenascin-C and NT-proBNP levels and arrhythmia prevalence in heart failure.

PURPOSE: Tenascin-C (TN-C) and amino-terminal fragment of the B-type natriuretic peptide (NT-proBNP) are the important predictors in prognosis of heart failure (HF). The aim of this study was to analyze the relationship of TN-C and NT-proBNP levels with the frequency and severity of ventricular arrhythmia. MATERIALS AND METHODS: Our study included 107 HF patients with EF < 45%. According to Holter analysis, the patients were divided into two groups as malignant arrhythmia group (n=29) with Lown Class 4a and 4b arrhythmia and benign arrhythmia group(n=78) with Lown Class 0-3b arrhythmia. The groups were compared with respect to levels of TN-C and NT-proBNP. The relationship of TN-C and NT-proBNP levels with frequency of ventricular premature beat (VPB) was also analyzed. FINDINGS: NT-proBNP (5042.1±1626 versus 1417.1±1711.6 pg/ml) and TN-C (1089±348.6 versus 758.5±423.9 ng/ml) levels were significantly higher in the malignant arrhythmia group than that of the benign arrhythmia group (p.

Outcome of Patients With Metastatic Chromophobe Renal Cell Carcinoma Treated With Sunitinib.

BACKGROUND: Sunitinib is a standard treatment for metastatic clear cell renal cell carcinoma (mccRCC). Data on its activity in the rare variant of metastatic chromophobe renal cell carcinoma (mchRCC), are limited. We aimed to analyze the activity of sunitinib in a relatively large and homogenous international cohort of mchRCC patients in terms of outcome and comparison with mccRCC. METHODS: Records from mchRCC patients treated with first-line sunitinib in 10 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC patients were individually matched to mccRCC patients. We compared the clinical benefit rate, progression-free survival (PFS), and overall survival (OS) between the groups. RESULTS: Between 2004 and 2014, 36 patients (median age, 64 years; 47% male) with mchRCC were treated with first-line sunitinib. Seventy-eight percent achieved a clinical benefit (partial response + stable disease). Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the Heng risk (hazard ratio [HR], 3.3; p = .03) and pretreatment neutrophil-to-lymphocyte ratio (NLR) >3 (HR, 0.63; p = .02). Factors associated with OS were the Heng risk (HR, 4.1; p = .04), liver metastases (HR, 3.8; p = .03), and pretreatment NLR <3 (HR, 0.55; p = .03). Treatment outcome was not significantly different between mchRCC patients and individually matched mccRCC patients. In mccRCC patients (p value versus mchRCC), 72% achieved a clinical benefit (p = .4) and median PFS and OS were 9 (p = .6) and 25 (p = .7) months, respectively. CONCLUSION: In metastatic chromophobe renal cell carcinoma, sunitinib therapy may be associated with similar outcome and toxicities as in metastatic clear cell renal cell carcinoma. The Heng risk and pretreatment NLR may be associated with PFS and OS. IMPLICATIONS FOR PRACTICE: Data on the activity of sunitinib in metastatic chromophobe renal cell carcinoma (mchRCC) are limited. This study analyzed the activity of sunitinib in a cohort of mchRCC patients. Of 36 patients with mchRCC who were treated with first-line sunitinib, 78% achieved a clinical benefit. Median PFS and OS were 10 and 26 months, respectively. Treatment outcome was not significantly different between mchRCC patients and individually matched metastatic clear cell RCC patients.

Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.

Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third cycle. In conclusion, the same schedule of chemotherapy may lead to different myelotoxicities in different types of cancer. These results should be taken into consideration in terms of supportive care and management of toxicity.

A DFT Approach to the Mechanistic Study of Hydrozone Hydrolysis.

Hydrazone chemistry is widely utilized in biomedical field as a means of bioconjugation protocol, especially in drug delivery field due to pH labile nature of this linkage. In the light of kinetics studies, the generally accepted mechanism for the hydrolysis of hydrazones involves two main steps, namely, nucleophilic addition of water molecule to the hydrazone molecule to form carbinolamine intermediate and subsequent decomposition of this intermediate into the hydrazine and aldehyde/ketone moieties. Hydrolysis of hydrazones is catalyzed in the acidic environments and is thought to proceed through several proton transfer steps. To the best of our knowledge, in the literature no detailed theoretical study has been reported related to the mechanism of hydrolysis. In this study, we evaluated the proposed mechanism with DFT calculations with M06-2X functional at the 6-311+g(d,p) level including conductor-like polarizable continuum model solvation model. We also analyzed possible proton transfer pathways and assessed energetics of each step.

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

BACKGROUND: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. METHODS: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. RESULTS: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. CONCLUSION: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients.

AIM OF THE STUDY: Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. MATERIAL AND METHODS: Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. RESULTS: Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. CONCLUSIONS: As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients.

Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma.

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

The increased transglutaminase 2 expression levels during initial tumorigenesis predict increased risk of metastasis and decreased disease-free and cancer-specific survivals in renal cell carcinoma.

PURPOSE: The aim of this study was to investigate the role of transglutaminase 2(TG2) in renal cell carcinoma (RCC) by comparing the immunohistochemistry staining of primary and metastatic tumor tissues. METHODS: A total of 33 metastatic RCC(mRCC) and 33 non-metastatic RCC (nmRCC) patients who were matched as closely as possible based on gender, age, nuclear grade and pathologic T stage were retrospectively investigated. TG2 immunohistochemistry staining was performed on paraffin-embedded primary tumor tissues from both patient groups and on metastatic tissues from mRCC patients. The tissues were scored from 0 to 7 according to the TG2 staining. Furthermore, the patients were stratified into two groups using median primary tumor staining score as the cutoff value: Group 1 (high risk, n = 41) and Group 2(low risk, n = 22). The clinical, histopathological and survival outcomes were compared between these risk groups using Chi-square test, t test, Mann-Whitney U test and Kaplan-Meier survival analyses. RESULTS: The median TG2 score for primary tumor was 5 for the entire study population. The median primary tumor TG2 score of the mRCC patients was significantly higher compared to the nmRCC patients (6 vs. 4, p < 0.001). The TG2 score between the primary and metastatic tissues of mRCC patients was not significantly different (6 vs. 7, p = 0.086). The percentage of metastatic patients was significantly higher in Group 1 compared to Group 2 (68.3 vs. 18.2 %, p < 0.001). Kaplan-Meier analyses showed that 5-year disease-free (34.9 vs. 92.9 %, p = 0.001) and cancer-specific (47.4 vs. 86.5 %, p = 0.04) survival rates were significantly lower in high-risk group. CONCLUSIONS: The increased expression of TG2 in primary tumor predicts metastasis in RCC patients and is also associated with a decrease in disease-free and cancer-specific survival outcomes.