Adverse reactions and influencing factors in children with primary immunodeficiencies receiving intravenous immunglobulin replacement.

OBJECTIVES: We aimed to determine adverse reactions and influencing factors, within the scope of the number of patients and total infusions, in patients with primary immunodeficiencies receiving intravenous immunoglobulin (IVIG) replacement. MATERIALS AND METHODS: Children with primary immunodeficiencies receiving IVIG replacement in Izmir Dr Behcet Uz Children's Hospital, between June 2014 and June 2016, were included in our study. RESULTS: The total number of the patients receiving IVIG replacement was 145 (37 female, 108 male). The number of total IVIG infusions was 1214. Adverse reactions were observed in 44.8% of the patients and 14.2% of the infusions. Common variable immunodeficiency was the most common diagnosis of the patients and adverse reactions most commonly developed in this group (24.2%). In all infusions the most frequent adverse reaction was headache (7.8%); fever was the most frequent immediate side effect (3.9%), whereas headache was the most common delayed adverse effect (5.1%). By logistic regression analyses, history of adverse reaction to IVIG in previous infusions, existence of concomitant infectious disease, past or family history of atopic disease, to receive IVIG infusion at the first time, or being under 10 years old were found associated with adverse reactions. There was no correlation between the concentration of IVIG preparations and the rate of side-effect development. CONCLUSIONS: In our study no severe adverse reaction to IVIG was observed, but many mild or moderate side effects occurred. Therefore, IVIG indications must be well identified. Patients, family of the patients and health care workers must be informed for adverse reactions.

TRPV2 POLYMORPHISMS INCREASE OR REDUCE THE RISK OF TYPE 2 DIABETES - HASHIMOTO THYROIDITIS COMORBIDITY.

CONTEXT: Thyroid disorders are common in diabetics and related to severe diabetic complications. TRPV2 ion channels have crucial functions in insulin secretion and glucose metabolism which have an important role in the pathophysiology of diabetes. Also, they have a significant effect on various immunological events that are involved in the HT pathophysiology. OBJECTIVE: This study aimed to investigate rs14039 and rs4792742 polymorphisms of the TRPV2 ion channels in type 2 diabetes mellitus (T2DM, n=100) Hashimoto thyroiditis (HT, n=70) and comorbid T2DM and HT (T2DM+HT, n=100) patients and control (n=100). DESIGN: Case-control study. SUBJECT AND METHODS: RT-PCR genotyping was used to determine rs14039 and rs4792742 polymorphisms with DNA samples of subjects and appropriate primer and probes. Besides, required biochemical analyses were performed. RESULTS: It was determined that the frequencies of the rs14039 GG homozygote polymorphic genotype and the G allele were significantly higher in T2DM+HT patients compared to the control (p=0.03 and p=0.01, respectively) and that especially the GG genotype increases the risk of T2DM+HT 3.046-fold (p=0.01, OR=3.046). It was detected that the GG genotype increased the risk of HT 2.54-fold (p=0.05, OR=2.541). TRPV2 rs4792742 polymorphisms reduce the risk of HT and T2DM+HT comorbidity almost by half and have a protective effect against HT and T2DM+HT. CONCLUSION: The rs14039 GG genotype of the TRPV2 gene significantly increases the risks of development of T2DM+HT and HT disorders, may have a significant role in the pathophysiology of these diseases, also leading to predisposition for their development. Conversely, rs4792742 polymorphic genotypes have a strong protective effect against the HT and T2DM+HT comorbidity.

Does atopy affect the course of viral pneumonia?

BACKGROUND: The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. METHODS: Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild-moderate and severe according to the course of pneumonia. Presence of atopy was evaluated with skin prick tests. Groups were compared to evaluate the risk factors associated with severe viral pneumonia. RESULTS: A total of 280 patients from nine centres were included in the study. Of these patients, 163 (58.2%) were male. Respiratory syncytial virus (29.7%), Influenza A (20.5%), rhinovirus (18.9%), adenovirus (10%), human metapneumovirus (8%), parainfluenza (5.2%), coronavirus (6%), and bocavirus (1.6%) were isolated from respiratory samples. Eighty-five (30.4%) children had severe pneumonia. Atopic sensitisation was found in 21.4% of the patients. Ever wheezing (RR: 1.6, 95% CI: 1.1-2.4), parental asthma (RR: 1.5, 95% CI: 1.1-2.2), other allergic diseases in the family (RR: 1.8, 95% CI: 1.2-2.9) and environmental tobacco smoke (RR: 1.6, 95% CI: 1.1-3.5) were more common in the severe pneumonia group. CONCLUSIONS: When patients with mild-moderate pneumonia were compared to patients with severe pneumonia, frequency of atopy was not different between the two groups. However, parental asthma, ever wheezing and environmental tobacco smoke exposure are risk factors for severe viral pneumonia in children.

Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo.

AIMS: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. METHODS AND RESULTS: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). CONCLUSION: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing.

Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis.

RATIONALE: The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis. OBJECTIVE: This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes. METHODS AND RESULTS: We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte-mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504±263 versus 194±77 fluorescence intensities in hearts; P=0.002). CONCLUSIONS: Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention.

Daily life reflections of acromegaly guidelines.

PURPOSE: To determine the differences in acromegaly diagnosis, treatment, and follow-up among Turkish endocrinologists, and to investigate how the published guidelines are applied in clinical practice. METHODS: The questionnaire was formatted as an electronic survey, conducted between November and December 2015, and sent weekly for 6 weeks via e-mail to 528 endocrinologists in Turkey. RESULTS: The questionnaire was answered by 37.4 % of endocrinologists. Insulin-like growth factor-1 and nadir growth hormone level after 75 g oral glucose tolerance test (nadir GH-OGTT) were the most commonly preferred methods for the initial diagnosis. A total of 49.5 % of the participants reported using preoperative medical therapy (MT) either routinely or on a case-to-case basis. Somatostatin analogs were the most commonly used drugs, both in pre- and postoperative MT. Disease activity following surgery was assessed in the 3rd postoperative month using IGF-1 levels. Similarly, IGF-1 monitoring was preferred in the follow-up period. Monitoring nadir GH-OGTT levels was the most commonly used method in the assessment of discordant test results. The dose titration was done at month 3 after the start of MT. Resistance to SRLs was considered after using the maximal dose for at least 6 months. Pegvisomant was generally used in second- and third-line therapy. Similarly, cabergoline was not preferred in monotherapy by the majority of participants. Radiotherapy was considered in patients with incomplete response to surgery and medical treatments. CONCLUSIONS: Although there were subtle differences, clinical practice guidelines were usually followed among Turkish endocrinologists.

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.

Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.

Tolerance development in food protein-induced allergic proctocolitis: Single centre experience.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is characterised by inflammation of the distal colon in response to one or more food proteins. It is a benign condition of bloody stools in a well-appearing infant, with usual onset between one and four weeks of age. OBJECTIVE: Our objective was to examine the clinical properties of patients with FPIAP, tolerance development time as well as the risk factors that affect tolerance development. METHODS: The clinical symptoms, offending factors, laboratory findings, methods used in the diagnosis and tolerance development for 77 patients followed in the Paediatric Allergy and Gastroenterology Clinics with the diagnosis of FPIAP during January 2010-January 2015 were examined in our retrospective cross-sectional study. RESULTS: The starting age of the symptoms was 3.3±4.7 months (0-36). Milk was found as the offending substance for 78% of the patients, milk and egg for 13% and egg for 5%. Mean tolerance development time of the patients was 14.7±11.9 months (3-66 months). Tolerance developed before the age of one year in 40% of the patients. Tolerance developed between the age of 1-2 years in 27%, between the age of 2-3 years in 9% and after the age of 3 years in 5% of the patients. CONCLUSIONS: Smaller onset age and onset of symptoms during breastfeeding were found associated with early tolerance development. In the majority of the patients, FPIAP resolves before the age of one year, however in some of the patients this duration may be much longer.

Diagnostic values for egg white specific IgE levels with the skin prick test in Turkish children with egg white allergy.

BACKGROUND: The diagnostic values for the skin prick test (SPT) diameters and egg white-specific IgE (EW-sIgE) levels that will allow us to predict the result of the oral food challenge test (OFC) in the diagnosis of egg white allergy vary by the community where the study is carried out. OBJECTIVE: This study aimed to determine the diagnostic values of SPT and EW-sIgE levels in the diagnosis of egg white allergy. METHODS: 59 patients followed with the diagnosis of egg allergy September 2013 to September 2015 were included in our retrospective cross-sectional study. The patients were investigated in terms of egg and anaphylaxis history or the requirement of the OFC positivity. The demographic, clinical and laboratory findings of the cases were recorded, and they were compared with the patients with the suspected egg allergy but negative OFC (n=47). RESULTS: In the study, for all age groups, the value of 5mm in SPT was found to be significant at 96.4% positive predictive value (PPV) and 97.8% specificity and the value of 5.27kU/L for EW-sIgE was found to be significant at 76% PPV and 86.6% specificity for egg white. The diagnostic power of the SPT for egg white (AUC: 72.2%) was determined to be significantly higher compared to the diagnostic power of the EW-sIgE (AUC: 52.3%) (p<0.05). CONCLUSION: Along with the determination of the diagnostic values of communities, the rapid and accurate diagnosis of the children with a food allergy will be ensured, and the patient follow-up will be made easier.

Effects of sacral neuromodulation on isolated urinary bladder function in a rat model of spinal cord injury.

INTRODUCTION: Sacral neuromodulation has been considered as an effective treatment option for various types of chronic voiding dysfunction, but the mechanism of action has not been well understood. The aim of this study was to evaluate the effect of chronic sacral neuromodulation on isolated bladder functions in a rat model of spinal cord injury. MATERIALS AND METHODS: Female Sprague-Dawley rats (250-300 g; N = 20) were assigned to four groups as follows: 1) control group (N = 6); 2) spinal cord transection group (SCT; N = 5); 3) spinal cord transection + sacral neuromodulation group (SCT + SNM; N = 5); 4) sham (spinal cord transection + electrode wire implantation without sacral neuromodulation; N = 4). The rats in the SCT, SCT + SNM, and sham groups were anesthetized with ketamine (60 mg/kg, i.p.) and xylazine (7 mg/kg, i.p.). The spinal cord was completely transected at T8-T9 level in SCT and SCT + SNM groups. Electrode wires were implanted into S3 dorsal foramina in both sham and SNM groups, but only the SNM group was subjected to electrical stimulation for four hours a day for three weeks. Twenty-one days later, the rats were sacrificed via anesthetic overdose, and isolated longitudinal bladder strip preparations were placed in organ baths for the investigation of their isometric responses to pharmacological agents. RESULTS: In isometric contraction experiments, SCT was found to increase the contraction responses of the bladder strips to muscarinic stimulation, and SNM could not prevent this increase. In isometric relaxation experiments, SCT caused a decrease in ß-adrenergic relaxation responses, and SNM augmented the bladder's ß-adrenergic relaxation responses. Nitric oxide did not affect the relaxation responses. CONCLUSION: In our rat model of SCT, SNM seemed to alter adrenergic receptor function in the urinary bladder. Further studies are required to clarify the mechanism of these alterations at the level of bladder receptors following sacral neuromodulation.

beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration.

CONTEXT: Propranolol, atenolol, and ICI118,551 are non-selective ß-adrenergic receptor (AR), ß1-AR, and ß2-AR antagonists, respectively. OBJECTIVE: We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells. MATERIALS AND METHODS: ß-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration. RESULTS AND DISCUSSION: All cell lines expressed ß-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective ß-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications. CONCLUSION: Beta2-AR antagonist seemed to be the most cytotoxic ß-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, ß2-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective ß-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.

Automated blood volume estimation in surgical drains for clinical decision support.

OBJECTIVE: Monitoring Jackson Pratt and Hemovac drains plays a crucial role in assessing a patient's recovery and identifying potential postoperative complications. Accurate and regular monitoring of the blood volume in the drain is essential for making decisions about patient care. However, transferring blood to a measuring cup and recording it is a challenging task for both patients and doctors, exposing them to bloodborne pathogens such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). To automate the recording process with a non-contact approach, we propose an innovative approach that utilizes deep learning techniques to detect a drain in a photograph, compute the blood level in the drain, estimate the blood volume, and display the results on both web and mobile interfaces. MATERIALS AND METHODS: Our system employs semantic segmentation on images taken with mobile phones to effectively isolate the blood-filled portion of the drain from the rest of the image and compute the blood volume. These results are then sent to mobile and web applications for convenient access. To validate the accuracy and effectiveness of our system, we collected the Drain Dataset, which consists of 1,004 images taken under various background and lighting conditions. RESULTS: With an average error rate of less than 5% in milliliters, our proposed approach achieves highly accurate blood level detection and estimation, as demonstrated by our trials on this dataset. The system also exhibits robustness to variations in lighting conditions and drain shapes, ensuring its applicability in different clinical scenarios. CONCLUSIONS: The proposed automated blood volume estimation system can significantly reduce the time and effort required for manual measurements, enabling healthcare professionals to focus on other critical tasks. The dataset and annotations are available at: https://www.kaggle.com/datasets/ayenahin/liquid-volume-detection-from-drain-images and the code for the web application is available at https://github.com/itsjustaplant/AwesomeProject.git.

Effect of hyperbaric oxygen in hepatopulmonary syndrome: an innovative experimental study.

OBJECTIVE: This study aimed to analyze the effect of hyperbaric oxygen treatment (HBOT) in hepatopulmonary syndrome (HPS). MATERIALS AND METHODS: Five-month-old female Wistar-Albino rats were randomly divided into three groups: Group I, the control group; Group II, the cirrhosis group; and Group III, the cirrhosis group + HBOT group. Rats were exposed to HBO sessions (2.4 atm./60 min) for 20 days. Animals were sacrificed 24 hours after the last HBO session. Biochemical analysis, oxygenation parameters, NO and NO synthase (NOS) levels, histopathological changes in the liver and lungs, and pulmonary artery diameter were measured. RESULTS: A total of 24 rats (10 rats were included in Group I, six rats in Group II, and eight rats in Group III) weighing 220-250 g were included in the study. Significant differences were observed for NO and NOS (9.10±1.05 to 12.17±1.85 µmol/L, p<0.05 and 0.46±0.31 to 1.17±0.39 U/ml, p<0.05, respectively) at baseline and day 36 only in group II. Inflammatory cell infiltration and bronchial injury were significantly increased in group II compared to group I (p=0.007 and p=0.008, respectively) but not in group III (p=0.266 and p=0.275, respectively). Pulmonary artery diameter was significantly lower in group III compared with group II at all sites in both lungs (p<0.05). CONCLUSIONS: HBOT may be a promising treatment for HPS by reducing NO and NOS activity, perialveolar arteriolar dilation, lung inflammation, and injury and guiding future clinical trials.

The effect of long-term oral tadalafil treatment on corpus cavernosum function in an experimental spinal cord transection rat model.

OBJECTIVES: The aim of this study was to investigate the pharmacological effects of long-term oral tadalafil treatment on the corpus cavernosum function in rats subjected to experimental spinal cord transection (SCT). METHODS: Thirty young adult, male Sprague­Dawley rats were randomly divided into five groups (n» 6, each), as follows: (1) Control,(2) Control surgery (Sham), (3) Tadalafil (Td), (4) Experimental SCT, and (5) SCT + Tadalafil (SCT + Td). SCT rat model: after removal of T8-T9 spinal processes and laminates, a full-thickness scalpel incision was made in the spinal cord. SCT + Td rat model:rats subjected to SCT were given tadalafil (5mg kg(-1), p.o.) for 4 weeks. Next, the penile cavernous tissues obtained by en blocexcision were trimmed free of the surrounding tissue to isolate cavernosal smooth muscle strips, which were then transferred into the isolated organ baths to investigate isometric tension changes in response to various bioactive agents and electrical field stimulation (EFS). RESULTS: The relaxation response to acetylcholine at 0.01 mM concentration was significantly less in the SCT group compared with other groups. EFS-induced relaxation in the basal and precontracted cavernous tissue preparations was greater in the SCT + Td group than in the SCT group. CONCLUSION: This study demonstrated that long-term tadalafil administration preserves relaxation responses probably by affecting through the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in SCT-applied rats. This treatment strategy might preserve the erectile process and prevent the SCT-induced permanent damage in the cavernosal tissue.

A QSAR study to predict the survival motor neuron promoter activity of candidate diaminoquinazoline derivatives for the potential treatment of spinal muscular atrophy.

Spinal Muscular Atrophy is a genetic neuromuscular disease that leads to muscle weakness and atrophy and it is characterized by the loss of α-motor neurons in the spinal cord's anterior horn cells. The disease appears due to low levels of the survival motor neuron protein. There are continuing clinical trials for the treatment of Spinal Muscular Atrophy. Quinazoline-based compounds are promising since they were tested on fibroblasts derived from the patients and found to increase the survival motor neuron protein levels. In this study, using multiple linear regression, we generated robust and valid quantitative structure- activity relationship models to predict the survival motor neuron-2 promoter activity of the new candidate compounds using the experimental survival motor neuron-2 promoter activity values of 2,4-diaminoquinazoline derivatives taken from the literature. The novel compounds designed by combining the pyrido[1,2-α]pyrimidin-4-one moeity of the known drug Risdiplam with that of 2,4 - diaminoquinazoline scaffold were predicted to exhibit strong promoter activities.

Effect of hydrogen sulfide on ischemia-reperfusion injury of kidney: A systematic review and meta-analysis of in vivo animal studies.

Hydrogen sulfide (H2S) has been shown to be effective against kidney ischemia-reperfusion injury (IRI) in animal studies. We aimed to evaluate the current evidence from in vivo animal studies for the protective effects of H2S against kidney IRI by systematically reviewing the literature and performing a meta-analysis. Based on the preregistered protocol (PROSPERO: CRD42021295469); PubMed, Medline, Embase, Web of Science, and Scopus were searched to identify in vivo animal studies evaluating the effect of H2S against kidney IRI. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated and pooled using random-effects meta-analysis. Twenty-two articles complied with eligibility criteria, from which the creatinine levels of 152 control animals and 182 animals treated with H2S from 27 individual experiments were pooled. H2S treatment significantly decreased serum creatinine (SMD = -1.82 [95% CI -1.12, -2.51], p < 0.0001), blood urea nitrogen (-2.50 [-1.46, -3.54], p < 0.0001), tissue malondialdehyde (-2.59 [-3.30, -1.88], p < 0.0001), tunel positive cells (-3.16 [-4.38, -1.94], p < 0.0001), and tubular damage score (-2.01 [-3.03, -0.99], p < 0.0001). There was a high heterogeneity across studies (I2 = 83.5% for serum creatinine level). In meta-regression analysis, the type of H2S donor and its application time accounted for 11.3% (p = 0.025) and 16.6% (p = 0.039) of heterogeneity, respectively. Accordingly, H2S protects the kidney against IRI only if it is given as GYY4137 before or during ischemia. Although H2S is a potential candidate against kidney IRI, further well-designed preclinical studies focusing on GYY4137 are warranted before clinical implication.

Development of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors glow and destroy.

Drug resistant and undetectable tumors easily escape treatment leading metastases and/or recurrence of the lethal disease. Therefore, it is vital to diagnose and destroy micro tumors using simple yet novel approaches. Here, we present fluorescence-based detection and light-based destruction of cancer cells that are known to be resistant to standard therapies. We developed a superparamagnetic iron oxide nanoparticle (SPION)-based theranostic agent that is composed of self-quenching light activated photosensitizer (BPD) and EGFR targeting ligand (Anti-EGFR ScFv or GE11 peptide). Photosensitizer (BPD) was immobilized to PEG-PEI modified SPION with acid-labile linker. Prior to stimulation of the theranostic system by light its accumulation within cancer cells is vital since BPD phototoxicity and fluorescence is activated by lysosomal proteolysis. As BPD is cleaved, the system switches from off to on position which triggers imaging and therapy. Targeting, therapeutic and diagnostic features of the theranostic system were evaluated in high and moderate level EGFR expressing pancreatic cancer cell lines. Our results indicate that the system distinguishes high and moderate EGFR expression levels and yields up to 4.3-fold increase in intracellular fluorescence intensity. Amplification of fluorescence signal was as low as 1.3-fold in the moderate or no EGFR expressing cell lines. Anti-EGFR ScFv targeted SPION caused nearly 2-fold higher cell death via apoptosis in high EGFR expressing Panc-1 cell line. The developed system, possessing advanced targeting, enhanced imaging and effective therapeutic features, is a promising candidate for multi-mode detection and destruction of residual drug-resistant cancer cells.

How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups.

INTRODUCTION: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. OBJECTIVE: To explore the current management of the native kidney masses in KT patients. ACQUISITION OF EVIDENCE: We performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. SYNTHESIS OF EVIDENCE: In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. CONCLUSIONS: Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Stimuli-responsive theranostic system: A promising approach for augmented multimodal imaging and efficient drug release.

Destruction of drug resistant and invisible micro-tumors requires innovative screening and treatment modalities. Theranostic nanosystems offering multimodal imaging and therapy are attractive platforms with potential to make micro-tumors visible to clinicians. Gold nanoparticles (AuNPs) are intrinsic theranostic agents and act as fluorescence quenchers. They can be easily transformed to multimodal imaging and combination therapy agents by combining them with various adjuvant therapies such as photodynamic therapy. In this study, we developed a highly specific, hybrid theranostic agent that is only activated when it meets with its stimuli at the site of interest. Surface-coated AuNPs were modified with Cathepsin B cleavable peptide (stimuli responsive linker) and Verteporfin (photosensitizer and fluorescence imaging agent). Unless the theranostic system meets with the internal stimuli in tumor cells, fluorescence is quenched due to AuNP-Verteporfin and Verteporfin-Verteporfin interactions. Following cellular internalization of the theranostic agent, fluorescence is gained by Cathepsin B cleavage and phototoxicity is initiated by light. The system was efficiently internalized by SKOV-3 cells and demonstrated high specificity towards its stimuli. In comparison to Verteporfin, ∼14-fold fluorescence increase, 81% fluorescence recovery and comparable toxicity were achieved. The system is a promising candidate for multimodal imaging and dual treatment to destroy the micro-tumors.

Near-IR single fluorophore quenching system based on phthalocyanine (Pc) aggregation and its application for monitoring inhibitor/activator action on a therapeutic target: L1-EN.

Controlled H-aggregation of single Pc-labeled oligonucleotides is utilized as a fluorescence quenching system to discern changes in enzyme activity for the discovery of inhibitors for Long Interspersed Element 1 endonuclease (L1-EN), which is involved in genome instability and implicated in many different diseases.