The role of immunotherapy in urological cancers

Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials

Chromatin-modifying enzymes as modulators of reprogramming

Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming, the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatin-modifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors. © 2012 Macmillan Publishers Limited. All rights reserved

An overview of burst, buckling, durability and corrosion analysis of lightweight FRP composite pipes and their applicability

© 2019 Elsevier Ltd. All rights reserved.The main aim of this review article was to address the performance of filament wound fibre reinforced polymer (FRP) composite pipes and their critical properties, such as burst, buckling, durability and corrosion. The importance of process parameters concerning merits and demerits of the manufacturing methods was discussed for the better-quality performance. Burst analysis revealed that the winding angle of ±55° was observed to be optimum with minimum failure mechanisms, such as matrix cracking, whitening, leakage and fracture. The reduction of buckling effect was reported in case of lower hoop stress value in the hoop to axial stress ratio against axial, compression and torsion. A significant improvement in energy absorption was observed in the hybrid composite pipes with the effect of thermal treatment. However, the varying winding angle in FRP pipe fabrication was reported as an influencing factor affecting all the aforementioned properties. Almost 90% of the reviewed studies was done using E-glass/epoxy materials for the composite pipe production. By overcoming associated limitations, such as replacing synthetic materials, designing new material combinations and cost-benefit analysis, the production cost of the lightweight FRP composite pipes can be decreased for the real-time applications.Peer reviewe

Fractal dimensions of kappa-carrageenan gels during gelation and swelling

A photon scattering technique for research on the sol-gel and gel-sol transitions in kappa-carrageenan-water systems with various carrageenan contents (CC) was utilized for characterizing the fractal dimensions during gelation and swelling. It was observed that the scattered photon intensity, I-sc, increased at all temperatures with an increase in the CC when I-sc was monitored against temperature. Additionally, the sol-gel transition temperatures were found to be much lower than the gel-sol transition temperatures, causing hysteresis of the phase transition loops. I-sc increased with an increase in CC at all test temperatures, which is attributed to the formation of a fractal-like carrageenan gel. After drying, the gels were used in swelling experiments where the gels were immersed in water at room temperature, reswelling to the original structure. It was observed that I-sc from the carrageenan gels increased as the CC was increased. The fractal dimension, d, during gelation was found to increase as the gelation temperature was increased. On the other hand, the d values during swelling decreased as the swelling time was increased

Effects of GNP addition on optical properties and band gap energies of PMMA films

In this study, the effects of graphene nanoplatelet (GNP) doping on the optical parameters (absorption coefficient, alpha and extinction coefficient, k) and the optical transition energies (optical band gap and Urbach energies) of poly(methyl methacrylate)/graphene nanoplatelet (PMMA/GNP) composite films were studied. PMMA/GNP composite films with various GNP mass fractions were prepared by spin coating technique. The absorbance (A) changes of the prepared composites were measured by using UV-Vis technique. The alpha and k values of the composites were obtained from UV-Vis data. The observed rapid increase in A values in UV-region were associated with the optical transitions of GNP electrons from valence to conduction band. The direct (E-d) and indirect (E-i) optical band gap energies of the composites were determined by using Tauc method. Both of the band gap energies were decreased when the GNP content in the PMMA matrix is increased. The decrease in the band gap energies was interpreted as evidence of increased conductivity of the composites. Additionally, energies of the band tails (Urbach energy) were calculated. It was seen that the Urbach energy levels were increased with GNP content. POLYM. COMPOS., 40:1862-1869, 2019. (c) 2018 Society of Plastics Engineer

A comparison of fluorescence and UV-visible spectrometry techniques for thermal phase transitions of agarose gels

In this study, thermoreversible phase transitions of high (HMP) and low (LMP) melting point agarose gels were investigated by using the UV-vis and fluorescence spectroscopy techniques. Pyranine was added to the aqueous solution of agarose as a fluorescence-probe. Transmitted light (I (tr)) and fluorescence emission (I (fl)) intensities from the gel samples with different agarose concentrations were monitored during the heating (gel-sol) and cooling (sol-gel) processes. For the both techniques, gel-sol (T (gs)) and sol-gel (T (sg)) transition temperatures were determined from the first derivatives of the sigmoidal transition paths. It was observed that the critical transition temperatures obtained from UV-vis and fluorescence data slightly increased depending on the agarose type and concentration, and those values were found to be in accord with each other. Transition activation energies were determined using the Arrhenius type equation and were found to be strongly correlated with the agarose content in the gel system. The produced gel-sol (Delta E (gs)) and sol-gel (Delta E (sg)) transition energies from the fluorescence data were found to be lower than that of the UV-vis data, which was attributed to the temperature-dependent fluorescence quenching effect

Thermal Phase Transitions of Agarose in Various Compositions: A Fluorescence Study

The effect of agarose content on thermal phase transitions of the agarose gels was investigated by using Steady State Fluorescence (SSF) method. Scattered light, I sc and fluorescence intensity, I fl were monitored against temperature during heating and cooling processes to investigate phase transitions. Two regions were observed during the heating and cooling processes. At the high temperature region, double helix to coil (h-c) transition took place. However, during the cooling process coil to double helix (c-h) transitions occurred at low temperature region. Transition energies were determined using the Arrhenius treatment, and found to be strongly correlated with the agarose content in the gel system. Transition temperatures were determined from the derivative of the sigmoidal transition paths and found to be increased by increasing agarose content in both cases

EFFECT OF INTRAVESICAL HYALURONIC ACID TREATMENT ON BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS

Purpose: Our study aims to evaluate the efficacy of hyaluronic acid (HA) on interstitial cystitis patients admitted to our clinic with the diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC)