Biomarker-Oriented Therapy in Bladder and Renal Cancer

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor—tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.     

Thermal behavior and morphology of polyamide 6 based multicomponent blends

The thermal behavior and morphology of multicomponent blends based on PA6, polyamide 6 (PA6)/styrene–acrylonitirle copolymer (SAN), PA6/acrylonitrile–butadiene–styrene terpolymer (ABS), and their compatibilized blends with styrene–acrylonitrile–maleic anhydride copolymer (SANMA) were studied using DSC and SEM. The blends were prepared in a twin‐screw extruder under similar processing conditions, keeping the PA6 content fixed at 50 wt %. It was found that, in all the blends, the second component had a nucleating effect and improved the overall degree and rate of crystallization of PA6, whereas addition of a compatibilizer slightly diminished these effects and resulted in significant changes in the blend morphology. The nucleating effect and consequent changes in the crystallization behavior was attributed to the presence of SAN, which is a common component in all the blends. The T_g of PA6 in the blends with a cocontinuous morphology, due to the connectivity between the phases, is higher than in the blends with a disperse‐type morphology. The compatibilized blends have a lower crystallization rate and nucleation ability with a cocontinuous morphology, whereas the uncompatibilized blends have a higher crystallization rate with a higher nucleation ability and a disperse and/or a coarse cocontinuous morphology. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2753–2759, 2002     

Microtubule nucleation by gamma-tubulin-containing rings in the centrosome

The microtubule cytoskeleton of animal cells does not assemble spontaneously, but instead requires the centrosome. This organelle consists of a pair of centrioles surrounded by a complex collection of proteins known as the pericentriolar material (PCM). The PCM is required for microtubule nucleation. The minus, or slow-growing, ends of microtubules are embedded in the PCM and the plus, or fast-growing, ends project outwards into the cytoplasm during interphase, or into the spindle apparatus during mitosis. gamma-Tubulin is the only component of the PCM that is so far implicated in microtubule nucleation. Here we use immuno-electron microscopic tomography to show that gamma-tubulin is localized in ring structures in the PCM of purified centrosomes without microtubules. When these centrosomes are used to nucleate microtubule growth, gamma-tubulin is localized at the minus ends of the microtubules. We conclude that microtubule-nucleating sites within the PCM are ring-shaped templates that contain multiple copies of gamma-tubulin.     

X-ray fluorescence investigation of the Ga distribution in Cu(In,Ga)Se2 thin films

The efficiencies of Cu(In,Ga)Se₂/CdS/ZnO solar cell devices in which the absorbers are produced by classical two-step processes are significantly lower that those in which co-evaporated absorbers are used. A significant problem related to two-step growth processes is the reported segregation of Ga towards the Mo back contact, resulting in separate CuInSe₂ and CuGaSe₂ phases. Furthermore, it is often reported that material losses (especially In and Ga) occur during high-temperature selenization of metallic precursors. In this study, X-ray fluorescence (XRF) analysis was used to study the diffusion behaviour of the chalcopyrite elements in single-stage and two-stage processed Cu(In,Ga)Se₂ thin films. This relatively simple characterization technique proved to be very reliable in determining the degree of selenium incorporation, possible material losses and the in-depth compositional uniformity of samples at different stages of processing. This information is especially important in the case of two-stage growth processes, involving high-temperature selenization steps of metallic precursors. Device quality Cu(In,Ga)Se₂ thin films were prepared by a relatively simple and reproducible two-step growth process in which all the metals were evaporated from one single crucible in a selenium-containing environment. The precursors were finally treated in an H₂Se/Ar atmosphere to produce fully reacted films. XRF measurement indicated no loss of In or Ga during this final selenization step, but a significant degree of element diffusion which depended on the reaction temperature. It was also possible to produce Cu(In,Ga)Se₂ thin films with an appreciable amount of Ga in the near-surface region without separated CuInSe₂ and CuGaSe₂ phases.     

Influence of GaSe deposition temperature on the structural properties and in-depth compositional features of two-step grown Cu(In,Ga)Se2 thin films

In this study, Cu(In,Ga)Se₂ thin films were prepared by a classical two-stage growth process, which involved the selenization of thermally evaporated InSe/Cu/GaSe precursors. During the precursor-formation step the InSe and Cu were always deposited at 200 °C, while the GaSe layers were deposited at temperatures between 200 °C and 400 °C. The respective precursors were simultaneously selenized under identical conditions in elemental Se vapor. In cases where the GaSe layers were deposited at low temperatures around 200 °C, X-ray fluorescence (XRF) analysis revealed a large variation in element concentration with sample depth after selenization. In correspondence, X-ray diffraction (XRD) studies revealed the presence of separate CuInSe₂ and CuGaSe₂ phases in these specific samples. Optimum structural properties were obtained when the GaSe films were deposited at 300 °C, followed by selenization. In general, these films were uniform and dense and XRD studies revealed single-phase Cu(In,Ga)Se₂ material. Even more importantly, XRF analysis revealed a remarkable improvement in in-depth compositional uniformity when the GaSe films were deposited at or above 300 °C. An increase in GaSe deposition temperature to 400 °C, however, resulted in a deterioration in the structural features of the Cu(In,Ga)Se₂ thin films. In contradiction with other reports, these results indicated that the in-depth composition uniformity and especially the Ga diffusion profile in two-step grown Cu(In,Ga)Se₂ thin films can be controlled. The crucial factor influencing the depth profile of these films is the GaSe deposition temperature during the precursor formation step.     

Isolation and characterization of a unique glycoprotein from lavage of chicken lungs and lamellar organelles

A major glycoprotein with an estimated molecular weight by sodium dodecylsulfate-acrylamide gel electrophoresis of 36,000 daltons has been found in lavage material of normal chicken lung. Amino acid and carbohydrate analyses of this glycoprotein indicated the presence of hydroxyproline, a high percentage of glycine, sialic acid, mannose, galactose, fucose, and glucosamine. Threonine is the NH2-terminal residue of the glycoprotein. A similar glycoprotein of the same molecular weight, NH2-terminus, amino acid, and carbohydrate composition has been found in lamellar organelles isolated from normal chicken lung. The data indicate that this unique collagen-like glycoprotein, which is similar to a major alveolar glycoprotein found in mammals, including patients with alveolar proteinosis, is also a major protein of avian airways. Because avian airways contain no Clara, ciliated, or goblet cells but do contain type II cells as the only secretory airway cells with lamellar organelles, it is likely that in birds this glycoprotein may be a product of type II cells.     

Why it is advisable to keep wR = 1 and Q = 1 for photons and electrons

It has been well known for a long time that the biological effectiveness of photons and electrons depends on the mean linear energy transfer (LET) of the radiation considered, e.g. (60)Co gamma rays are less effective than soft or hard X rays. Nevertheless, the protection and operational dose quantities applied in radiological protection include weighting factors, w(R) or Q, respectively, which were set to 1 for all low-LET radiations. Lack of precise information, simplicity and general practical considerations are the main arguments for this convention. However, a more detailed discussion on the practical aspects supporting this procedure is missing. The paper discusses in more detail some of these aspects regarding internal and external exposure situations, which may support the idea of continuing to use w(R) = 1 for photons and electrons and, correspondingly, using Q(L) = 1 for L < 10 keV microm(-1).     

Biological degradation of aflatoxin B1 by Rhodococcus erythropolis cultures

Aflatoxin contamination of food and grain poses a serious economic and health problem worldwide, but particularly in Africa. Aflatoxin B(1) (AFB(1)) is extremely mutagenic, toxic and a potent carcinogen to both humans and livestock and chronic exposure to low levels of AFB(1) is a concern. In this study, the biodegradation of aflatoxin B(1) (AFB(1)) by Rhodococcus erythropolis was examined in liquid cultures using thin layer chromatography (TLC), high performance liquid chromatography (HPLC), electro spray mass spectrometry (ESMS) and liquid chromatography mass spectrometry (LCMS). AFB(1) was effectively degraded by extracellular extracts from R. erythropolis liquid cultures. Results indicated that the degradation is enzymatic and that the enzymes responsible for the degradation of AFB(1) are extracellular and constitutively produced. Furthermore, the biodegradation of AFB(1) when treated with R. erythropolis extracellular fraction coincided with a loss of mutagenicity, as evaluated by the Ames test for mutagenicity.     

Reversible monocular blindness complicating Churg-Strauss syndrome

A 76-year-old woman hospitalized for treatment of an inferior vena cava thrombus was noted to have eosinophilia as well as asthma, peripheral neuropathy, jaw claudication and visual loss. Pathological review of a temporal artery biopsy revealed vasculitis with eosinophils but no giant cells. Treatment with high dose corticosteroids resulted in improvement of visual acuity from hand motion to 20/60. Whereas at least 6 cases of temporal artery involvement with Churg-Strauss syndrome have been reported, visual loss has occurred in only 3 patients. In each of these cases, visual loss was permanent.