Vesicle-vesicle fusion promoted by the Atg8-family autophagy protein LC3C: relevance of the N-terminal region.

Among the MAP1LC3/LC3 subfamily of Atg8 proteins, LC3B and LC3C constitute the most and least studied members, respectively, LC3B being generally considered as an autophagosomal marker and a canonical representative of the LC3 subfamily. In several recent studies, LC3C has emerged as an important modulator in various processes of cell homeostasis. Our own research data demonstrate that LC3C induces higher levels of tethering and of intervesicular lipid mixing than LC3B. LC3C contains a peculiar N-terminal region, different from the other Atg8-family protein members. Using a series of mutants, we have shown that the N-terminal region of LC3C is responsible for the enhanced vesicle tethering, membrane perturbation and vesicle-vesicle fusion activities of LC3C as compared to LC3B.Abbreviations: ATG: autophagy related; GABARAP: gamma-aminobutyric acid receptor associated protein; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PC: phosphatidyl choline; PE: phosphatidylethanolamine; PEmal: maleimide-derivatized PE; PtdIns: phosphatidylinositol.

Biological and chemical characterization in relation to the yield of radish (Raphanus sativus L.) nourished with humus from plant residues.

The increase in prices of fertilizers, energy and other materials necessary for the industry triggered a global economic crisis. Reason that was investigated on the biological and chemical characteristics in relation to the yield of radish nourished with humus from plant residue. The objective was to determine the appropriate dose of humus to obtain greater yield and its relationship with the chemical and biological characteristics of the radish. It is based on applied methodology with an experimental approach; Therefore, the Completely Random Block Design model was used, which consisted of 3 blocks and 5 treatments that were T1 with 0, T2 with 4, T3 with 6, T4 with 8 and T5 with 10 t/ha of humus and They applied 15 days after sowing. The physical characteristics of the radish were evaluated and processed using analysis of variance and Duncan. Concentration of elements in leaves and stomatal density were also analyzed. It was determined that T5 stood out in total plant length with 28.95 cm, plant weight with 76.87 g, equatorial diameter with 4,404 cm and commercial yield with 20,296 t/ha. Nitrogen consumption in relation to yield with 247.44 kg/ha. Stomatal density 459 stomata/mm2 and profitability with 150% and nutrient concentration in leaves highlighted T4 with N, K, Ca, Mg, Mo and Zn. It concludes that T5 stood out with 20,296 t/ha, which differed by 26.04% in relation to the control (T1) with 15,011 t/ha. Therefore, this dose added nutrients to the soil that improved the availability for plant absorption and this influenced the concentration of nutrients in leaves such as N, P and Fe and stomatal density with 459 stomata/mm2, which had a response in good development, strengthening against environmental stress and therefore greater performance.

The N-terminal region of the ATG8 autophagy protein LC3C is essential for its membrane fusion properties.

Autophagy is a catabolic process in which a double-membrane organelle, the autophagosome (AP), engulfs cellular components that will be degraded in the lysosomes. ATG8 protein family members participate at various stages of AP formation. The present study compares the capacity to induce lipid-vesicle tethering and fusion of two ATG8 family members, LC3B and LC3C, with model membranes. LC3B is the most thoroughly studied ATG8 protein. It is generally considered as an autophagosomal marker and a canonical representative of the LC3 subfamily. LC3C is less studied, but recent data have reported its implication in various processes, crucial to cellular homeostasis. The results in this paper show that LC3C induces higher levels of tethering and of intervesicular lipid mixing than LC3B. As the N-terminus of LC3C is different from that of the other family members, various mutants of the N-terminal region of both LC3B and LC3C were designed, and their activities compared. It was concluded that the N-terminal region of LC3C was responsible for the enhanced vesicle tethering, membrane perturbation and vesicle-vesicle fusion activities of LC3C as compared to LC3B. The results suggest a specialized function of LC3C in the AP expansion process.

Ceramide regulation of autophagy: A biophysical approach.

Specific membrane lipids play unique roles in (macro)autophagy. Those include phosphatidylethanolamine, to which LC3/GABARAP autophagy proteins become covalently bound in the process, or cardiolipin, an important effector in mitochondrial autophagy (or mitophagy). Ceramide (Cer), or N-acyl sphingosine, is one of the simplest sphingolipids, known as a stress signal in the apoptotic pathway. Moreover, Cer is increasingly being recognized as an autophagy activator, although its mechanism of action is unclear. In the present review, the proposed Cer roles in autophagy are summarized, together with some biophysical properties of Cer in membranes. Possible pathways for Cer activation of autophagy are discussed, including specific protein binding of the lipid, and Cer-dependent perturbation of bilayer properties. Cer generation of lateral inhomogeneities (domain formation) is given special attention. Recent biophysical results, including fluorescence and atomic force microscopy data, show Cer-promoted enhanced binding of LC3/GABARAP to lipid bilayers. These observations could be interpreted in terms of the putative formation of Cer-rich nanodomains.

Analysis of the biological and chemical characteristics of cabbage (Brassica oleracea var. Capitata L.) Fed with compost based on sugarcane residues.

The pandemic and the geopolitical conflict between Russia and Ukraine are events that have caused economic instability in Peru. Reason that was investigated on the analysis of the biological and chemical characteristics of cabbage fed with compost based on sugarcane residues. The objective was to analyze the physical, chemical and biological characteristics of cabbage from the adequate dose of compost based on sugarcane residues and distance between plants. It is based on the methodology applied with an experimental approach, for which the Completely Random Block Design with a 4x 2 factorial arrangement was used, which consisted of 3 blocks and 8 treatments that were the combination: F1 with 0, F2 with 8, T3 with 10 and F4 with 12 t/ha and spacing (D1) with 0.30 m between plants and 0.60 m between rows and (D2) with 0.35 m between plants and 0.60 m between rows. The physical characteristics of cabbage were evaluated and processed by analysis of variance, nutrient concentrations in leaves and stomatal density were analyzed. The results determined that T7 stood out in plant height with 41.88 cm, yield with 26.76 tn/ha and T6 in root length with 20.22 cm. In chemical analysis of leaves T1 stood out in nitrogen, phosphorus, potassium and T4 in calcium, magnesium and sulfur. In T7 stomata density with 977 stomata/mm2. It concludes that at an adequate dose and greater distance that T7 stands out in the concentration of nutrients that are within normal values and high density of stomata; Therefore, these characteristics influenced the optimal biochemical reactions, which obtained good development and yield that differed at 51.39% and 32.17% with respect to the controls T1 and T5.

Definition of unconformities based on radiometric tool.

The concentrations of U-238, Th-232, and K-40 measured with a portable gamma-ray spectrometer in cutting samples of two exploratory wells allowed the radiometric characterization of Cretaceous Rancheria sub-basin rocks and the definition of twelve (12) zones according to paleo-redox facies. The Th/Ua (authigenic uranium) and Th/U ratio greater than 7 (seven) indicates paleo-redox conditions related to oxygenation changes and detrital material input during deposition and terrestrial freshwater environment. However, the Lagunitas, Aguas Blancas, La Luna, and Molino formations characterize by facies from sub-oxic (dioxic) to anoxic redox. In the Aguas Blancas and Molino Formations, pyrite and the high uranium measurements determine an anoxic and euxinic environment. The high values of both + uranium and authigenic uranium in the La Luna and Molino formations relate to the conservation of organic matter, which is an essential factor in the generation of hydrocarbons. The abrupt changes of both K/U and Th/U identify potential sequential or genetic limit surfaces (e.g., maximum flooding surfaces), limiting such zones. Based on radiometric behavior, this research permitted identifying eight Cretaceous to Miocene unconformities in the area, three of them reported here for the first time.

Effect of ATG12-ATG5-ATG16L1 autophagy E3-like complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion.

In macroautophagy, the autophagosome (AP) engulfs portions of cytoplasm to allow their lysosomal degradation. AP formation in humans requires the concerted action of the ATG12 and LC3/GABARAP conjugation systems. The ATG12-ATG5-ATG16L1 or E3-like complex (E3 for short) acts as a ubiquitin-like E3 enzyme, promoting LC3/GABARAP proteins anchoring to the AP membrane. Their role in the AP expansion process is still unclear, in part because there are no studies comparing six LC3/GABARAP family member roles under the same conditions, and also because the full human E3 was only recently available. In the present study, the lipidation of six members of the LC3/GABARAP family has been reconstituted in the presence and absence of E3, and the mechanisms by which E3 and LC3/GABARAP proteins participate in vesicle tethering and fusion have been investigated. In the absence of E3, GABARAP and GABARAPL1 showed the highest activities. Differences found within LC3/GABARAP proteins suggest the existence of a lipidation threshold, lower for the GABARAP subfamily, as a requisite for tethering and inter-vesicular lipid mixing. E3 increases and speeds up lipidation and LC3/GABARAP-promoted tethering. However, E3 hampers LC3/GABARAP capacity to induce inter-vesicular lipid mixing or subsequent fusion, presumably through the formation of a rigid scaffold on the vesicle surface. Our results suggest a model of AP expansion in which the growing regions would be areas where the LC3/GABARAP proteins involved should be susceptible to lipidation in the absence of E3, or else a regulatory mechanism would allow vesicle incorporation and phagophore growth when E3 is present.

Ceramide enhances binding of LC3/GABARAP autophagy proteins to cardiolipin-containing membranes.

Macroautophagy, or autophagy, is a process in which cell macromolecules, or even organelles, are engulfed in a double-membrane vesicle, the autophagosome, and directed to a lysosome. Among autophagy-related proteins, LC3/GABARAP constitute a protein family derived from yeast Atg8. They play important roles in autophagosome formation, binding future cargo organelles and promoting autophagosome growth. The involvement of specific lipids in this process is poorly understood. The present study explores the interaction of LC3/GABARAP proteins with phospholipid monolayers and bilayers based on phosphatidylcholine or on sphingomyelin. Cardiolipin is found to be essential for the protein interaction with such bilayers, as measured through gradient centrifugation experiments, while ceramide markedly increases binding. Giant unilamellar vesicles examined under confocal fluorescence microscopy reveal that ceramide segregates laterally into very rigid domains, while GABARAP binds only the more fluid regions, suggesting that the enhancing role of ceramide is exerted by the minority of ceramide molecules dispersed in the fluid phase. Although in further autophagy steps the LC3/GABARAP proteins are covalently bound to a phospholipid, this is not the case in our system, thus it is proposed that the observed ceramide effects would correspond to very early stages in the process, such as cargo recognition.

Role of defects in the mechanical properties of graphene-copper heterostructures.

Through molecular dynamics simulations of tensile tests, the role that vacancies and Stone-Wales defects play in the mechanical properties of sandwich-like heterostructures, composed by graphene and two symmetric copper layers at nanoscale, is studied. The dependence on the armchair and zigzag chiralities of the graphene layer is also investigated. During elastic deformation, defects negatively affect the mechanical response. However, defective systems can show an improvement of the plastic properties. Vacancies have a stronger impact compared to Stone-Wales defects. Elasticity, toughness, and ductility are enhanced along the zigzag chirality, while stiffness is improved along the armchair direction. The Poisson's ratio was calculated for all graphene-copper heterostructures. At a critical strain it becomes negative along the thickness direction, preserving the auxetic property at higher strains. In general, the behavior is governed by the graphene response. Our findings can be useful to understand the strengthening mechanism induced by this two-dimensional material in metals like copper and for the design of similar systems.

Autophagy protein LC3C binding to phospholipid and interaction with lipid membranes.

Autophagy is a process in which parts of the eukaryotic cell are selectively degraded in the lysosome. The materials to be catabolized are first surrounded by a double-membrane structure, the autophagosome. Autophagosome generation is a complex event, in which many proteins are involved. Among the latter, yeast Atg8 or its mammalian orthologues are essential in autophagosome membrane elongation, shaping and closure. A subfamily of the human Atg8 orthologues is formed by the proteins LC3A, LC3B, and LC3C. Previous studies suggest that, at variance with the other two, LC3C does not participate in cardiolipin-mediated mitophagy. The present study was devoted to exploring the binding of LC3C to lipid vesicles, bilayers and monolayers, and the ensuing protein-dependent perturbing effects, in the absence of the mitochondrial lipid cardiolipin. All Atg8 orthologues are covalently bound to a phospholipid prior to their involvement in autophagosome elongation. In our case, a mutant in the C-terminal amino acid, LC3C G126C, together with the use of a maleimide-derivatized phosphatidyl ethanolamine, ensured LC3C lipidation, up to 100% under certain conditions. Ultracentrifugation, surface pressure measurements, spectroscopic and cryo-electron microscopic techniques revealed that lipidated LC3C induced vesicle aggregation (5-fold faster in sonicated than in large unilamellar vesicles) and inter-vesicular lipid mixing (up to 82%), including inner-monolayer lipid mixing (up to 32%), consistent with in vitro partial vesicle fusion. LC3C was also able to cause the release of 80-90% vesicular aqueous contents. The data support the idea that LC3C would be able to help in autophagosome elongation/fusion in autophagy phenomena.

LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs.

Externalization of the phospholipid cardiolipin (CL) to the outer mitochondrial membrane has been proposed to act as a mitophagy trigger. CL would act as a signal for binding the LC3 macroautophagy/autophagy proteins. As yet, the behavior of the LC3-subfamily members has not been directly compared in a detailed way. In the present contribution, an analysis of LC3A, LC3B and LC3C interaction with CL-containing model membranes, and of their ability to translocate to mitochondria, is described. Binding of LC3A to CL was stronger than that of LC3B; both proteins showed a similar ability to colocalize with mitochondria upon induction of CL externalization in SH-SY5Y cells. Besides, the double silencing of LC3A and LC3B proteins was seen to decrease CCCP-induced mitophagy. Residues 14 and 18 located in the N-terminal region of LC3A were shown to be important for its recognition of damaged mitochondria during rotenone- or CCCP-induced mitophagy. Moreover, the in vitro results suggested a possible role of LC3A, but not of LC3B, in oxidized-CL recognition as a counterweight to excessive apoptosis activation. In the case of LC3C, even if this protein showed a stronger CL binding than LC3B or LC3A, the interaction was less specific, and colocalization of LC3C with mitochondria was not rotenone dependent. These results suggest that, at variance with LC3A, LC3C does not participate in cargo recognition during CL-mediated-mitophagy. The data support the notion that the various LC3-subfamily members might play different roles during autophagy initiation, identifying LC3A as a novel stakeholder in CL-mediated mitophagy. Abbreviations: ACTB/ß-actin: actin beta; Atg8: autophagy-related 8; CL: cardiolipin; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DMSO: dimethyl sulfoxide; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DTT: DL-dithiothreitol; FKBP8: FKBP prolyl isomerase 8; GABARAP: GABA type A receptor associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GFP: green fluorescent protein; IMM: inner mitochondrial membrane; LUV/LUVs: large unilamellar vesicle/s; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; NME4/NDPK-D/Nm23-H4: NME/NM23 nucleoside diphosphate kinase 4; O/A: oligomycin A + antimycin A; OMM: outer mitochondrial membrane; PA: phosphatidic acid; PC: phosphatidylcholine; PG: phosphatidylglycerol; PINK1: PTEN induced putative kinase 1; PtdIns4P: phosphatidylinositol-4-phosphate; Rho-PE: lissamine rhodamine phosphatidylethanolamine; SUV/SUVs: small unilamellar vesicle/s.

Perception and Knowledge of Mercury by Occupationally Exposed Health Care Personnel.

Thermometers and baumanometers frequently contain mercury, a toxic heavy metal. Inadequate management of this substance can constitute an occupational hazard by exposing health care professionals to health risks including memory loss, psychosomatic symptoms, fatigue, and other signs of cognitive dysfunction as reported in several studies. PURPOSE: To assess Mexico's health care professionals' health and mercury-related knowledge and risk perception and to explore the measurement properties of a questionnaire assessing that level of knowledge. MATERIALS AND METHODS: Mixed methodology. A quantitative, cross-sectional study was conducted to measure health care professionals' knowledge of mercury and to validate an instrument using a Rasch analysis in 160 professionals. A qualitative study involving in-depth interviews was conducted to identify participants' risk perception for mercury exposure. RESULTS: The total knowledge of mercury was 19.0 ± 2.0 on a scale of 0 to 28 points. The scores for medical specialists were significantly (P < .001) higher, ranging between 20.0 ± 2.05 and 23.0 ± 1.63. In general, the level of risk perception for mercury exposure was low. The questionnaire presented a reasonable fit to the Rasch model (good item fit with a Bonferroni-adjusted P = .000714). The response categories of three items were collapsed, and two pairs of items were bundled into two super items. CONCLUSION: The levels of the knowledge of the health and safety risks and risk perception for mercury exposure in the Mexican health care professionals evaluated were low. Health care professionals should receive comprehensive training in the safe use and health risks of mercury.

Molecular and mesoscopic geometries in autophagosome generation. A review.

Autophagy is an essential process in cell self-repair and survival. The centre of the autophagic event is the generation of the so-called autophagosome (AP), a vesicle surrounded by a double membrane (two bilayers). The AP delivers its cargo to a lysosome, for degradation and re-use of the hydrolysis products as new building blocks. AP formation is a very complex event, requiring dozens of specific proteins, and involving numerous instances of membrane biogenesis and architecture, including membrane fusion and fission. Many stages of AP generation can be rationalised in terms of curvature, both the molecular geometry of lipids interpreted in terms of 'intrinsic curvature', and the overall mesoscopic curvature of the whole membrane, as observed with microscopy techniques. The present contribution intends to bring together the worlds of biophysics and cell biology of autophagy, in the hope that the resulting cross-pollination will generate abundant fruit.

Evaluation of naturally occurring radioactive materials (NORM) in the soil, in a potential area for unconventional reservoirs in the Rancheria Sub-Basin.

Naturally occurring radioactive elements depend on lithology geogenic characteristics, such as depositional, environmental, or diagenetic. Thus, evaluating these elements constitutes a tool to define ionizing radiation effect from rocky sequences. This study carried out in the Rancheria Sub-Basin establishes both characterization and assessment of this kind of material, known as NORM. The sampling included uranium-238, thorium-232, potassium-40, radon-226, and radon-222 in soil samples, cutting samples from the Molino-1 well, and radon in surface water. Bases on a radiometric methodology with a gamma-ray spectrometer for uranium-238, thorium-232, and potassium-40 and emanometric with ionizing chambers for radio-226 and radon-222. The analysis and results of the activity concentrations in soil samples of U-238, Th-232, K-40, and Ra-226 are 11.7 BqKg-1, 33.0 BqKg-1, 424.5 BqKg-1, and 15.59 BqKg-1, respectively, among the acceptable global averages. However, in some areas, observed values indicate high activity concentrations of U-238, Th-232, K-40, Ra-226, and Rn-222 in the soil of 50.2 BqKg-1, 62.8 BqKg-1, 1596.3 BqKg-1, 44.25 BqKg-1, and 112546.79 Bqm-3, respectively. Those activity concentrations were associated with zone lithology.

Zirconium retention for minimizing environmental risk: Role of counterion and clay mineral.

Zr(IV) together with U(IV) are the major components of high-level radionuclide waste (HLRW) and spent nuclear fuel (SNF) from nuclear power plants. Thus, their retention in the waste disposal is of great importance for the environmental risk control. Here, the influence of clay minerals on the retention of Zr(IV), as component of the nuclear waste and as chemical analogues of U(IV), has been evaluated. Three clay minerals, two bentonites and one saponite, were hydrothermally treated with three zirconium salts. A structural study at long-range order by X-ray diffraction and short-range order by NMR was performed to evaluate the generation of new zirconium phases and degradation of the clay minerals. Three immobilization mechanisms were observed: i) cation exchange of ZrO2+ or Zr4+ by clay minerals, ii) the precipitation/crystallization of ZrO2, and, iii) the chemical interaction of zirconium with the clay minerals, with the formation of zirconium silicates.

Management of odonto-stomatological emergencies during the COVID-19 alarm state in dental clinics in the Autonomous Community of Madrid (CAM), Spain: An observational study.

BACKGROUND: Odontology practice has been severely compromised by the pandemic caused by COVID-19 and Spain is one of the countries with higher incidence. Our aim with this study is to find out the number of cases and type of odonto-stomatological emergencies (OSE) treated in four dental clinics of the Madrid capital area and region (CAM) in the period covered between March 17th and 4th of May. MATERIAL AND METHODS: We search the cases in the demographic/epidemiological databases of the CAM regional government and the Illustrious Official College of Dentists and Stomatologists of the First Region (Madrid). RESULTS: We found that the most prevalent pathology was acute apical periodontitis whereas odontogenic abscess showed the lowest frequency. Prosthetic-orthodontic OSE represented 14% of cases. CONCLUSIONS: In this period of time, the most prevalent pathology acute apical periodontitis, odontogenic abscess reported the lowest frequency and prosthetic-orthodontic treatments were the third in number of cases. Most of OSE were resolved, without referring the patient to a hospital emergency department.

Effects of biaxial strain on the impurity-induced magnetism in P-doped graphene and N-doped silicene: a first principles study.

The effects of biaxial strain on the impurity-induced magnetism in P-doped graphene (P-graphene) and N-doped silicene (N-silicene) are studied by means of spin-polarized density functional calculations, using the supercell approach. The calculations were performed for three different supercell sizes 4 × 4, 5 × 5, and 6 × 6, in order to simulate three different dopant concentrations 3.1, 2.0 and 1.4%, respectively. For both systems, the calculated magnetic moment is 1.0 µ B per impurity atom for the three studied concentrations. From the analysis of the electronic structure and the total energy as a function of the magnetization, we show that a Stoner-type model describing the electronic instability of the narrow impurity band accounts for the origin of sp-magnetism in P-graphene and N-silicene. Under biaxial strain the impurity band dispersion increases and the magnetic moment gradually decreases, with the consequent collapse of the magnetization at moderate strain values. Thus, we found that biaxial strain induces a magnetic quantum phase transition in P-graphene and N-silicene.

Extensión de la indicación de terapia fotodinámica dirigida vascular con padeliporfina (WST11): resultados de un estudio multicéntrico latinoamericano del cáncer de próstata / Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study

Objetivos: Explorar la proporción de pacientes con cáncer de próstata localizado (CaP) de mayor riesgo que se convertiría en una biopsia negativa con seguridad 12 meses después de la terapia focal no térmica con terapia fotodinámica dirigida vascular de padeliporfina (TFV). Métodos: Estudio multicéntrico en un escenario de antígeno prostático específico (PSA) ≤ 20 ng/ml y patrón 3 de Gleason de volúmenes objetivo de CaP variable o patrón 4 de Gleason secundario de volumen bajo. Todos los pacientes recibieron TFV, que consistió en 4 mg/kg de padeliporfina intravenosa activada por fibras difusoras de luz en la próstata. La próstata se biopsió al inicio del estudio y a los meses 6 y 12. El PSA, los resultados funcionales informados por los pacientes y los cuestionarios de calidad de vida (CdV) se registraron al inicio y a los meses 3, 6 y 12; los eventos adversos (EA) se registraron a lo largo del estudio. Resultados: En la población con intención de tratar (n = 81), la proporción de pacientes con biopsias negativas al mes 12 fue del 74% (60/81 pacientes, IC 95%: 63,1, 83,2%). En la población por protocolo, la proporción fue del 79% (58/73 pacientes, IC 95%: 68,4, 88,0%). Los resultados del cuestionario indicaron una ligera mejoría en la función urinaria y un deterioro limitado en la función sexual. No se observó diferencia en la CdV con el tiempo. Un total de 42/81 (52%) pacientes comunicaron EA leves o moderados y 4 de 81 (4,9%) experimentaron EA graves, todos resueltos sin secuelas. No se informó fototoxicidad, evento cardiovascular, fístula o incontinencia urinaria prolongada, cáncer secundario o muerte. Conclusiones: Los resultados respaldan la eficacia, la seguridad y la CdV asociadas con el tratamiento focal de padeliporfina para el CaP localizado de riesgo bajo/intermedio

Objectives: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). Methods: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. Results: In the intention-to-treat population (n = 81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%, 83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%, 88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. Conclusions: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study. / Extensión de la indicación de terapia fotodinámica dirigida vascular con padeliporfina (WST11): resultados de un estudio multicéntrico latinoamericano del cáncer de próstata.

OBJECTIVES: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). METHODS: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. RESULTS: In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. CONCLUSIONS: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa.