Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Biomolecules, MDPI AG, Vol. 12, No. 11 ( 2022-10-26), p. 1570-
    Abstract: In the past decade, defective DNA repair has been increasingly linked with cancer progression. Human tumors with markers of defective DNA repair and increased replication stress exhibit genomic instability and poor survival rates across tumor types. Seminal studies have demonstrated that genomic instability develops following inactivation of BRCA1, BRCA2, or BRCA-related genes. However, it is recognized that many tumors exhibit genomic instability but lack BRCA inactivation. We sought to identify a pan-cancer mechanism that underpins genomic instability and cancer progression in BRCA-wildtype tumors. Methods: Using multi-omics data from two independent consortia, we analyzed data from dozens of tumor types to identify patient cohorts characterized by poor outcomes, genomic instability, and wildtype BRCA genes. We developed several novel metrics to identify the genetic underpinnings of genomic instability in tumors with wildtype BRCA. Associated clinical data was mined to analyze patient responses to standard of care therapies and potential differences in metastatic dissemination. Results: Systematic analysis of the DNA repair landscape revealed that defective single-strand break repair, translesion synthesis, and non-homologous end-joining effectors drive genomic instability in tumors with wildtype BRCA and BRCA-related genes. Importantly, we find that loss of these effectors promotes replication stress, therapy resistance, and increased primary carcinoma to brain metastasis. Conclusions: Our results have defined a new pan-cancer class of tumors characterized by replicative instability (RIN). RIN is defined by the accumulation of intra-chromosomal, gene-level gain and loss events at replication stress sensitive (RSS) genome sites. We find that RIN accelerates cancer progression by driving copy number alterations and transcriptional program rewiring that promote tumor evolution. Clinically, we find that RIN drives therapy resistance and distant metastases across multiple tumor types.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2701262-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Cancers, MDPI AG, Vol. 14, No. 9 ( 2022-04-19), p. 2056-
    Abstract: Hepatocellular Carcinoma (HCC) is the most common liver malignancy and third leading cause of cancer death worldwide. For early- and intermediate-stage disease, liver-directed therapies for locoregional control, or down-staging prior to definitive surgical therapy with hepatic resection or liver transplantation, have been studied broadly, and are the mainstays of current treatment guidelines. As HCC incidence has continued to grow, and with more patients presenting with advanced disease, our current treatment modalities do not suffice, and better therapies are needed to improve disease-specific and overall survival. Until recently, sorafenib was the only systemic therapy utilized, and was associated with dismal results. The advent of immuno-oncology has been of significant interest, and has changed the paradigm of therapy for HCC. Lately, combination regimens including atezolizumab plus bevacizumab; durvalumab plus tremelimumab; and pembrolizumab plus Lenvatinib have shown impressive responses of between 25–35%; this is much higher than responses observed with single agents. Complete responses with checkpoint inhibitor therapy have been observed in advanced-stage HCC patients. These dramatic results have naturally led to several questions. Can or should checkpoint inhibitors, or other immunotherapy combinations, be used routinely before resection or transplant? Is there a synergistic effect of immunotherapy with locoregional therapy, and will pre-treatment increase disease-free survival after surgical intervention? Is it immunologically safe to use these therapies prior to transplantation? Much is still to be learned in terms of the dosing, timing, and overall utility of the use of immune checkpoint inhibitors for pre-transplant care and down-staging. More studies will be needed to understand the management of adverse events while maximizing the therapeutic window of these agents. In this review, we look at the current data on therapy with immune checkpoint inhibitors in advanced HCC, with a focus on pre-transplant treatment prior to liver transplant.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Viruses, MDPI AG, Vol. 12, No. 9 ( 2020-09-08), p. 1003-
    Abstract: Maternal influenza A viral infections in humans are associated with low birth weight, increased risk of pre-term birth, stillbirth and congenital defects. To examine the effect of maternal influenza virus infection on placental and fetal growth, pregnant C57BL/6 mice were inoculated intranasally with influenza A virus A/CA/07/2009 pandemic H1N1 or phosphate-buffered saline (PBS) at E3.5, E7.5 or E12.5, and the placentae and fetuses collected and weighed at E18.5. Fetal thymuses were pooled from each litter. Placentae were examined histologically, stained by immunohistochemistry (IHC) for CD34 (hematopoietic progenitor cell antigen) and vascular channels quantified. RNA from E7.5 and E12.5 placentae and E7.5 fetal thymuses was subjected to RNA sequencing and pathway analysis. Placental weights were decreased in litters inoculated with influenza at E3.5 and E7.5. Placentae from E7.5 and E12.5 inoculated litters exhibited decreased labyrinth development and the transmembrane protein 150A gene was upregulated in E7.5 placentae. Fetal weights were decreased in litters inoculated at E7.5 and E12.5 compared to controls. RNA sequencing of E7.5 thymuses indicated that 957 genes were downregulated ≥2-fold including Mal, which is associated with Toll-like receptor signaling and T cell differentiation. There were 28 upregulated genes. It is concluded that maternal influenza A virus infection impairs fetal thymic gene expression as well as restricting placental and fetal growth.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2516098-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 9 ( 2023-09-14), p. 1374-
    Abstract: The objective of this manuscript was to review the indications, efficacy, and safety of a 585 nm pulsed dye laser (PDL) in non-malignant laryngeal lesions. Following the PRISMA statement recommendations, three independent authors searched for articles published in PubMed/MEDLINE, the Cochrane Library, Google Scholar, Scielo, and Web of Science. A bias analysis was performed following NICE guidance tools. From the 506 identified publications, 19 observational studies met the inclusion criteria. The PDL improves vocal quality objectively and subjectively in vascular lesions (p 〈 0.005) and improves vocal quality in patients with dysplasia/leukoplasia without changing the natural history of the disease compared to other treatments. Reinke’s edema and granulomas require an average of 1.5 PDL sessions for resolution. Treatment of recurrent respiratory papillomatosis requires multiple sessions, with complete remission achieved in 50–70% of patients. Regardless of the lesion, the tolerance of the procedure under local anesthesia is exceptional (84–97%), and the results in terms of regression and vocal quality are promising. The complication rate is minimal, and the procedure does not interfere with other treatment alternatives. There is no consensus on laser settings. The lack of consistent use in evaluating vocal outcomes, whether objective or subjective, prevents the comparability between studies. The 585 nm pulsed dye laser appears to be an effective and safe therapeutic option in patients with non-malignant laryngeal pathology. Future controlled studies are needed to compare the 585 nm pulsed dye laser with other lasers or cold instrument procedures.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 10 ( 2023-10-09), p. 1477-
    Abstract: The velopalatine sphincter is a muscular valve that creates a hermetic seal between the nasopharynx and the oropharynx. It guarantees phonation, swallowing, and breathing (forces expirations). In wind musicians, sphincter closure must be precise during sound generation. Its failure will cause velopharyngeal incompetence (VPI) and the end of professional success. The objective of this article was to conduct a state-of-art review of VPI in wind musicians with a systematic approach based on the PRISMA Statement. The etiology, epidemiology, clinic, diagnosis, and treatment of VPI in wind musicians were evaluated. The research was carried out in different databases (PubMed/MEDLINE, the Cochrane Library, Scielo) and through the Mergullador metasearch engine. A total of 20 publications were selected. VPI is a pathology that affects around one-third of wind musicians according to studies. It causes pharyngeal noises and nasal air emissions during performance. The main etiology seems to be the fatigue of the velopalatine sphincter muscles. The most used diagnostic techniques consist of clinical history, physical examination, and nasofibroscopy. There is no consensus among authors about therapeutic management. Future investigations are necessary to confirm that fatigue of velopalatine sphincter muscles and other factors that increase it are the main causes of VPI in wind musicians.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Medicines, MDPI AG, Vol. 6, No. 3 ( 2019-07-22), p. 77-
    Abstract: Carbon Dioxide transoral laser microsurgery represents a reliable option for the treatment of early glottic carcinoma (Tis–T2), with good functional and oncological outcomes, nowadays representing one of the main options in larynx preservation protocols. The development and improvement of laser devices means surgeons are able to use more precise instruments compared with classic cold dissection in laser-assisted phonosurgery. Secondary effects on voice, swallowing, or quality of life as well as complications have been well documented. Also, with the introduction of a new proposal for staging systems following the principle of the three-dimensional map of isoprognostic zones, the use of narrow-band imaging in clinical evaluation and intraoperative, and the implementation of diffusion-weighted magnetic resonance during preoperative evaluation, the development of new tools to improve surgical quality and preliminary reports regarding the use of carbon dioxide laser in transoral robotic surgery suggests an exciting future for this technique.
    Type of Medium: Online Resource
    ISSN: 2305-6320
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2777965-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Tomography, MDPI AG, Vol. 5, No. 1 ( 2019-03-01), p. 118-126
    Abstract: Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2857000-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Current Oncology, MDPI AG, Vol. 21, No. 1 ( 2013-11-07), p. 105-
    Type of Medium: Online Resource
    ISSN: 1718-7729 , 1198-0052
    Language: Unknown
    Publisher: MDPI AG
    Publication Date: 2013
    detail.hit.zdb_id: 2270777-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Agronomy, MDPI AG, Vol. 11, No. 2 ( 2021-02-01), p. 274-
    Abstract: Spain has ranked 6th on the harvested bean area and 8th in bean production in the European Union (EU). The soils of this area have mixed silt loam and sandy loam texture, with moderate clay content, neutral or acidic pH, rich in organic matter and low carbonate levels, providing beans with high water absorption capacity and better organoleptic qualities after cooking. Similar to other crops, it is attacked by some phytopathogens. Hitherto, chemical methods have been used to control these organisms. However, with the Reform of the Community Agrarian Policy in the EU, the number of authorized plant protection products has been reduced to prevail food security, as well as to be sustainable in the long term, giving priority to the non-chemical methods that use biological agents, such as Trichoderma. This study aimed to investigate the relative importance of various crop soil parameters in the adaptation of Trichoderma spp. autoclaved soils (AS) and natural soils (NS) from the Protected Geographical Indication (PGI) “Alubia La Bañeza—León” that were inoculated with Trichoderma velutinum T029 and T. harzianum T059 and incubated in a culture chamber at 25 °C for 15 days. Their development was determined by quantitative PCR. Twelve soil samples were selected and analyzed from the productive zones of Astorga, La Bañeza, La Cabrera, Esla-Campos and Páramo. Their physicochemical characteristics were different by zone, as the texture of soils ranged between sandy loam and silt loam and the pH between strongly acid and slightly alkaline, as well as the organic matter (OM) concentration between low and remarkably high. Total C and N concentrations and their ratio were between medium and high in most of the soils and the rest of the micronutrients had an acceptable concentration except for Paramo’s soil. Both Trichoderma species developed better in AS than in NS, T. velutinum T029 grew better with high levels of OM, total C, ratio C:N, P, K, Fe, and Zn than T. harzianum T059 in clay soils, with the highest values of cation exchange capacity (CEC), pH, Ca, Mg and Mn. These effects were validated by Canonical Correlation Analysis (CCA), texture, particularly clay concentration, OM, electrical conductivity (EC), and pH (physical parameters) and B and Cu (soil elements) are the main factors explaining the influence in the Trichoderma development. OM, EC, C:N ratio and Cu are the main soil characteristics that influence in T. velutinum T029 development and pH in the development of T. harzianum T059.
    Type of Medium: Online Resource
    ISSN: 2073-4395
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2607043-1
    SSG: 23
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Agriculture, MDPI AG, Vol. 13, No. 3 ( 2023-03-21), p. 720-
    Abstract: Fusarium genus is a wide host phytopathogen causing significant losses in multiple crops, including hops. There is limited information on the sustainable management of Fusarium spp. in hop fields. Trichoderma is an endophytic fungus used in agriculture as a biological control agent (BCA) and as a plant growth promoter. It has been used to antagonize Fusarium spp. in other crops. The objective of the current study was to identify indigenous hop field Trichoderma isolates with biocontrol and hop growth promotion capabilities. Three isolates of Fusarium and eleven autochthonous Trichoderma isolates collected from sustainable hop fields were evaluated in this work. Direct confrontation tests (the physical interaction between the pathogen and BCA and their competition for space and nutrient resources) and membrane tests (the capacity of the BCA to produce metabolites or enzymes through a cellophane film and inhibit the development of the pathogen) assessed the antagonism of these Trichoderma isolates against Fusarium culmorum, F. sambucinum, and F. oxysporum. A bioassay with hop plantlets inoculated with a spore suspension of Trichoderma was performed to assess its hop growth enhancement. T. hamatum (T311 and T324), T. virens T312, and T. gamsii T327 showed high growth inhibition of Fusarium spp. phytopathogens and high plant growth promotion. Native Trichoderma isolates from sustainable hop-producing soils have great potential as BCAs and hop growth promoters.
    Type of Medium: Online Resource
    ISSN: 2077-0472
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2651678-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages