Novel Tyrosine Kinase Targets in Urothelial Carcinoma

International journal of molecular sciences

2021 Jan 13

Torres-Jiménez, J;Albarrán-Fernández, V;Pozas, J;Román-Gil, MS;Esteban-Villarrubia, J;Carrato, A;Rosero, A;Grande, E;Alonso-Gordoa, T;Molina-Cerrillo, J;
PMID: 33451055 | DOI: 10.3390/ijms22020747

Urothelial carcinoma represents one of the most prevalent types of cancer worldwide, and its incidence is expected to grow. Although the treatment of the advanced disease was based on chemotherapy for decades, the developments of different therapies, such as immune checkpoint inhibitors, antibody drug conjugates and tyrosine kinase inhibitors, are revolutionizing the therapeutic landscape of this tumor. This development coincides with the increasing knowledge of the pathogenesis and genetic alterations in urothelial carcinoma, from the non-muscle invasive setting to the metastatic one. The purpose of this article is to provide a comprehensive review of the different tyrosine kinase targets and their roles in the therapeutic scene of urothelial carcinoma.

Coordination between Transport and Local Translation in Neurons

Trends in Cell Biology

2021 Jan 01

Broix, L;Turchetto, S;Nguyen, L;
| DOI: 10.1016/j.tcb.2021.01.001

The axonal microtubules (MTs) support long-distance transport of cargoes that are dispatched to distinct cellular subcompartments. Among them, mRNAs are directly transported in membraneless ribonucleoprotein (RNP) granules that, together with ribosomes, can also hitchhike on fast-moving membrane-bound organelles for accurate transport along MTs. These organelles serve as platforms for mRNA translation, thus generating axonal foci of newly synthesized proteins. Local translation along axons not only supports MT network integrity but also modulates the processivity and function of molecular motors to allow proper trafficking of cargoes along MTs. Thus, identifying the mechanisms that coordinate axonal transport with local protein synthesis will shed new light on the processes underlying axon development and maintenance, whose deregulation often contribute to neurological disorders.

Analysis of mitochondrial double-stranded RNAs in human cells

STAR Protocols

2023 Mar 01

Kim, S;Yoon, J;Lee, K;Kim, Y;
| DOI: 10.1016/j.xpro.2022.102007

Human mitochondrial genome is transcribed bidirectionally, generating long complementary RNAs that can form double-stranded RNAs (mt-dsRNAs). When released to the cytosol, these mt-dsRNAs can activate antiviral signaling. Here, we present a detailed protocol for the analysis of mt-dsRNA expression. The protocol provides three approaches that can complement one another in examining mt-dsRNAs. While the described protocol is optimized for human cells, this approach can be adapted for use in other animal cell lines and tissue samples. For complete details on the use and execution of this protocol, please refer to Kim et al. (2022).1

Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex

International journal of molecular sciences

2022 Nov 19

Abou Nader, N;Zamberlam, G;Boyer, A;
PMID: 36430866 | DOI: 10.3390/ijms232214388

The cortex of the adrenal gland is organized into concentric zones that produce distinct steroid hormones essential for body homeostasis in mammals. Mechanisms leading to the development, zonation and maintenance of the adrenal cortex are complex and have been studied since the 1800s. However, the advent of genetic manipulation and transgenic mouse models over the past 30 years has revolutionized our understanding of these mechanisms. This review lists and details the distinct Cre recombinase mouse strains available to study the adrenal cortex, and the remarkable progress total and conditional knockout mouse models have enabled us to make in our understanding of the molecular mechanisms regulating the development and maintenance of the adrenal cortex.

Non-Human Primate Models of HIV Brain Infection and Cognitive Disorders

Viruses

2022 Sep 09

Byrnes, SJ;Angelovich, TA;Busman-Sahay, K;Cochrane, CR;Roche, M;Estes, JD;Churchill, MJ;
PMID: 36146803 | DOI: 10.3390/v14091997

Human Immunodeficiency virus (HIV)-associated neurocognitive disorders are a major burden for people living with HIV whose viremia is stably suppressed with antiretroviral therapy. The pathogenesis of disease is likely multifaceted, with contributions from viral reservoirs including the brain, chronic and systemic inflammation, and traditional risk factors including drug use. Elucidating the effects of each element on disease pathogenesis is near impossible in human clinical or ex vivo studies, facilitating the need for robust and accurate non-human primate models. In this review, we describe the major non-human primate models of neuroHIV infection, their use to study the acute, chronic, and virally suppressed infection of the brain, and novel therapies targeting brain reservoirs and inflammation.

Double Immunohistochemical Staining on Formalin-Fixed Paraffin-Embedded Tissue Samples to Study Vascular Co-option

Methods in molecular biology (Clifton, N.J.)

2022 Sep 26

Annese, T;Errede, M;De Giorgis, M;Lorusso, L;Tamma, R;Ribatti, D;
PMID: 36161411 | DOI: 10.1007/978-1-0716-2703-7_8

Vascular co-option is a non-angiogenic mechanism whereby tumor growth and progression move on by hijacking the pre-existing and nonmalignant blood vessels and is employed by various tumors to grow and metastasize.The histopathological identification of co-opted blood vessels is complex, and no specific markers were defined, but it is critical to develop new and possibly more effective therapeutic strategies. Here, in glioblastoma, we show that the co-opted blood vessels can be identified, by double immunohistochemical staining, as weak CD31+ vessels with reduced P-gp expression and proliferation and surrounded by highly proliferating and P-gp- or S100A10-expressing tumor cells. Results can be quantified by the Aperio Colocalization algorithm, which is a valid and robust method to handle and investigate large data sets.

Targeting Alternative Splicing for Therapeutic Interventions

Methods in molecular biology (Clifton, N.J.)

2022 Jul 27

Centa, JL;Hastings, ML;
PMID: 35895256 | DOI: 10.1007/978-1-0716-2521-7_2

Targeting of pre-mRNA splicing has yielded a rich variety of strategies for altering gene expression as a treatment for disease. The search for therapeutics that can modulate splicing has been dominated by antisense oligonucleotides (ASOs) and small molecule compounds, with each platform achieving remarkably effective results in the clinic. The success of RNA-targeting drugs has led to the exploration of new strategies to expand the repertoire of this type of therapeutic. Here, we discuss some of the more common causes of faulty gene expression and provide examples of approaches that have been developed to target and correct these defects for therapeutic value.

Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

Neuron

2022 Feb 19

Harbauer, AB;Hees, JT;Wanderoy, S;Segura, I;Gibbs, W;Cheng, Y;Ordonez, M;Cai, Z;Cartoni, R;Ashrafi, G;Wang, C;Perocchi, F;He, Z;Schwarz, TL;
PMID: 35216662 | DOI: 10.1016/j.neuron.2022.01.035

PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for the local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for the activation of mitophagy.

Immune landscape of human placental villi using single-cell analysis

Development (Cambridge, England)

2022 Jan 20

Toothaker, JM;Olaloye, O;McCourt, BT;McCourt, CC;Silva, TN;Case, RM;Liu, P;Yimlamai, D;Tseng, G;Konnikova, L;
PMID: 35050308 | DOI: 10.1242/dev.200013

Maintenance of healthy pregnancy is reliant on successful balance between the fetal and maternal immune systems. Although maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, though rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined T cells isolated from PV samples may be more proliferative than adult T cells at baseline after T cell receptor (TCR) stimulation. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells.

Developmental, Physiological, and Functional Neurobiology of the Inner Ear

Neuromethods

2022 Jan 03

Groves, AK;
| DOI: 10.1007/978-1-0716-2022-9

We use cookies to make sure that our website works properly, as well as some ‘optional’ cookies to personalise content and advertising, provide social media features and analyse how people use our site. By accepting some or all optional cookies you give consent to the processing of your personal data, including transfer to third parties, some in countries outside of the European Economic Area that do not offer the same data protection standards as the country where you live. You can decide which optional cookies to accept by clicking on ‘Manage Settings’, where you can also find more information about how your personal data is processed. Further information can be found in our privacy policy [https://link.springer.com/privacystatement].

Cyclical fate restriction: a new view of neural crest cell fate specification

Development

2021 Nov 15

Kelsh, R;Camargo Sosa, K;Farjami, S;Makeev, V;Dawes, J;Rocco, A;
| DOI: 10.1242/dev.176057

Neural crest cells are crucial in development, not least because of their remarkable multipotency. Early findings stimulated two hypotheses for how fate specification and commitment from fully multipotent neural crest cells might occur, progressive fate restriction (PFR) and direct fate restriction, differing in whether partially restricted intermediates were involved. Initially hotly debated, they remain unreconciled, although PFR has become favoured. However, testing of a PFR hypothesis of zebrafish pigment cell development refutes this view. We propose a novel ‘cyclical fate restriction’ hypothesis, based upon a more dynamic view of transcriptional states, reconciling the experimental evidence underpinning the traditional hypotheses.

The rostromedial tegmental (RMTg) \"brake\" on dopamine and behavior: A decade of progress but also much unfinished work

Neuropharmacology

2021 Aug 22

Jhou, T;
PMID: 34433088 | DOI: 10.1016/j.neuropharm.2021.108763

Between 2005-2009, several research groups identified a strikingly dense inhibitory input to midbrain dopamine neurons in a previously uncharted region posterior to the ventral tegmental area (VTA). This region is now denoted as either the rostromedial tegmental nucleus (RMTg) or the "tail of the VTA" (tVTA), and is recognized to express distinct genetic markers, encode negative "prediction errors" (inverse to dopamine neurons), and play critical roles in behavioral inhibition and punishment learning. RMTg neurons are also influenced by many categories of abused drugs, and may drive some aversive responses to such drugs, particularly cocaine and alcohol. However, despite much progress, many important questions remain about RMTg molecular/genetic properties, diversity of projection targets, and applications to addiction, depression, and other neuropsychiatric disorders.

Pages

	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

Search form

Probes for INS

Content for comparison

Gene

Product

Research area

Category

Pages

Advanced Cell Diagnostics

Bio-Techne

Advanced Cell Diagnostics China