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Programmed cell death along the midline axis patterns ipsilaterality in gastrulation.

ABSTRACT: Bilateral symmetry is the predominant body plan in the animal kingdom. Cells on the left and right sides remain compartmentalized on their ipsilateral side throughout life, but with occasional variation, as evidenced by gynandromorphs and human disorders. How this evolutionarily conserved body plan is programmed remains a fundamental yet unanswered question. Here, we show that germ-layer patterning in avian gastrulation is ipsilateral despite cells undergoing highly invasive mesenchymal transformation and cell migration. Contralateral invasion is suppressed by extracellular matrix (ECM) and programmed cell death (PCD) along the embryonic midline. Ipsilateral gastrulation was lost by midline ECM and PCD inhibition but restored with exogenously induced PCD. Our data support ipsilaterality as an integral component of bilaterality and highlight a positive functional role of PCD in development.

SUBMITTER: Maya-Ramos L

PROVIDER: S-EPMC7017582 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Programmed cell death along the midline axis patterns ipsilaterality in gastrulation.

Maya-Ramos Lisandro L Mikawa Takashi T

Science (New York, N.Y.) 20200101 6474

Bilateral symmetry is the predominant body plan in the animal kingdom. Cells on the left and right sides remain compartmentalized on their ipsilateral side throughout life, but with occasional variation, as evidenced by gynandromorphs and human disorders. How this evolutionarily conserved body plan is programmed remains a fundamental yet unanswered question. Here, we show that germ-layer patterning in avian gastrulation is ipsilateral despite cells undergoing highly invasive mesenchymal transfor ...[more]

PMID: 31919222

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Project description:IntroductionThe clinical successes seen with anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors.MethodsWe identified clinical trials involving anti-PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials.ResultsWe found 686 clinical trials investigating anti-PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration's approval of an anti-PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy.ConclusionsThe number of clinical trials investigating anti-PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.

Dataset Information

Programmed cell death along the midline axis patterns ipsilaterality in gastrulation.

Publications

Programmed cell death along the midline axis patterns ipsilaterality in gastrulation.

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