A Sing-Arm, Open Clinical Pharmacology Study of Intravenous injection with or without Intratumoral injection of Oncolytic Virus Injection (RT-01) in Patients With Advanced Solid Tumors

Start Date18 Jan 2022

Sponsor / Collaborator

First Affiliated Hospital Bengbu Medical College

NCT05122572 / Unknown statusPhase 1IIT

An Open-label Clinical Study to Evaluate the Safety and Efficacy of Intravenous With and Without Intratumoral Oncolytic Virus Injection (RT-01) Combined With or Without Immune Checkpoint Inhibitors (Nivolumab) in the Treatment of Patients With Advanced Solid Tumors

This is a single-arm, open-lable study to determine the safety, tolerability and preliminary efficacy of oncolytic virus injection (RT-01) combined with or without immune checkpoint inhibitors (Nivolumab) in the treatment of patients with advanced solid tumors.

Start Date01 Nov 2021

Sponsor / Collaborator

Wuxi People's Hospital

100 Clinical Results associated with RT-01

100 Translational Medicine associated with RT-01

100 Patents (Medical) associated with RT-01

Literatures (Medical) associated with RT-01

01 Aug 2022·Journal of Controlled Release

Mitochondria-targeted hydrogen sulfide donors versus acute oxidative gastric mucosal injury

Article

Author: Wójcik-Grzybek, Dagmara ; Bakalarz, Dominik ; Magierowski, Marcin ; Torregrossa, Roberta ; Sliwowski, Zbigniew ; Korbut, Edyta ; Whiteman, Matthew ; Cieszkowski, Jakub ; Magierowska, Katarzyna ; Szetela, Małgorzata

Hydrogen sulfide (H₂S) as a gaseous molecule prevents gastrointestinal (GI)-tract against various injuries. This study aimed to evaluate for the first time the detailed molecular mechanism of mitochondria-targeting H₂S-prodrugs, AP39 and RT01 in gastroprotection against ischemia/reperfusion (I/R)-induced lesions. Wistar rats exposed to I/R were pretreated i.g. with vehicle, AP39 (0.004-2 mg/kg), RT01 (0.1 mg/kg), or with AP219 (0.1 mg/kg) as structural control without ability to release H₂S. AP39 was also administered with mTOR1 inhibitor, rapamycin (1 mg/kg i.g.). Gastric damage area was assessed micro-/macroscopically, gastric blood flow (GBF) by laser flowmetry, mRNA level of HIF-1α, GPx, SOD1, SOD2, annexin-A1, SOCS3, IL-1RA, IL-1β, IL-1R1, IL-1R2, TNFR2, iNOS by real-time PCR. Gastric mucosal and/or serum content of IL-1β, IL-4, IL-5, IL-10, G-CSF, M-CSF, VEGFA, GRO, RANTES, MIP-1α, MCP1, TNF-α, TIMP1, FABP3, GST-α, STAT3/5 and phosphorylation of mTOR, NF-κB, ERK, Akt was evaluated by microbeads-fluorescent assay. Mitochondrial complexes activities were measured biochemically. RNA damage was assessed as 8-OHG by ELISA. AP39 and RT01 reduced micro-/macroscopic gastric I/R-injury increasing GBF. AP39-gastroprotection was accompanied by maintained activity of mitochondrial complexes, prevented RNA oxidation and enhanced mRNA/protein expression of SOCS3, IL-1RA, annexin-A1, GST-α, HIF-1α. Rapamycin reversed AP-39-gastroprotection. AP39-gastroprotection was followed by decreased NF-κB, ERK, IL-1β and enhanced Akt and mTOR proteins phosphorylation. AP39-prevented gastric mucosal damage caused by I/R-injury, partly by mitochondrial complex activity maintenance. AP39-mediated attenuation of gastric mucosal oxidation, hypoxia and inflammation involved mTOR1 and Akt pathways activity and modulation of HIF-1α, GST-α, SOCS3, IL1RA and TIMP1 molecular interplay.

19 Jul 2018·AgingQ3 · MEDICINE

Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2

Q3 · MEDICINE

Article

Author: Latorre, Eva ; Torregrossa, Roberta ; Whiteman, Matthew ; Harries, Lorna W. ; Wood, Mark E.

Cellular senescence is a key driver of ageing, influenced by age-related changes to the regulation of alternative splicing. Hydrogen sulfide (H₂S) has similarly been described to influence senescence, but the pathways by which it accomplishes this are unclear.We assessed the effects of the slow release H₂S donor Na-GYY4137 (100 µg/ml), and three novel mitochondria-targeted H₂S donors AP39, AP123 and RT01 (10 ng/ml) on splicing factor expression, cell proliferation, apoptosis, DNA replication, DNA damage, telomere length and senescence-related secretory complex (SASP) expression in senescent primary human endothelial cells.All H₂S donors produced up to a 50% drop in senescent cell load assessed at the biochemical and molecular level. Some changes were noted in the composition of senescence-related secretory complex (SASP); IL8 levels increased by 24% but proliferation was not re-established in the culture as a whole. Telomere length, apoptotic index and the extent of DNA damage were unaffected. Differential effects on splicing factor expression were observed depending on the intracellular targeting of the H₂S donors. Na-GYY4137 produced a general 1.9 - 3.2-fold upregulation of splicing factor expression, whereas the mitochondria-targeted donors produced a specific 2.5 and 3.1-fold upregulation of SRSF2 and HNRNPD splicing factors only. Knockdown of SRSF2 or HNRNPD genes in treated cells rendered the cells non-responsive to H₂S, and increased levels of senescence by up to 25% in untreated cells.Our data suggest that SRSF2 and HNRNPD may be implicated in endothelial cell senescence, and can be targeted by exogenous H₂S. These molecules may have potential as moderators of splicing factor expression and senescence phenotypes.

01 Jun 2012·Radiotherapy and OncologyQ2 · MEDICINE

The dose–response of the anal sphincter region – An analysis of data from the MRC RT01 trial

Q2 · MEDICINE

Article

Author: Florian Buettner ; Sarah L. Gulliford ; Steve Webb ; Matthew R. Sydes ; David P. Dearnaley ; Mike Partridge

PURPOSEMost studies investigating the dose-response of the rectum focus on rectal bleeding. However, it has been reported that other symptoms such as urgency or sphincter control have a large impact on quality-of-life and that different symptoms are related to the dose to different parts of the anorectal wall. In this study correlations between the 3D dose distribution to the anal-sphincter region and radiation-induced side-effects were quantified.MATERIALS AND METHODSDose-surface maps of the anal canal were generated. Next, longitudinal and lateral extent and eccentricity were calculated at different dose levels; DSHs and DVHs were also determined. Correlations between these dosimetric measures and seven clinically relevant endpoints were determined by assessing dosimetric constraints. Furthermore, an LKB model was generated. The study was performed using the data of 388 prostate patients from the RT01 trial (ISRCTN 47772397).RESULTSSubjective sphincter control was significantly correlated with the dose to the anal surface. The strongest correlations were found for lateral extent at 53 Gy (p=0.01). Outcome was also significantly correlated with the DSH and the mean dose to the anal surface.CONCLUSIONSThe dose to the anal sphincter region should be taken into account when generating treatment-plans. This could be done using shape-based tools, DSH/DVH-based tools or an NTCP model.

100 Deals associated with RT-01

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 1	CN	Wuxi People's Hospital	01 Nov 2021
Advanced Malignant Solid Neoplasm	Phase 1	CN	Wuxi People's Hospital	01 Nov 2021

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