Author: Lee, Gwo-Bin ; Tsai, Yi-Cheng ; Kang, Chieh-Yi ; Hsu, Keng-Fu ; Lin, Chang-Ni ; Lin, Chun-Hong ; Hsu, Pang-Hung ; Hsu, Ching-Cheng ; Wu, Yi-Ying ; Liang, Yu-Ling

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment.

01 Dec 2019·Veterinary researchQ2 · AGRICULTURAL & FORESTRY SCIENCE

HutZ is required for biofilm formation and contributes to the pathogenicity of Edwardsiella piscicida

Q2 · AGRICULTURAL & FORESTRY SCIENCE

ArticleOA

Author: Shi, Yan-Jie ; Gong, Chun-Guang ; Huang, Hui-Qin ; Fang, Qing-Jian ; Hu, Yong-Hua

Abstract:

Edwardsiella piscicidais a severe fish pathogen. Haem utilization systems play an important role in bacterial adversity adaptation and pathogenicity. In this study, a speculative haem utilization protein, HutZEp, was characterized inE. piscicida.hutZEpis encoded with two other genes,hutWandhutX, in an operon that is similar to the haem utilization operonhutWXZidentified inV. cholerae. However, protein activity analysis showed that HutZEpis probably not related to hemin utilization. To explore the biological role of HutZEp, a markerlesshutZEpin-frame mutant strain, TX01ΔhutZ, was constructed. Deletion ofhutZEpdid not significantly affect bacterial growth in normal medium, in iron-deficient conditions, or in the presence of haem but significantly retarded bacterial biofilm growth. The expression of known genes related to biofilm growth was not affected byhutZEpdeletion, which indicated that HutZEpwas probably a novel factor promoting biofilm formation inE. piscicida. Compared to the wild-type TX01, TX01ΔhutZexhibited markedly compromised tolerance to acid stress and host serum stress. Pathogenicity analysis showed that inactivation ofhutZEpsignificantly impaired the ability ofE. piscicidato invade and reproduce in host cells and to infect host tissue. In contrast to TX01, TX01ΔhutZwas defective in blocking host macrophage activation. The expression ofhutZEpwas directly regulated by the ferric uptake regulator Fur. This study is the first functional characterization of HutZ in a fish pathogen, and these findings suggested that HutZEpis essential forE. piscicidabiofilm formation and contributes to host infection.

01 Dec 2019·Fish & shellfish immunologyQ2 · AGRICULTURAL & FORESTRY SCIENCE

Universal stress proteins contribute Edwardsiella piscicida adversity resistance and pathogenicity and promote blocking host immune response

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Shi, Yan-Jie ; Han, Yue-Xin ; Huang, Hui-Qin ; Fang, Qing-Jian ; Hu, Yong-Hua ; Fang, Zai-Guang

Universal stress proteins (Usps) exist ubiquitously in bacteria and other organisms. Usps play an important role in adaptation of bacteria to a variety of environmental stresses. There is increasing evidence that Usps facilitate pathogens to adapt host environment and are involved in pathogenicity. Edwardsiella piscicida (formerly included in E. tarda) is a severe fish pathogen and infects various important economic fish including tilapia (Oreochromis niloticus). In E. piscicida, a number of systems and factors that are involved in stress resistance and pathogenesis were identified. However, the function of Usps in E. piscicida is totally unknown. In this study, we examined the expressions of 13 usp genes in E. piscicida and found that most of these usp genes were up-regulated expression under high temperature, oxidative stress, acid stress, and host serum stress. Particularly, among these usp genes, usp13, exhibited dramatically high expression level upon several stress conditions. To investigate the biological role of usp13, a markerless usp13 in-frame mutant strain, TX01Δusp13, was constructed. Compared to the wild type TX01, TX01Δusp13 exhibited markedly compromised tolerance to high temperature, hydrogen peroxide, and low pH. Deletion of usp13 significantly retarded bacterial biofilm growth and decreased resistance against serum killing. Pathogenicity analysis showed that the inactivation of usp13 significantly impaired the ability of E. piscicida to invade into host cell and infect host tissue. Introduction of a trans-expressed usp13 gene restored the lost virulence of TX01Δusp13. In support of these results, host immune response induced by TX01 and TX01Δusp13 was examined, and the results showed reactive oxygen species (ROS) levels in TX01Δusp13-infected macrophages were significantly higher than those in TX01-infected cells. The expression level of several cytokines (IL-6, IL-8, IL-10, TNF-α, and CC2) in TX01Δusp13-infected fish was significantly higher than that in TX01-infected fish. These results suggested that the deletion of usp13 attenuated the ability of bacteria to overcome the host immune response to pathogen infection. Taken together, our study indicated Usp13 of E. piscicida was not only important participant in adversity resistance, but also was essential for E. piscicida pathogenicity and contributed to block host immune response to pathogen infection.

News (Medical) associated with Filgrastim-txid

17 Dec 2024

·www.accesswire.com

Theranexus and Exeltis (Insud Pharma) Announce Licensing Agreement to Commercialize Theranexus Tx01 for Two Rare Neurological Disorders

Exeltis will be granted an exclusive license to market and distribute Theranexus' novel formulation TX01 for the treatment of two rare neurological diseases notably in Europe.Theranexus will be eligible to receive up-front payment, development and commercial milestones and double-digit royalties on net sales. LYON, FRANCE and MADRID, SPAIN / ACCESSWIRE / December 17, 2024 / Theranexus, a biopharmaceutical company innovating in the treatment of rare neurological diseases, and Exeltis, a global pharmaceutical company and part of the Insud Pharma group, are pleased to announce the execution of a license and supply agreement to commercialize Theranexus' TX01, a novel formulation of a compound already approved in the indication for the treatment of rare neurological diseases.Under the terms of the agreement, Exeltis will acquire exclusive rights to market and distribute Theranexus' proprietary product across key regions, including the European Union, UK, Latin America, and selected Middle Eastern countries. This collaboration will target both Gaucher and Niemann-Pick type C diseases. The agreement includes a 2 M€ upfront payment to Theranexus and aggregated development and commercial milestone payments. Theranexus will also receive tiered double-digit royalties on Exeltis' net sales, reflecting the anticipated growth and impact of this novel therapeutic approach. Whole or part of the upfront and development milestones already paid at that time may be refunded to Exeltis should Theranexus not provide the documentation to support filing of a market approval application by October 31st, 2025.This partnership underscores the complementarity of expertise between Theranexus, with its specialized drug development capabilities, and Exeltis / Insud Pharma group - a global pharmaceutical company with €2.2 bn sales revenues and direct presence in 44 countries worldwide, whose extensive market reach and regulatory experience are instrumental in bringing similar innovative treatments to patients worldwide.Mathieu Charvériat, Chairman and CEO of Theranexus, commented: "Our agreement with Exeltis marks a significant milestone in the development of Theranexus, a validation of our strategic focus on rare neurological disorders and a confirmation of the value of our assets. Exeltis' global infrastructure and deep market knowledge make them an ideal partner to maximize the impact of our innovative formulation."Salustiano Perez, CEO of Exeltis, adds: "We are thrilled to join forces with Theranexus and leverage our commercial capabilities to bring this much-needed therapy to patients globally. This partnership aligns with Exeltis' mission to enhance patient care by broadening access to life-changing treatments."Julien Veys, Chief Business Officer at Theranexus, concludes: "We are delighted to build this alliance with the Exeltis team, addressing the needs of an underserved patient population. With an addressable market exceeding €200 million globally and a formulation tailored for a specific segment of rare disease patients, this partnership reflects our shared commitment to advancing therapeutic innovation and improving patient outcomes.About TheranexusTheranexus is an innovative biopharmaceutical company that emerged from the French Alternative Energies and Atomic Energy Commission (CEA). The company has a unique platform for the identification and characterization of advanced therapy drug candidates targeting rare neurological disorders and an initial drug candidate in clinical development for Batten disease. Theranexus is listed on the Euronext Growth market in Paris (FR0013286259- ALTHX).About Insud Pharma groupInsud Pharma is a pharmaceutical group with more than 45 years of history, presence in around 50 countries, 9,000 employees worldwide and 20 manufacturing facilities. Insud Pharma operates along the entire value chain of the pharmaceutical industry, offering expertise in scientific research, development, manufacturing, sales and marketing of a wide range of active pharmaceutical ingredients (APIs), finished dosage forms (FDFs) and branded pharmaceuticals for human and animal care, as well as biopharmaceuticals. Insud Pharma seeks to improve health worldwide by providing accessible, effective, safe and quality drug treatments through its different business units, with continuous investment in R&D and the latest technology. Through its brand Exeltis, Insud Pharma occupies a leading position in Women Health Care and it's a key player in Central Nervous System therapies.For more information: http://www.theranexus.comFollow us on Twitter and LinkedIn:Contacts:THERANEXUSChristine PLACETChief Financial Officer[email protected]FP2COMFlorence PORTEJOIEMedias Relations+ 33 (0)6 07 76 82 83[email protected]SOURCE: Theranexus

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100 Deals associated with Filgrastim-txid

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KEGG	Wiki	ATC	Drug Bank
-	Filgrastim-txid	L03AA02	DB00099

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Indication	Country/Location	Organization	Date
Acute Myeloid Leukemia	US	Tanvex BioPharma USA, Inc.	28 Jun 2024
Bone marrow depression	US	Tanvex BioPharma USA, Inc.	28 Jun 2024
Neutropenia	CA	Tanvex BioPharma USA, Inc.	01 Oct 2021

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