Modified mesoporous silica nanocarriers containing superparamagnetic iron oxide nanoparticle, 5-fluorouracil or oxaliplatin, and metformin as a radiosensitizer, significantly impact colorectal cancer radiation therapy

Article

作者: Matin, Maryam M ; Bahrami, Ahmad Reza ; Khalili-Hezarjaribi, Hojjat ; Sh. Saljooghi, Amir ; Reza Bahrami, Ahmad ; Matin, Maryam M. ; Sh Saljooghi, Amir

This study investigates the anticancer effects of SPION-based silica nanoparticles carrying 5-fluorouracil (5-FU) or oxaliplatin (OX), and metformin (MET) on colorectal cancer cells. Nanocarriers were equipped with pH-responsive gold gatekeepers for controlled release, PEGylation for longer circulation, and folic acid (FA) for targeted delivery. The effects were evaluated by investigating cell viability, cellular uptake, flow cytometry, and clonogenic assay in vitro. The efficacy of the system was also tested in vivo on C57BL/6 mice bearing HT-29 tumors, and potential side effects were evaluated. Nanocarriers were synthesized with hydrodynamic diameters of 79.8 nm for 5-FU and 85.2 nm for OX; zeta potentials of -21 and -22 mV, respectively, and remained stable after 72 h. Encapsulation efficiencies were 85 % for 5-FU, 80 % for OX, and 83 % for MET, with loading capacities of 44 %, 38 %, and 41 %, respectively. Drug release in acidic buffer was 38.7 % for 5-FU, 32.8 % for OX, and 43.5 % for MET. MTT assay showed increased toxicity due to FA conjugation, while PEGylation reduced the hemolysis activity. Targeted nanocarriers demonstrated superior cellular uptake and tumor localization compared to non-targeted variants. The combination of 5-FU-MET and OX-MET nanocarriers with radiation therapy (RT) demonstrated the greatest effect on their antitumor activity, accompanied by minimal side effects indicating effective tumor targeting in vivo. MRI and CT imaging further supported these findings. This study underscores the synergistic impact of MET alongside RT on the inhibition of cancer cells and tumor growth for both targeted 5-FU and OX nanocarriers reflecting the significant radiosensitizing properties of MET.

2023-07-01·Chemosphere

Global ocean contamination of per- and polyfluoroalkyl substances: A review of seabird exposure

Review

作者: Sun, Jiachen ; Chu, Jiansong ; Xing, Lingling

Per- and polyfluoroalkyl substances (PFAS) have been extensively produced and used as surfactants and repellents for decades. To date, the global contamination pattern of PFAS in marine biota has seldomly been reviewed. Seabirds are ideal biomonitoring tools to study environmental contaminants and their effects. Here, we compiled and synthesized reported PFAS concentrations in various seabird species to reflect spatiotemporal patterns and exposure risks of major PFAS on a global ocean scale. Perfluorooctane sulfonic acid (PFOS) was the most studied PFAS in seabirds, which showed the highest level in eggs of common guillemots (U. aalge) from the Baltic Sea, followed by great cormorants (P. carbo) from the North Sea and double-crested cormorants (P.auritus) from the San Francisco Bay, whereas the lowest were those reported for Antarctic seabirds. The temporal pattern showed an overall higher level of PFOS in the late 1990s and early 2000s, consistent with the phase-out of perfluorooctane sulfonyl fluoride-based products. Maximum liver PFOS concentrations in several species such as cormorants and fulmars from Europe and North America exceeded the estimated toxicity reference values. Systematic evaluations using representative species and long time-series are necessary to understand contamination patterns in seabirds in South America, Africa, and Asia where information is lacking. In addition, limited research has been conducted on the identification and toxic effects of novel substitutes such as fluorotelomers and ether PFAS (F-53B, Gen-X etc.) in seabirds. Further research, including multi-omics analysis, is needed to comprehensively characterize the exposure and toxicological profiles of PFAS in seabirds and other wildlife.

2023-07-01·Ecotoxicology and environmental safety

Exposure to PFOA and its novel analogs disrupts lipid metabolism in zebrafish

Article

作者: Qiao, Ying ; Zhang, Xuemin ; Wang, Li ; Sun, Weiqiang ; Liu, Hui ; Griffin, Nathan ; Zhang, Hongxia

Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC₅₀ (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC₅₀ toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.

项与 MET-X 相关的新闻（医药）

2023-04-27

·PRNewswire

MEDIVIR AB - INTERIM REPORT JANUARY - MARCH 2023

HUDDINGE, Sweden, April 27, 2023 /PRNewswire/ -- "Thanks to the strong interest from clinicians and patients, we were able to swiftly dose the first patients in the phase 2a part of the combination study with fostrox and Lenvima® in HCC after completed dose escalation" January – March Financial summary for the quarter Net turnover amounted to SEK 0.4 (0.5) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -18.9 (-31.4) million. Basic and diluted earnings per share amounted to SEK -0.34 (-0.59) and SEK -0.34 (-0.59) respectively. Cash flow from operating activities amounted to SEK -16.1 (-39.9) million. Cash and cash equivalents at the end of the period amounted to SEK 100.8 (180.8) million. Significant events during the quarter In January, Medivir's partner Infex Therapeutics received Qualified Infectious Disease Product (QIDP) designation from the FDA for MET-X. In February, it was announced that the recommended dose (RP2D) for the first combination arm of the phase 2a part of the fostrox study was established at 30 mg for fostrox in combination with Lenvima®. In February, Pia Baumann took over as CMO at Medivir. In March, it was announced that the first patient had been dosed in the phase 2a part of Medivir's study with fostrox in combination with Lenvima®. In March, it was announced that Medivir's nomination committee to the 2023 annual general meeting proposes a board consisting of current members Uli Hacksell, Lennart Hansson, Yilmaz Mahshid, Anette Lindqvist and Bengt Westermark. The nomination committee also proposes re-election of Uli Hacksell as chairman of the board. Events after the end of the period In April, new data were presented showing synergistic anti-tumor effect of fostrox in triple combination with anti-PD1 and Lenvima® in non-clinical tumor models. Conference call for investors, analysts and the media The Interim Report January - March 2023 will be presented by Medivir's CEO, Jens Lindberg. Time: Thursday, April 27, 2023, at 15.00 (CET). For dial-in numbers to the conference call, please see information on the website; The conference call will also be streamed via a link on the website: The presentation will be available on Medivir's website after completion of the conference. CEO's message The first quarter of the year has been eventful in a very positive way for Medivir. In February, we were able to complete the dose escalation part and establish the recommended phase 2 dose for fostrox in combination with Lenvima® for patients with primary liver cancer. Shortly thereafter, the first patient was dosed in the phase 2a part of the combination study, where safety and signs of efficacy are further evaluated. We have also presented at the AACR in April new data on the synergistic anti-tumor effect of fostrox in triple combination with anti-PD1 and Lenvima® in non-clinical tumor models. The strong interest from both patients and clinicians in Medivir's combination study with fostrox confirms the great medical need for more effective treatments for patients with hepatocellular carcinoma (HCC). The interest in participating in the study has been very large and enabled us to complete the dose escalation part and shortly afterwards start the treatment of the first patient with HCC in the phase 2a part of the combination study with fostrox and Lenvima®. The preliminary results from the dose escalation part with fostrox in combination with Lenvima® were positive with a good safety and tolerability profile and no dose-limiting toxicity has been observed. The results from the dose escalation and expansion phase will form the basis of the future development plan for fostrox. Lenvima® is today established as standard treatment for second-line HCC. This means that the combination of fostrox and Lenvima® has clear potential to contribute to more patients in the second line getting an increased clinical benefit from their treatment. For the other combination arm where fostrox is given together with Keytruda®, the phase 1b part is still ongoing. We have also, after the end of the quarter, presented new data describing the potential for fostrox to enhance anti-tumor activity in a triple combination with anti-PD-1 and kinase inhibitors in non-clinical tumor models. In order for more patients to get a satisfactory effect from their treatment, new combination options with different mechanisms of action will be critical. These new data show a synergistic anti-tumor effect when these three different treatments are combined. Fostrox, with its unique, liver-targeted approach, opens up completely new combinations with three different approaches to effectively treat HCC. Pia Baumann has been in place since February as the new CMO at Medivir and her experiences will be very valuable for the continued clinical development of fostrox. Medivir's clinical project birinapant is out-licensed to IGM Biosciences, which is running a phase I clinical trial in solid tumors with birinapant in combination with its own DR5 agonist antibody IGM-8444. During the quarter, the fourth dose-escalation cohort was completed and no dose-limiting toxicity has been observed to date. IGM has started the dosing of a fifth cohort in the study. I would also like to mention our preclinical MBLI program aimed at addressing the threat of resistant bacteria. It is licensed to INFEX Therapeutics in England and MET-X, which is the name of the project, received QIDP classification by the FDA in January. INFEX has communicated its intention to initiate a phase 1 program in 2023. In summary, an eventful quarter with the clinical development of fostrox in focus. We hope and believe that fostrox can become an effective treatment against liver cancer that makes a real difference for the patients and for the care and thus also for our shareholders. I look forward to keeping you informed of Medivir's continued development. Jens Lindberg Chief Executive Officer For further information, please contact Magnus Christensen, CFO Phone: +46 (0)8 5468 3100 E-mail: [email protected] This report has not been subject to auditors' review. The information was submitted for publication at 08.30 CET on April 27, 2023. The following files are available for download: SOURCE Medivir

临床1期临床2期财报临床结果

2023-04-27

·BioSpace

Medivir AB - Interim Report January - March 2023

HUDDINGE, Sweden, April 27, 2023 /PRNewswire/ -- "Thanks to the strong interest from clinicians and patients, we were able to swiftly dose the first patients in the phase 2a part of the combination study with fostrox and Lenvima® in HCC after completed dose escalation" January – March Financial summary for the quarter Net turnover amounted to SEK 0.4 (0.5) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -18.9 (-31.4) million. Basic and diluted earnings per share amounted to SEK -0.34 (-0.59) and SEK -0.34 (-0.59) respectively. Cash flow from operating activities amounted to SEK -16.1 (-39.9) million. Cash and cash equivalents at the end of the period amounted to SEK 100.8 (180.8) million. Significant events during the quarter In January, Medivir's partner Infex Therapeutics received Qualified Infectious Disease Product (QIDP) designation from the FDA for MET-X. In February, it was announced that the recommended dose (RP2D) for the first combination arm of the phase 2a part of the fostrox study was established at 30 mg for fostrox in combination with Lenvima®. In February, Pia Baumann took over as CMO at Medivir. In March, it was announced that the first patient had been dosed in the phase 2a part of Medivir's study with fostrox in combination with Lenvima®. In March, it was announced that Medivir's nomination committee to the 2023 annual general meeting proposes a board consisting of current members Uli Hacksell, Lennart Hansson, Yilmaz Mahshid, Anette Lindqvist and Bengt Westermark. The nomination committee also proposes re-election of Uli Hacksell as chairman of the board. Events after the end of the period In April, new data were presented showing synergistic anti-tumor effect of fostrox in triple combination with anti-PD1 and Lenvima® in non-clinical tumor models. Conference call for investors, analysts and the media The Interim Report January - March 2023 will be presented by Medivir's CEO, Jens Lindberg. Time: Thursday, April 27, 2023, at 15.00 (CET). For dial-in numbers to the conference call, please see information on the website; The conference call will also be streamed via a link on the website: The presentation will be available on Medivir's website after completion of the conference. CEO's message The first quarter of the year has been eventful in a very positive way for Medivir. In February, we were able to complete the dose escalation part and establish the recommended phase 2 dose for fostrox in combination with Lenvima® for patients with primary liver cancer. Shortly thereafter, the first patient was dosed in the phase 2a part of the combination study, where safety and signs of efficacy are further evaluated. We have also presented at the AACR in April new data on the synergistic anti-tumor effect of fostrox in triple combination with anti-PD1 and Lenvima® in non-clinical tumor models. The strong interest from both patients and clinicians in Medivir's combination study with fostrox confirms the great medical need for more effective treatments for patients with hepatocellular carcinoma (HCC). The interest in participating in the study has been very large and enabled us to complete the dose escalation part and shortly afterwards start the treatment of the first patient with HCC in the phase 2a part of the combination study with fostrox and Lenvima®. The preliminary results from the dose escalation part with fostrox in combination with Lenvima® were positive with a good safety and tolerability pro no dose-limiting toxicity has been observed. The results from the dose escalation and expansion phase will form the basis of the future development plan for fostrox. Lenvima® is today established as standard treatment for second-line HCC. This means that the combination of fostrox and Lenvima® has clear potential to contribute to more patients in the second line getting an increased clinical benefit from their treatment. For the other combination arm where fostrox is given together with Keytruda®, the phase 1b part is still ongoing. We have also, after the end of the quarter, presented new data describing the potential for fostrox to enhance anti-tumor activity in a triple combination with anti-PD-1 and kinase inhibitors in non-clinical tumor models. In order for more patients to get a satisfactory effect from their treatment, new combination options with different mechanisms of action will be critical. These new data show a synergistic anti-tumor effect when these three different treatments are combined. Fostrox, with its unique, liver-targeted approach, opens up completely new combinations with three different approaches to effectively treat HCC. Pia Baumann has been in place since February as the new CMO at Medivir and her experiences will be very valuable for the continued clinical development of fostrox. Medivir's clinical project birinapant is out-licensed to IGM Biosciences, which is running a phase I clinical trial in solid tumors with birinapant in combination with its own DR5 agonist antibody IGM-8444. During the quarter, the fourth dose-escalation cohort was completed and no dose-limiting toxicity has been observed to date. IGM has started the dosing of a fifth cohort in the study. I would also like to mention our preclinical MBLI program aimed at addressing the threat of resistant bacteria. It is licensed to INFEX Therapeutics in England and MET-X, which is the name of the project, received QIDP classification by the FDA in January. INFEX has communicated its intention to initiate a phase 1 program in 2023. In summary, an eventful quarter with the clinical development of fostrox in focus. We hope and believe that fostrox can become an effective treatment against liver cancer that makes a real difference for the patients and for the care and thus also for our shareholders. I look forward to keeping you informed of Medivir's continued development. Jens Lindberg Chief Executive Officer For further information, please contact Magnus Christensen, CFO Phone: +46 (0)8 5468 3100 E-mail: magnus.christensen@medivir.com This report has not been subject to auditors' review. The information was submitted for publication at 08.30 CET on April 27, 2023. The following files are available for download: View original content: SOURCE Medivir Company Codes: Bloomberg:MVIRB@SS, ISIN:SE0000273294, RICS:MVIRB.ST, Stockholm:MVIRB

临床1期临床2期临床结果财报

2023-02-15

·BioSpace

Medivir AB - Year-End Report January - December 2022

HUDDINGE, Sweden, Feb. 15, 2023 /PRNewswire/ -- Continued strong recruitment in the dose escalation part of the fostrox study. October – December Financial summary for the quarter Net turnover amounted to SEK 2.3 (13.9) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -17.9 (-23.5) million. Basic and diluted earnings per share amounted to SEK -0.32 (-0.44) and SEK -0.32 (-0.44) respectively. Cash flow from operating activities amounted to SEK -24.7 (-5.4) million. Cash and cash equivalents at the end of the period amounted to SEK 117.4 (221.2) million. Significant events during the quarter In October the nomination committee was appointed ahead of the 2023 AGM. The Nomination Committee consists of Karl Tobieson (Chairman), appointed by Linc AB, Richard Torgerson, appointed by Nordea Investment Funds, Anders Hallberg, appointed by HealthInvest Partners and Uli Hacksell, Chairman of the Board, Medivir AB. Pia Baumann was recruited in November as new Chief Medical Officer, taking office in February 2023. Medivir presented new data, showing additive efficacy of fostrox in combination with anti-PD1 in experimental tumor models, at the SITC Immunotherapy Conference in November. Medivir completed a pre-IND meeting with the US Food and Drug Administration and received positive feedback on the development plan in preparation for an IND for its candidate drug fostrox. January – December Financial summary for the period Net turnover amounted to SEK 4.4 (25.5) million. The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -84.8 (-59.5) million. Basic and diluted earnings per share amounted to SEK -1.59 (-1.20) and SEK -1.59 (-1.20) respectively. Cash flow from operating activities amounted to SEK -101.8 (-48.7) million. Cash and cash equivalents at the end of the period amounted to SEK 117.4 (221.2) million. Significant events after the end of the period On January 11 it was announced that Medivir's partner Infex Therapeutics has been granted Qualified Infectious Disease Product (QIDP) designation by the U.S. Food and Drug Administration (FDA) for MET-X, the company's broad spectrum Metallo-beta-lactamase inhibitor (MBLI) based on Medivir's MBLI program. Conference call for investors, analysts and the media The Year-End Report January - December 2022 will be presented by Medivir's CEO, Jens Lindberg. Time: Wednesday, February 15, 2023, at 14.00 (CET). Phone numbers for participants from: Sweden + 46 8 505 163 86 Europe +44 20 3198 4884 US +1 412-317 6300 Pin code 1872625# The conference call will also be streamed via a link on the website: The presentation will be available on Medivir's website after completion of the conference. CEO's message Taking over as CEO of Medivir in January 2022, I was given the privilege of leading a great team to develop cancer medicines that can really make a difference. Our main focus in 2022 has been the continued clinical development of Medivir's proprietary candidate drug fostroxacitabine bralpamide (fostrox). Fostrox has the potential to become the first liver-targeted and orally administered drug that can help patients with various cancers of the liver. Its unique mechanism of action in liver cancer makes fostrox attractive to combine with several other drugs for the treatment of hepatocellular carcinoma HCC. The combination study is progressing as expected in ongoing dose escalation cohorts. The measures taken to accelerate patient recruitment at the end of the summer had the desired effect. Since then, interest in the study has been very high, with patients standing in line waiting for new cohorts to be opened. We look forward to shortly establishing the recommended dose for the first combination arm and subsequently initiating the phase 2a portion of the study. We have also presented new data for fostrox during the year. At the EASL Liver Cancer Summit in February, Medivir was able to present biomarker data from the phase 1 study with fostrox which, among other things, shows that fostrox provides a tumor-selective effect in the liver by causing the desired DNA damage and cell death in tumor cells in the liver but not in normal or healthy liver cells. At the SITC Immunotherapy Conference in November, Medivir presented new data showing that the combination of fostrox with anti-PD1 provides an improved effect in experimental tumor models and creates changes in the tumor microenvironment consistent with increased immune-mediated antitumor activity. It is also gratifying that we, at our pre-IND meeting with the US Food and Drug Administration FDA in December, received positive feedback on the IND preparation program for fostrox. We plan to submit an IND application to the US authority in 2023. In Medivir's business development, we focus on our two clinical projects for partnership, remetinostat and MIV-711. The data packages for both projects have been strengthened during the year and we continue our dialogues with external parties in order to find the best possible solution for each substance. Medivir's clinical project birinapant was out-licensed to IGM Biosciences in 2021. IGM is conducting ongoing clinical development work with the phase I clinical study in solid tumors with birinapant in combination with IGM's own DR5 agonist antibody IGM-8444. As of Q4 2022, IGM reported that the fourth dose-escalation cohort was ongoing and no dose-limiting toxicities were observed to date. Medivir's preclinical research program USP-1 was out-licensed in 2020 to US-based Tango Therapeutics, which announced that it has selected TNG348, a USP-1 inhibitor from this research program, as a development/drug candidate in the treatment of BRCA1/2 mutated cancers. Tango intends to open an IND in the US in 2023 for TNG348. Also our preclinical program MBLI aimed at addressing the threat of resistant bacteria appears to be moving towards clinical development. It is licensed to INFEX Therapeutics in England, which recently received QIDP-designation from the FDA and communicated its intention to initiate a phase 1 program in 2023. I would like to take this opportunity to wish our new CMO Pia Baumann a warm welcome to the team. Pia is a cancer specialist with solid experience in global drug development, which will be very valuable in the continued clinical development of fostrox. We are glad to note the strong interest in fostrox and that the measures taken have yielded results in patient recruitment for the soon-to-be-completed phase 1b part of the study. Our work to ensure that fostrox can become an effective drug against liver cancer continues unabated. We hope and believe that it will lead to a treatment that makes a real difference for the patients and for the care and thus also for our shareholders. I look forward to keeping you informed of Medivir's continued development. Jens Lindberg Chief Executive Officer For further information, please contact Magnus Christensen, CFO Phone: +46 (0)8 5468 3100 E-mail: magnus.christensen@medivir.com This report has not been subject to auditors' review. The information was submitted for publication at 08.30 CET on February 15, 2023. The following files are available for download: View original content: SOURCE Medivir Company Codes: Stockholm:MVIRB, Bloomberg:MVIRB@SS, ISIN:SE0000273294, RICS:MVIRB.ST

临床1期高管变更财报

100 项与 MET-X 相关的药物交易

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