A Phase I/II, Open-label Study to Evaluate the Abscopal Response and Safety of Manganese and Standard-of-care Radiotherapy/ SBRT in Subjects With Metastatic Solid Tumors or Lymphoma

Radiotherapy is a regular care for metastatic solid tumors or lymphoma, and it can induce immunogenic death of tumor cells and a stronger immune response. Sometimes, tumor regression would be observed at sites distant to an irradiated field because of the radiotherapy-induced anticancer immune responses, so-called abscopal response. Manganese has been confirmed to activate innate immune and function as anticancer immunoadjuvant in pre-clinical studies. This study is designed to assess the abscopal response and safety of combined therapy of manganese and radiotherapy in patients with metastatic solid tumors or lymphoma.

Start Date06 May 2021

Sponsor / Collaborator

Chinese People's Liberation Army General Hospital

NCT03989336

/ CompletedPhase 2IIT

A Randomized, Single-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Relapsed/Refractory Ovarian Cancer

Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Platinum chemotherapy has been widely adopted as a standard treatment for advanced ovarian cancer, the response rates in patients with relapsed/refractory ovarian cancer is unacceptably low. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This two-arm, phase I/II study is designed to assess the safety and efficacy of combined therapy of anti-PD-1 antibody and chemotherapy with or without Manganese priming.

Start Date23 Dec 2020

Sponsor / Collaborator

Chinese People's Liberation Army General Hospital

NCT04004234

/ Unknown statusPhase 1/2IIT

A Phase I/II, Open-label, Single-center Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Local Advanced/Metastatic Biliary Tract Cancer

Biliary tract cancer (BTC) is a rare heterogeneous collection of malignancies arising within the biliary tract, characterized by innate chemoresistance and abysmal prognosis. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This open-label, phase I/II study is designed to assess the safety and efficacy of Manganese primed combined therapy of anti-PD-1 antibody and gemcitabine/cisplatin chemotherapy.

Start Date01 Mar 2019

Sponsor / Collaborator

Chinese People's Liberation Army General Hospital

100 Clinical Results associated with Manganese Chloride

100 Translational Medicine associated with Manganese Chloride

100 Patents (Medical) associated with Manganese Chloride

331

Literatures (Medical) associated with Manganese Chloride

01 Jan 2025·FEBS Journal

USP15 inhibits hypoxia‐induced IL‐6 signaling by deubiquitinating and stabilizing MeCP2

Article

Author: Zhang, Yu ; Yu, Chen‐Hao ; Huang, Kun ; Liu, Cheng‐Yu ; Zheng, Ling ; Zhang, Zi‐Tong ; Wan, Shi‐Yuan ; Niu, Shu‐Xuan ; Wang, Jiao

Methyl‐CpG binding protein 2 (MeCP2) is an important X‐linked DNA methylation reader and a key heterochromatin organizer. The expression level of MeCP2 is crucial, as indicated by the observation that loss‐of‐function mutations of MECP2 cause Rett syndrome, whereas an extra copy spanning the MECP2 locus results in MECP2 duplication syndrome, both being progressive neurodevelopmental disorders. Our previous study demonstrated that MeCP2 protein expression is rapidly induced by renal ischemia–reperfusion injury (IRI) and protects the kidney from IRI through transcriptionally repressing the interleukin‐6 (IL‐6)/signal transducer and activator of transcription 3 signaling pathway. However, the mechanisms underlying the upregulation of MeCP2 have remained elusive. Here, by using two hypoxia cell models, hypoxia and reoxygenation and cobalt chloride stimulation, we confirmed that the removal of lysine 48‐linked ubiquitination from MeCP2 prevented its proteasome‐dependent degradation under hypoxic conditions. Through unbiased screening based on a deubiquitinating enzymes library, we identified ubiquitin‐specific protease 15 (USP15) as a stabilizer of MeCP2. Further studies revealed that USP15 could attenuate hypoxia‐induced MeCP2 degradation by cleaving lysine 48‐linked ubiquitin chains from MeCP2, primarily targeting its C‐terminal domain. Consistently, USP15 inhibited hypoxia‐induced signal transducer and activator of transcription 3 activation, resulting in reduced transcription of IL‐6 downstream genes. In summary, our study reveals an important role for USP15 in the maintenance of MeCP2 stability and the regulation of IL‐6 signaling.

01 Jan 2025·JOURNAL OF CELLULAR BIOCHEMISTRY

Role of Sodium‐Dependent Vitamin C Transporter‐2 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells

Article

Author: Robinson, Bridget A. ; Praditi, Citra ; Vissers, Margreet C. M. ; Dachs, Gabi U. ; Phillips, Elisabeth ; Burgess, Eleanor R. ; Wiggins, George A. R.

ABSTRACT:

The most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro‐tumour transcription factor, hypoxia‐inducible factor (HIF), is regulated via HIF‐hydroxylases that require ascorbate as cofactor. Decreased HIF‐hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium‐dependent vitamin C transporter‐2 (SVCT2). We hypothesize that glioblastoma cells rely on SVCT2 for ascorbate accumulation, and that knockout of this transporter would disrupt the regulation of the hypoxic pathway by ascorbate. Ascorbate uptake was measured in glioblastoma cell lines (U87MG, U251MG, T98G) by high‐performance liquid chromatography. CRISPR/Cas9 was used to knockout SVCT2. Cells were treated with cobalt chloride, desferrioxamine or 5% oxygen, with/without ascorbate, and key hypoxic pathway proteins were measured using Western blot analysis. Ascorbate uptake was cell line dependent, ranging from 1.7 to 11.0 nmol/106 cells. SVCT2‐knockout cells accumulated 90%–95% less intracellular ascorbate than parental cells. The hypoxic pathway was induced by all three stimuli, and ascorbate reduced this induction. In the SVCT2‐knockout cells, ascorbate had limited effect on the hypoxic pathway. This study verifies that intracellular ascorbate is required to suppress the hypoxic pathway. As patient survival is related to an activated hypoxic pathway, increasing intra‐tumoral ascorbate may be of clinical interest.

01 Dec 2024·Applied microbiology and biotechnology

Transcriptomic profiling of adding cobalt chloride to improve dendrobine-type total alkaloid production

Article

Author: Qian, Xu ; Chen, Jishuang ; Qin, Yitong ; Sarasiya, Surendra

Trichoderma longibrachiatum UN32 is known for its efficient production of dendrobine-type total alkaloids (DTTAs). This study aimed to determine the optimal medium composition for the UN32 strain using response surface methodology. Key factors, including glucose, beef extract, and CoCl₂, were selected through the Plackett-Burman design. Subsequently, a factorial optimization approach was employed using the steepest ascent design, and 17 trial sets were completed via the Box-Behnken design. The optimal medium composition was found to consist of 29.4 g/L of glucose, 17.3 g/L of beef extract, and 0.28 mmol/L of CoCl₂. This optimized medium resulted in an impressive 80.8% increase in mycelial dry weight (reaching 12.303 g/L) and a substantial 76.4% boost in DTTA production (reaching 541.63 ± 46.95 μg). Furthermore, the fermentation process was scaled up to a 5-L bioreactor, leading to a DTTA production approximately 1.95 times than the control. Transcriptome analysis of strain UN32 in response to CoCl₂ supplementation revealed significant changes in the expression of critical genes associated with the TCA cycle and L-valine, L-leucine, and L-isoleucine biosynthesis changed. These alterations resulted in a heightened influx of acetyl-CoA into DTTA production. Additionally, the expression of genes related to antioxidant enzymes was modified to maintain homeostasis of reactive oxygen species (ROS). A potential mechanism for the accumulation of DTTAs based on ROS as a signal transduction was proposed. These findings provide valuable insights into the regulatory mechanisms of DTTA biosynthesis, potentially offering a method to enhance the production of secondary metabolites in the UN32 strain. KEY POINTS: • After the RSM optimization, there is a substantial increase of 80.8% in biomass production and a significant 76.4% rise in DTTA production. • Transcriptome analysis revealed that the inclusion of CoCl₂ supplements resulted in an enhanced influx of acetyl-CoA. • Proposed a mechanism for the accumulation of DTTAs for the role of ROS as a signal transduction pathway.

News (Medical) associated with Manganese Chloride

23 Dec 2024

·www.accesswire.com

Ascelia Pharma Patent Granted in China for Second Generation Orviglance

MALMÖ, SWEDEN / ACCESSWIRE / December 23, 2024 / Ascelia Pharma (STO:ACE) Ascelia Pharma AB (publ) (ticker: ACE), a biotech focused on improving the life of people living with rare cancer conditions, today announced that the Chinese patent authorities have granted patent protection for the second-generation Orviglance®The new patent covers the effervescent tablet formulation of Orviglance. This formulation makes it even easier for patients and health care professionals to use the product. This patent protection until 2040 in China further strengthens the value proposition of the Orviglance franchise.ContactsMagnus Corfitzen, CEOEmail: [email protected]Tel: +46 735 179 118Julie Waras Brogren, Deputy CEO (Finance, Investor Relations & Commercial)Email: [email protected]Tel: +46 735 179 116This information was submitted for publication, through the agency of the contact persons set out above.About usAscelia Pharma is a biotech company focused on orphan oncology treatments. We develop and commercialize novel drugs that address unmet medical needs and have a clear development and market pathway. The company has two drug candidates - Orviglance and Oncoral - in clinical development. Ascelia Pharma has global headquarters in Malmö, Sweden, and is listed on Nasdaq Stockholm (ticker: ACE). For more information, please visit http://www.ascelia.com.About OrviglanceOrviglance (manganese chloride tetrahydrate) is a novel oral contrast agent for MR-imaging developed to improve the detection and visualization of focal liver lesions (including liver metastases and primary tumors) in patients with reduced kidney function. These patients are at risk of serious side effects from the currently available class of gadolinium-based contrast agents. Orviglance, has been granted an Orphan Drug Designation by the US Food and Drug Administration (FDA). A clinical program of nine studies, including the pivotal global Phase 3 study SPARKLE, has successfully been completed with strong and consistent efficacy and safety results.AttachmentsAscelia Pharma Patent Granted in China for Second Generation OrviglanceSOURCE: Ascelia PharmaRelated Documents:

Phase 3Orphan Drug

17 Dec 2024

·www.accesswire.com

Ascelia Pharma Announces Acceptance of SPARKLE Phase 3 Data for Presentation at the Society of Abdominal Radiology Congress 2025

MALMO, SWEDEN / ACCESSWIRE / December 17, 2024 / Ascelia Pharma (STO:ACE), a biotech focused on improving the life of people living with rare cancer conditions, today announced that two scientific abstracts with clinical data from the SPARKLE Phase 3 study with Orviglance have been accepted as an oral presentation and a scientific poster at the Society of Abdominal Radiology Congress, taking place from 16-21 February 2025 in Tucson, AZ, US.The two abstracts highlight the positive outcomes of the SPARKLE Phase 3 study. In the study Orviglance was shown to enhance the detection of suspected or known liver lesions, including small-sized lesions, and consistently shows positive results in visualizing lesions in both patients with hepatocellular carcinoma (HCC, primary liver cancer) and those with liver metastases. The study includes patients with severe renal impairment who currently lack an alternative to gadolinium-based contrast MRI.The abstract "Improved detection of focal liver lesions with manganese-based contrast agent in patients with severe kidney impairment: evidence from the SPARKLE study" was accepted as an oral presentation and "Hepatocellular carcinoma (HCC) and hepatic metastases: visualization with manganese-based contrast agent enhanced liver MRI in patients with severe kidney disease, evidence from the SPARKLE study" is to be presented in the abstracts section."The acceptance of these abstracts by the Society of Abdominal Radiology Congress is a key achievement. This prestigious event is renowned for being an important gathering for experts and professionals in the field of abdominal radiology, offering unparalleled opportunities for learning, networking, and showcasing groundbreaking research" says Andreas Norlin, CSO Ascelia Pharma.The oral presentation abstract will be held on Sunday February 16, 2025, from 10:43 AM and will be part of the Clinical Practice Improvement session.ContactsMagnus Corfitzen, CEOEmail: [email protected]Tel: +46 735 179 118Julie Waras Brogren, Deputy CEO (Finance, Investor Relations & Commercial)Email: [email protected]Tel: +46 735 179 116This information was submitted for publication, through the agency of the contact persons set out above.About usAscelia Pharma is a biotech company focused on orphan oncology treatments. We develop and commercialize novel drugs that address unmet medical needs and have a clear development and market pathway. The company has two drug candidates - Orviglance and Oncoral - in clinical development. Ascelia Pharma has global headquarters in Malmö, Sweden, and is listed on Nasdaq Stockholm (ticker: ACE). For more information, please visit http://www.ascelia.com.About OrviglanceOrviglance (manganese chloride tetrahydrate) is a novel oral contrast agent for MR-imaging developed to improve the detection and visualization of focal liver lesions (including liver metastases and primary tumors) in patients with reduced kidney function. These patients are at risk of serious side effects from the currently available class of gadolinium-based contrast agents. Orviglance, has been granted an Orphan Drug Designation by the US Food and Drug Administration (FDA). A clinical program of nine studies, including the pivotal global Phase 3 study SPARKLE, has successfully been completed with strong and consistent efficacy and safety results.AttachmentsAscelia Pharma Announces Acceptance of SPARKLE Phase 3 Data for Presentation at the Society of Abdominal Radiology Congress 2025SOURCE: Ascelia Pharma

Phase 3Orphan Drug

02 Dec 2024

·www.accesswire.com

Ascelia Pharma Presents Orviglance SPARKLE Study Primary Results as Cutting-Edge Research at the 2024 RSNA Annual Meeting

MALMÖ, SE / ACCESSWIRE / December 2, 2024 / Ascelia Pharma (STO:ACE) Ascelia Pharma AB (publ) (ticker: ACE) today presents the primary results from the Orviglance® phase 3 SPARKLE Study as an oral presentation at the world's largest radiology conference, RSNA, in Chicago.As communicated earlier, in the successful SPARKLE study, Orviglance significantly improved the visualization of focal liver lesions compared to unenhanced MRI in patients with suspected or known liver lesions and severe kidney impairment.The results were accepted as an oral presentation at the 2024 annual conference of the Radiological Society of North America, the world's largest radiology conference. The presentation was accepted in the Cutting-Edge Research category and will be presented today by Dr. Alvin Silva, SPARKLE Principal Investigator and Professor of Radiology, Mayo Clinic, Phoenix, United States.Title of presentation: SPARKLE: A Multicenter, Open-label Study to Evaluate the Safety and Diagnostic Efficacy of ACE-MBCA in Patients with Known or Suspected Focal Liver Lesions and Severe Renal ImpairmentTiming of presentation: 2 Dec, 13:30-14:00 CDT, local time ChicagoContactsMagnus Corfitzen, CEOEmail: [email protected]Tel: +46 735 179 118Julie Waras Brogren, Deputy CEO (Finance, Investor Relations & Commercial)Email: [email protected]Tel: +46 735 179 116This information was submitted for publication, through the agency of the contact persons set out above.About usAscelia Pharma is a biotech company focused on orphan oncology treatments. We develop and commercialize novel drugs that address unmet medical needs and have a clear development and market pathway. The company has two drug candidates - Orviglance and Oncoral - in clinical development. Ascelia Pharma has global headquarters in Malmö, Sweden, and is listed on Nasdaq Stockholm (ticker: ACE). For more information, please visit http://www.ascelia.com.About OrviglanceOrviglance (manganese chloride tetrahydrate) is a novel oral contrast agent for MR-imaging developed to improve the detection and visualization of focal liver lesions (including liver metastases and primary tumors) in patients with reduced kidney function. These patients are at risk of serious side effects from the currently available class of gadolinium-based contrast agents. Orviglance, has been granted an Orphan Drug Designation by the US Food and Drug Administration (FDA). A clinical program of nine studies, including the pivotal global Phase 3 study SPARKLE, has successfully been completed with strong and consistent efficacy and safety results.AttachmentsAscelia Pharma Presents Orviglance SPARKLE Study Primary Results as Cutting-Edge Research at the 2024 RSNA Annual MeetingSOURCE: Ascelia Pharma

Clinical ResultPhase 3Orphan Drug

100 Deals associated with Manganese Chloride

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KEGG	Wiki	ATC	Drug Bank
D04852	-	-	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Contrast agents	JP	Meiji Seika Pharma Co., Ltd.	20 Apr 2006
Nutrition Disorders	US	Hospira, Inc.	26 Jun 1986

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 2	CN	Chinese People's Liberation Army General Hospital	06 May 2021
Metastatic Solid Tumor	Phase 2	CN	Chinese People's Liberation Army General Hospital	06 May 2021
Recurrent ovarian cancer	Phase 2	CN	Chinese People's Liberation Army General Hospital	23 Dec 2020
Advanced Bile Duct Carcinoma	Phase 2	CN	Chinese People's Liberation Army General Hospital	01 Mar 2019
Locally Advanced Pancreatic Adenocarcinoma	Phase 2	CN	Chinese People's Liberation Army General Hospital	01 Mar 2019

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03989336 (ASCO 12020 \| ASCO 22020) Manual	Phase 2	Ovarian Cancer Last line	27	nab-paclitaxel+ cisplatin+MnCl2+Sintilimab	ycfrofomnw(qqtucuxaue) = The most common AEs are hematological toxicity (87%), nausea (56%) and vomiting (47%) in both two cohorts. knjqxhhzgj (goqzzabzsu )	Positive	25 May 2020
				cisplatin+nab-paclitaxel+Sintilimab

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