P=N/A, N=1664, Not yet recruiting, Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology; Tongji Hospital, Tongji Medical College ,Huazhong University o

Treatment with prednisolone and mycophenolate mofetil was initiated, resulting in subsequent clinical improvement. In conclusion, this case of anti-MDA5 positive CADM underscores the diverse range of clinical and radiological findings and the diagnostic challenges they pose. It highlights the importance of anti-MDA5 antibodies as a valuable diagnostic and prognostic tool, given their association with an elevated risk of developing interstitial lung disease (ILD), which may follow a rapidly progressive course and can be further complicated by pneumomediastinum.

P2, N=300, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Feb 2024 --> Apr 2025

Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8+ T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence.

P4, N=350, Not yet recruiting, Mayo Clinic | Initiation date: Oct 2024 --> Jan 2025

The combination treatment also enhanced the upregulation of proapoptotic markers such as Bax, Caspase-3, -9, and cytochrome C, while downregulating the expression of the antiapoptotic marker Bcl-2. Therefore, the current discoveries suggest that Ebs could be employed as a drug candidate for reversing MDR in cancer cells by regulating cellular redox homeostasis.

P1/2, N=54, Recruiting, Eyestem Research Pvt. Ltd. | Trial primary completion date: Oct 2024 --> Apr 2025

In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases.

Prednisone was reinitiated at 1 mg/kg, and she was started on mycophenolate mofetil (MMF). Despite this, a rapid response to corticosteroids was observed including reversal of profound transfusion dependence, normalization of hemoglobin, and reversal of biochemical evidence of hepatic inflammation. A shared pathogenesis of autoimmune fibrosis in both the bone marrow and liver is speculative but suggested by the temporal association in this case.

P=N/A, N=72, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P4, N=204, Completed, Chinese PLA General Hospital | Recruiting --> Completed

P3, N=84, Completed, University Medical Center Groningen | Unknown status --> Completed

P4, N=350, Not yet recruiting, Mayo Clinic

P4, N=20, Recruiting, University Hospital, Antwerp | Not yet recruiting --> Recruiting

P4, N=130, Completed, University Hospital, Strasbourg, France | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2024

Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.

Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.

P2, N=40, Completed, Sound Pharmaceuticals, Incorporated | Enrolling by invitation --> Completed | N=80 --> 40

P3, N=254, Completed, Sound Pharmaceuticals, Incorporated | Active, not recruiting --> Completed

The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.

P2, N=60, Not yet recruiting, Medical College of Wisconsin

She was treated with mycophenolate mofetil monotherapy for her skin manifestations...He was started on nintedanib...Given her lack of respiratory symptoms and normal PFTs, she was not initiated on ILD-specific treatment. While anti-MDA5 ILD is certainly associated with RP-ILD, clinicians should maintain awareness that there may be cases of asymptomatic or slowly progressive ILD as well.

P2, N=19, Completed, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Unknown status --> Completed | Trial completion date: Mar 2021 --> Jun 2024 | Trial primary completion date: Mar 2021 --> Mar 2024

P=N/A, N=12, Recruiting, Peking University People's Hospital

P=N/A, N=34, Recruiting, Peking University People's Hospital

P=N/A, N=100, Recruiting, Renji Hospital, Shanghai Jiao Tong University School of Medicine; Renji Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting

P4, N=20, Not yet recruiting, University Hospital, Antwerp

Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels...Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

P4, N=50, Recruiting, University of California, Davis | Trial completion date: Jan 2023 --> Jan 2025 | Trial primary completion date: Dec 2022 --> Dec 2024

In U251 cells, MPA displayed strong cytotoxic synergy with BCNU and moderate synergy with irinotecan, oxaliplatin, paclitaxel, or temozolomide (TMZ). In U87 cells, MPA displayed strong cytotoxic synergy with all except TMZ, acting primarily through the apoptotic pathway. Our work expands the mechanistic potential of IMPDH inhibition to TERT/telomere regulation and reveals a synthetic lethality between MPA and anti-GBM drugs.

P=N/A, N=64, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting | Trial completion date: Aug 2024 --> Jul 2025 | Trial primary completion date: Aug 2024 --> Jul 2025

P1/2, N=54, Recruiting, Eyestem Research Pvt. Ltd. | Not yet recruiting --> Recruiting

AD analogues derived from compound 9 inhibit IMPDH in vitro and cause cell death by inhibiting IMPDH in cells. These findings nominate these compounds as preclinical candidates for the development of tumor-activated IMPDH inhibitors to treat neuronal cancers.

Higher levels and a preferential nuclear localization of GSTP protein were also observed in HepG2 and Huh-7 hepatocarcinoma cells compared to HepaRG non-cancerous cells, along with increased basal and Ebselen-stimulated levels of free GSH and PSSG...Nrf2 nuclear translocation and β-TrCP expression also increased in HCC cells, whereas the GSTP transfection in HepaRG cells induced Nrf2 transcriptional activation. In conclusion, GSTP expression and subcellular distribution can contribute to the GSH-dependent redox reprogramming of HCC cells directly influencing the Nrf2/Keap1 system.

P4, N=158, Recruiting, Chong Kun Dang Pharmaceutical | Not yet recruiting --> Recruiting

However, the patient reported a severe headache following treatment with oral prednisolone and tacrolimus. Tacrolimus was discontinued, and mycophenolate mofetil was instead administered with a favorable outcome. Mycophenolate mofetil should therefore be considered as an alternative treatment for anti-MDA-5-positive interstitial lung disease in cases where calcineurin inhibitors cannot be used.

P3, N=346, Active, not recruiting, Hospices Civils de Lyon | Recruiting --> Active, not recruiting

Various bile duct imaging findings of immune-related adverse event-sclerosing cholangitis were revealed; transpapillary bile duct biopsy may be useful in the diagnosis of immune-related adverse event-sclerosing cholangitis. Despite the combination of multiple immunosuppressive agents, prognosis of immune-related adverse event-sclerosing cholangitis remains poor. Longer follow-up and larger clinical studies are necessary to establish its treatment strategy.

P1/2, N=54, Not yet recruiting, Eyestem Research Pvt. Ltd.

P1, N=39, Recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Not yet recruiting --> Recruiting

P2, N=40, Not yet recruiting, Sound Pharmaceuticals, Incorporated

P=N/A, N=63, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting