bleomycin

ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.

Extracranial and nonvaginal EMGCTs are a heterogeneous group of tumors due to their varied onset ages, location, and clinical presentation. An all-around clinical evaluation is crucial for selecting appropriate treatment. Most patients achieve a good prognosis after surgical resection and chemotherapy. Patients with these rare diseases may benefit from individualized treatment and timely referral to experienced medical centers.

P3, N=500, Completed, Fondazione Italiana Linfomi - ETS | Active, not recruiting --> Completed

In addition, the GAA-treated group showed a significant decrement in the levels of TGF-β, Smad2&3, P38 MAPK, TNF-α, IL1β, and MDA compared to BLM induced lung fibrosis group. GAA has a protective impact on lung fibrosis induced by BLM via downregulation of TGF-β and upregulation of CAV1 level and GCL expression which may play a critical role in the improvement of the pathogenesis of lung fibrosis induced via BLM.

Further in vitro studies showed that ILA could improve the aging of 3T3-L1 mouse embryonic fibroblasts induced by bleomycin, reduce the protein expression of the aging marker P21, alleviate inflammation, and enhance the ability of preadipocytes to mature. Therefore, APS had the efficacy of protecting naturally aging mice, and its action may be related to the increase in the intestinal microbiota metabolite ILA. This study suggested that TCM may serve as an important entry point for explaining the mechanism of action of TCM by regulating intestinal microbiota and their functional metabolites.

Alpinia officinarum Rhizomes extract appears to protect against bleomycin-induced PF, possibly due to its antioxidant, anti-inflammatory, and antifibrotic properties.

Four chemotherapy agents were chosen as priority hits for mechanistic follow-up due to their ability to enhance T-cell-mediated cytotoxicity at multiple doses and multiple time points: paclitaxel, bleomycin sulfate, ispinesib, and etoposide. Based on the ability to increase tumor cell susceptibility to T-cell-mediated cytotoxicity while minimizing T-cell toxicity, bleomycin was identified as the most promising lead candidate. Overall, the results of these studies provide mechanistic insight into potential new chemotherapy partners to enhance anti-PD-1 efficacy in TNBC patients.

Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy.

These findings suggest that a one-two punch strategy of pro-senescence therapy induced by chemotherapy treatment followed by senolytic therapy represents a new paradigm for the pharmacological treatment of VS.

The experimental results showed that loss of PTPN21 exacerbated lung fibrosis by increasing cell numbers in bronchoalveolar lavage fluid, lung hydroxyproline content, and extracellular matrix protein expression of fibronectin and α-smooth muscle actin (α-SMA) in bleomycin-challenged mouse lungs...However, treatment of MRC-5 and PHLF with the supernatant from PTPN21-overexpressing A549 cells only slightly reduced the expression of fibronectin, collagen 1 in MRC-5 cells, but did not change the expression of α-SMA. In summary, this study revealed that the loss of PTPN21 in epithelial cells disrupted mitochondrial metabolic homeostasis, leading to epithelial cell inactivation and increased the deposition of extracellular matrix proteins in fibroblasts, thereby exacerbating experimental pulmonary fibrosis.

P=N/A, N=70, Not yet recruiting, The Fourth Affiliated Hospital of Zhejiang University School of Medicine

Taken together, this study underscores the environmental and health risks associated with the accumulation of cytostatic drugs like BLM and highlights the therapeutic potential of natural compounds such as peimine. Our results contribute to the development of novel strategies for the prevention and treatment of pulmonary fibrosis and call for better management practices to mitigate the environmental impact of cytostatic drugs.

High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

In the bleomycin-induced lung fibrosis mouse model, c1 decreased fibrous protein production and deposition in the lung tissues; at a 30 mg/kg dose, it reduced the levels of α-SMA and Col-1 to 48.12 and 56.37% of the BLM group, respectively. The pharmacokinetics tests showed c1 relative distribution rate in lung tissue (at 1 h, 18.86%; at 2 h, 12.80%) is much higher than that of GA (at 1 h, 2.8%; at 2 h, 1.9%). These results show compound c1 is likely to be a candidate for acute lung injury and pulmonary fibrosis.

This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

P=N/A, N=70, Not yet recruiting, Assiut University

Using a bleomycin and COVID-19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not, by themselves, drivers of fibrosis in the lung.

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

Our findings suggest that glabridin and Dex may exert anti-fibrotic effects by suppressing oxidative stress and inhibiting the inflammatory response, and that glabridin may improve pulmonary function through activation of BKCa channels. Both glabridin and Dex may therefore be of therapeutic use in pulmonary fibrosis.

Our study demonstrates that IAA alleviates PF through multiple pathways, highlighting its potential as a therapeutic agent.

P=N/A, N=30, Recruiting, Istituto Ortopedico Rizzoli

P3, N=348, Active, not recruiting, St. Olavs Hospital | Trial completion date: Dec 2035 --> May 2032 | Trial primary completion date: Dec 2035 --> May 2027 | Recruiting --> Active, not recruiting

Our findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.

P3, N=300, Recruiting, State Budgetary Healthcare Institution, National Medical Surgical Center N.A. N.I. Pirogov, Ministry of Health of Russia | Trial primary completion date: Dec 2023 --> Dec 2026

Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out...Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria... According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

Postoperatively, a five-cycle chemotherapy regimen comprising bleomycin, etoposide, and cisplatin was administered. During postoperative follow-up, the patient's general condition was noted to be good, with the newborn and pregnant women ultimately achieving good outcomes. We reviewed the relevant literature to increase clinical doctors' understanding of ovarian malignancy during pregnancy, guide treatment selection, and facilitate early intervention for associated diseases.

Mice were randomized into normal, model, pirfenidone(50 mg·kg~(-1)), low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Qingqiao, and low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Laoqiao groups. In conclusion, both Qingqiao and Laoqiao were effective in ameliorating bleomycin-induced pulmonary fibrosis in mice. Laoqiao was superior to Qingqiao in reducing collagen deposition, which might be attributed to the higher content of hydroxytyrosol, caffeic acid, phillygenin, and(-)-lariciresinol in Laoqiao than in Qingqiao.

Glod4 depletion in N2a-APPswe cells upregulated AβPP, and downregulated autophagy-related Atg5, p62, and Lc3 genes. These findings suggest that GLOD4 interacts with AβPP and the autophagy pathway, and that disruption of these interactions leads to Aβ accumulation and cognitive/neurosensory deficits.

This study revealed that EQ regulated pulmonary fibrosis and cellular immunity by inhibiting HSP90, appearing to act through the TGF-β/Smad2/3 pathway. These findings suggest that EQ holds potential as a therapeutic agent for treating RA-ILD.

CGA is a promising multi-target therapeutic agent for IPF, which is supported by its efficacy in reducing fibrosis through the modulation of key pathways. This evidence provides a basis to further investigate CGA as an IPF potential treatment.

Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

We used CODA-PGX to screen a diverse collection of clinical stage drugs and report dozens of novel LoF genetically targeted opportunities; many validated in xenografts and by real-world evidence. Notable examples include treating STAG2-mutant tumors with Carboplatin, SMARCB1-mutant tumors with Oxaliplatin, and TP53BP1-mutant tumors with Etoposide or Bleomycin.

P1/2, N=82, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

By combining multiple ML algorithms, we developed a novel prognostic model with excellent performance in PAAD cohorts. ML also proved to be powerful for identifying biomarkers and potential targets for improved PAAD patient stratification and immunotherapy.

Despite being a rare event, CHL may first develop in extranodal sites, such as the palatine tonsil. In this context, the role of the dentist is pivotal for early diagnosis of the disease. Investigations into the development of primary tonsillar CHL in the oropharynx are needed because the disease has a different clinical course than nodal lesions.

To address MHC-I downregulation, we conducted a high-throughput flow cytometry screen, identifying bleomycin (BLM) as a potent inducer of cell surface MHC-I expression...Importantly, low-dose BLM treatment in mouse models amplified the anti-tumor effect of immunotherapy without detectable pulmonary toxicity. In summary, our findings repurpose BLM as a potential inducer of MHC-I, enhancing its expression to improve the efficacy of T-cell-based immunotherapy.

These findings collectively highlight EF24 as a new and effective therapeutic agent against IPF by inhibiting senescence in AECs.

P2, N=46, Active, not recruiting, Academic and Community Cancer Research United | Trial completion date: May 2024 --> Sep 2024

Ultimately, it was demonstrated that SASP-mediated PD-L1 up-regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON-induced senescence on PD-L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin-related compounds and the clinical transformation of BON.

In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

P=N/A, N=30, Not yet recruiting, Assiut University

Our study produced a reliable prognostic prediction model using only 5 CRs. We found that AURKB promotes immunogenicity and immune infiltration. This research provides crucial support for the development of prognostic biomarkers and treatment strategies for ccRCC.