Therefore, this strategy can have significant potential in the prevention of tumor metastases and recurrence. To the best of our understanding, this study represents a pioneering showcase of tumor pyroptosis, induced by glycolytic inhibitors, which can be effectively coordinated with DIP-mediated TAM polarization for immune activation, offering a new paradigm for differentially sustained drug delivery to foster cancer immunotherapy.

P1, N=6, Recruiting, City of Hope Medical Center | Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Jun 2027

Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.

We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2...This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPβ. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention.

This study predicted the therapeutic target of IBD and the molecular mechanism of dipyridamole in treating IBD, providing a new direction for the treatment of IBD and a theoretical basis for further research.

The cytokine and sPD-L1 levels may differ between serum and plasma samples collected from cancer patients treated with immunotherapy, and the results obtained can be influenced by the different characteristics of the tested assays. The standardization of pre-analytical and analytical procedures is therefore needed for the future implementation of these circulating biomarkers in clinical practice.

P2, N=12, Active, not recruiting, Chulalongkorn University

P1, N=6, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Apr 2024

P4, N=460, Recruiting, The First Affiliated Hospital of Guangzhou Medical University; The First Affiliated Hospital of Guangzhou Medical University | Phase classification: P3 --> P4

P1, N=6, Not yet recruiting, City of Hope Medical Center | Trial completion date: Sep 2025 --> Oct 2026 | Initiation date: Jun 2023 --> Jan 2024 | Trial primary completion date: Sep 2025 --> Oct 2026

Furthermore, it has been determined that dipyridamole can effectively suppress the proliferation of MM cells with high-expression levels of PRUNE1 in vitro and in vivo. These findings provide insights into disease-causing mechanisms and new therapeutic targets for MM patients with 1q21+.

In contrast, GTP-induced cell death was suppressed not only by adenosine and dipyridamole, but also by the A1 receptor agonist CCPA, suggesting that GTP-induced cell death is mediated in part by an antagonistic effect on adenosine A1 receptor. Thus, both guanosine and GTP induce apoptosis of breast cancer cells, but via at least partially different mechanisms.

Similarly, chlorogenic acid exhibited a binding energy score (ΔG = - 18.76 ± 4.60 kcal/mol) comparable to those of the two approved ADA inhibitor drugs pentostatin (ΔG = - 14.54 ± 2.25 kcal/mol) and cladribine (ΔG = - 25.52 ± 4.10 kcal/mol) while quercetin was found to have modest binding affinity (ΔG = - 8.85 ± 7.32 kcal/mol). This study provides insights into the possible inhibitory potential of these phenolic compounds against ADA.

We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.

In our large institutional cohort of patients with HCL, a considerable fraction (35%) of patients experienced serious or opportunistic infections. The majority of these were in the 2 months before or after initial treatment. We did not identify any demographic or disease factors associated with infection, although this is limited by the small sample size.

Treatment with the monoclonal antibody to CD52-alemtuzumab (alem) has considerably improved outcomes, yet with transient responses. Bendamustine (benda) showed encouraging results, particularly in alem-refractory patients (pts)...Thirty pts (23.6%) received first line benda 90 mg/m2 on D1 then 2x6 cycles every 28 days (median 3; 1-6), 15 (11.8%) received pentostatin, 11 (8.6%) had a CHOP-like regimen...Prospective trials are needed to define the most effective therapeutic strategy and improve clinical responses to frontline therapy. New approaches using well-tolerated targeted therapies involving growth and survival signals are needed for the majority of patients unable to receive intensive chemotherapy.

Leveraging this knowledge, we develop an integrative pharmacogenomics pipeline to identify compounds similar to dipyridamole at the level of drug structure, cell sensitivity and molecular perturbation...We validate top-ranked compounds, nelfinavir and honokiol, and identify that low expression of the canonical epithelial cell marker, E-cadherin, is associated with statin-compound synergy. Analysis of remaining prioritized hits led to the validation of additional compounds, clotrimazole and vemurafenib. Thus, our computational pharmacogenomic approach identifies actionable compounds with pathway-specific activities.

P2, N=200, Recruiting, National Cancer Institute (NCI) | N=74 --> 200

Using an in silico/crystallography supported design, we identified compound 4 (IC 7.2 nM), characterized by the presence of a decorated aryloxyaryl moiety that replaced the biphenyl scaffold, with potent inhibition and pro-differentiating abilities on AML THP1 cells (EC 74 nM), superior to those of brequinar (EC 249 nM) and boosted when in combination with dipyridamole. Finally, compound 4 has an extremely low cytotoxicity on non-AML cells as well as MEDS433; it has shown a significant antileukemic activity in vivo in a xenograft mouse model of AML.

Initial treatment with propranolol was unsuccessful. After initiation of selumetinib, bleeding stopped and allowed the patient to be discharged from the hospital on dipyridamole as antiplatelet prophylaxis for his mechanical mitral valve. He had no further bleeding episodes through 1 year after hospital discharge.

After admission, she was restarted tacrolimus and steroids at 2 mg/kg for 5 days and then infliximab 10 mg weekly (2 doses)...If there is no improvement within 5 days then second-line agents (extracorporeal photopheresis, IL 2 Receptor antibodies, anti-TNF antibodies, mTOR inhibitors, and MMF) and third-line agents (mesenchymal stem cells, methotrexate, alemtuzumab, pentostatin) are used. Ruxolitinib (JAK inhibitor) is one of the newest therapies used for steroid refractory GVHD. Figure: A. Bile duct injury identified by intraepithelial lymphocytes, cytoplasmic vacuolization, and nuclear disarray (H&E, 200x) B. CK7 immunohistochemical stain showing loss of bile duct and biliary hepatic metaplasia(CK7, 200X)

ACP with high CXCL6 showed remarkable drug sensitivity to Pentostatin and Wortmannin via CellMiner database analysis. Our results deepened the understanding of the molecular immune mechanism in ACP and provided potential biomarkers for the precisely targeted therapy for ACP.

Most patients respond to purine nucleoside analogs (PNA) like cladribine or pentostatin...Chemo-immunotherapy using PNA and rituximab (R), BRAF, MEK, or Bruton Tyrosine Kinase (BTK) inhibitors may be used. Good results were recently published and achieved with moxetumomab pasudotox (Moxe), an anti-CD22 immunoconjugate. In this review, we will present an update on HCL and HCL-V, focusing on pathophysiology and recent therapeutic advances.

ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Dipyridamole also duplicated the biochemical changes and apoptosis in glioma T98G cells. Since dipyridamole has additional biochemical and pharmacological properties, further research centered on the anti-glioma mechanisms of dipyridamole is still needed.

In a first-generation trial using ex vivo rapamycin, polyclonal autologous Th1/Tc1 (RAPA-101) cells were safe and associated with delayed relapse when administered after hematopoietic cell transplantation in high-risk MM patients. Now, we are evaluating temsirolimus for manufacture of second-generation RAPA-201 cells...Bridging chemotherapy during manufacturing (Cycle 1) and host conditioning prior to RAPA-201 infusion consisted of the 14-day PC regimen [pentostatin (4 mg/m 2 IV; days 1, 4, 8, 12; dose adjusted/omitted with renal insufficiency); cyclophosphamide (100-200 mg PO, days 1-5 and days 8-12)]...RAPA-201 therapy represents a new paradigm that utilizes stringent mTOR inhibition to reprogram Th1/Tc1 cells for enhanced metabolic fitness and induction of in vivo T cell clonal expansion, thus providing an alternative to gene-modified targeted T cell therapy. With these promising safety and efficacy results, current RAPA-201 developmental efforts are directed towards completing protocol accrual in parallel with the design and implementation of next-generation clinical trials.

VEN was started with daily ramp-up from 20 mg to 800 mg over 6 days, with TLS prophylaxis (rasburicase and IV hydration)... All 15 patients were refractory or relapsing after chemotherapy (mostly bendamustine and pentostatin), except one... These preliminary results suggest promising activity of RUX plus VEN in T-PLL, and justify the development of a prospective clinical trial of this combination. Our data seem to show that this combination may be especially active for patients with JAK/STAT pathway activating mutations and that disease progression is associated with clonal evolution. Updated results will be presented at the meeting.

P2, N=74, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Oct 2022 --> Oct 2025

Between 2 to 4 months after transplant, higher alemtuzumab levels measured 14 days after transplant correlated with patients having better engraftment, suggesting more lymphodepletion may be needed to reduce graft failure in these two non-myeloablative matched related donor HSCT regimens.

We combined Pentostatin with immune checkpoint inhibitors and observed synergistic anti-cancer activities. Our work identifies Pentostatin as a new class of anticancer immunostimulating drug that activates innate immunity within tumour tissues and synergizes with systemic T-cell therapies.

Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics.

Inhibition of SREBP signaling with dipyridamole enhanced the cytotoxicity of KPT-9274 on LSCs in vivo. Our work demonstrates that altered lipid homeostasis plays a key role in NAMPT inhibitor-induced apoptosis and identifies NAMPT inhibition as a therapeutic strategy for targeting LSCs in AML.

Methods Since 2000, 40 patients have been infused with autologous CD34+ cells engineered with a γ-RV encoding ADA following low dose busulfan...The patient showed poor prednisone response, while morphological complete remission was obtained at the end of induction therapy of the AIEOP-BFM ALL 2017 protocol...Due to the identified risk of leukaemogenesis, patients will continue long-term FU to closely monitor the safety of the product. EMA CHMP confirmed that the risk/benefit balance remains favorable for Strimvelis in its approved indication.

The administration of naringin and pentostatin, inhibitors for adenosine deaminase (ADA), enzyme responsible for cordycepin degradation, did not show a synergistic effect in MPNST cells treated with cordycepin. The p53 protein could ameliorate the effect. In summary, cordycepin is effective to inhibit the growth of MPNST, probably through the pathway of p53/Sp1/tubulin.

The aim of this study was to evaluate the effect of the NSAIDs, naproxen, piroxicam, meloxicam, ibuprofen, sodium diclofenac, acetylsalicylic acid, nimesulide, and ketoprofen on CD73 expression in GBM and mononuclear cells...For analysis of the mechanism of action of MTX, GBM cells were treated with APCP (CD73 inhibitor), dipyridamole (inhibitor of adenosine uptake), ABT-702 (adenosine kinase enzyme inhibitor), or caffeine (P1 adenosine receptor antagonist), before treatment with MTX and AMP, in the presence or not of mononuclear cells. In summary, only MTX increased the expression of CD73 in GBM cells decreasing cells viability by mechanisms independent of the adenosinergic system. Further studies are needed to understand the role of MTX in the GBM microenvironment.

Those released substances and exosomes, along with exogenous HMGB1, promoted cancer cell survival and protected cells from doxorubicin cytotoxicity. The suppressive effect of dipyridamole on cancer cell survival was paralleled by a reduction of HMGB1/receptor for advanced glycation end-products axis, and proliferation- and migration-related β-catenin, Yes-associated protein 1, Runt-related transcription factor 2, and TGF- β1/Smad signals. Therefore, exosomes and exosomal HMGB1 appear to have roles in platelet-driven cancer malignancy and represent targets of antiplatelet drugs in anticancer treatment.

However, the combined usage of dipyridamole significantly enhanced the cytotoxicity of doxorubicin to HCT-8 cells at particular doses. Based on the current findings, dipyridamole likely induces the phosphorylation of CREB to promote the proliferation of cancer cells, but may enhance the cytotoxicity of anti-cancer drugs at particular doses.

P2, N=74, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2025

To explore the translational application of our findings, we tested whether dipyridamole (DP), a clinically approved anti-platelet agent with inhibitory activity against SREBP signaling, can be repurposed to enhance the anti-leukemic effects of KPT-9274. We further uncovered that NAMPT inhibition results in dysregulation of lipid homeostasis and induces a lipogenic response coordinated by SREBPs that protects AML cells against NAD+ depletion. These findings offer insights into drug combination strategies to enhance the efficacy of NAMPT inhibitors and provide the rationale for testing NAMPT inhibitors in the treatment of AML in clinical trials.