The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.

Consequently, we show that bestatin, a clinically advanced aminopeptidase inhibitor, binds to GPAA1 and blocks GPI attachment, resulting in reduced CD24 cell surface expression, increased macrophage-mediated phagocytosis, and suppressed growth of ovarian tumors. Our study highlights the potential of targeting GPAA1 as an immunotherapeutic approach for CD24+ ovarian cancers.

Bestatin treatment reduced proliferation, migration and colony formation of glioma cells in a CD13-dependent manner while apoptosis was increased. In summary, CD13 has an impact on glioma patient survival and is important for the main function of specific glioma cells.

In conclusion, ECs express a catalytically inactive form of CD13 characterized by an accessible conformation that can be selectively targeted by G4-protein conjugates. This form of CD13 may represent a specific target receptor for ligand-directed targeted delivery of therapeutics to tumors.

The combination of PD-1 antibody and DBDx could achieve enhanced therapeutic antitumor efficacy than anti-PD-1 monotherapy, suggesting potential for using the triple-drug combination DBDx in cancer immunotherapy.

The glycolysis inhibitor 2-deoxy-D-glucose enhanced the antiproliferative effect of ubenimex and CDDP...Moreover, ubenimex inhibited the production of lactic acid and adenosine triphosphate (ATP), as well as the expression of key proteins involved in glycolysis, which was similar to the effects caused by the Hh inhibitor cyclopamine...Ubenimex inhibits glycolysis by targeting the CD13/Hh pathway, thus playing an anti-tumor role together with CDDP. This study demonstrated the adjuvant effect of ubenimex from the perspective of Hh signal-dependent glycolysis regulation.

Our results indicate that Taz inhibition of EZH2 leads to downregulation of β-catenin signaling and eventually decreased expression of CD13 and EpCAM, which are characteristic for CSCs. The present study suggests that Taz could be a promising treatment for HCC including HBV-induced HCC that might be used in combination with radio/chemotherapy to target CSCs and prevent tumor relapse.

In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy.

Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.

In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

A strong synergy of CHR2863 with the statins simvastatin, fluvastatin, lovastatin, and pravastatin was demonstrated in U937 cells and two CHR2863-resistant sublines...This synergistic activity was: (i) specific for APis (e.g., CHR2863 and Bestatin), rather than for other cytotoxic agents; and (ii) corroborated by enhanced induction of apoptosis and cell cycle arrest which increased the sub-G1 fraction. Consistently, statin potentiation of CHR2863 activity was abrogated by co-administration of mevalonate and/or farnesyl pyrophosphate, suggesting the involvement of protein prenylation; this was experimentally confirmed by impaired Rheb prenylation by simvastatin. These novel findings suggest that the combined inhibitory effect of impaired Rheb prenylation and CHR2863-dependent mTOR inhibition instigates a potent synergistic inhibition of statins and APis on human AML cells.

Elevated expression of ANPEP/CD13 indicate shorter survival of EAC patients and a more invasive phenotype of cancer cells in vitro. Validation in a larger sample group is required to better understand the clinical significance of ANPEP/CD13 and other candidate genes.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

Patients in the study group received laparoscopic complete mesocolic resection combined with ubenimex orally...After treatment, the levels of immune molecules in the study group were remarkably higher than those in the control group (p<0.05), while the levels of tumor markers were much lower than those in the latter group (p=0.000). Laparoscopic complete mesocolic excision combined with immunotherapy exhibits a superior therapeutic effect to traditional open surgery in elderly patients with colon cancer, and is worthy of clinical promotion.

Our study demonstrates that CDK12/13 activity represents an exploitable vulnerability in MYC-high Group 3 MB and may pave the ground for new therapeutic approaches for this high-risk brain tumor.

Dominant-negative CDK13 mutations cause oncogenic deficiencies in RNA surveillance.

CDK12 and CDK13 represent valuable therapeutic targets for HGSOC. We uncovered a wide spectrum of CDK12/13 targets as potential therapeutic vulnerabilities for HGSOC. Moreover, our study indicates that CDK12/13 inhibition enhances the efficacy of approved drugs that are already in use for HGSOC or other human cancers.

Furthermore, CCNO promoted tumor cell growth and cetuximab resistance in vivo, and a CDK13 inhibitor effectively inhibited the oncological effect of CCNO. The current study suggests that CCNO may be a driver in the development of LUAD and that its function is related to CDK13 interaction that promotes proliferation signaling activation.

In real-world practice, CD13/CD33 expression can predict the risk of MRD in patients without TKI experience, but has no adverse effect on the prognosis of adult B-ALL patients. Incorporating CD13/CD33 into the standard antibody panels of B-ALL diagnosis and MRD measurements can help predict relapse risk and decisions on therapy options.

These findings clarify the pro-tumorigenic role of CDK13 by direct phosphorylation of translation initiation factors and enhancing protein synthesis. Therefore, therapeutic targeting of CDK13 alone or in combination with rapamycin may pave a new way for cancer treatment.

Additionally, we disclose five novel CDK12 inhibitors. These results may accelerate the discovery of novel chemical-class drugs for cancer treatment.

Materials The mononuclear cells of bone marrow aspirate were obtained from an adult man with ALL after he experienced relapse following induction therapy including imatinib mesylate...Furthermore, the cells were positive for CD13 and CD33 in addition to CD19, CD22 and CD79a antigens. Conclusion This unique cell line is expected to be a valuable tool for understanding the pathogenesis of Ph-positive ALL.

In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN)...Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro.

Relatively higher &lsqb;Bi]Bi-DOTAGA-cKNGRE accumulation of the HT1080 neoplasms (%ID/g: 0.80 ± 0.16) compared with the other organs at 90 min time point yields better tumour-to-background ratios. Therefore, the therapeutic application of APN/CD13-affine &lsqb;Bi]Bi-DOTAGA- cKNGRE seems to be promising in receptor-positive fibrosarcoma treatment.

Overall, our data demonstrate that hsa_circ_0000119 facilitated ovarian cancer development through increasing CDH13 expression via promoting DNMT1 expression by sponging miR-142-5p. Our data demonstrate the potential role of hsa_circ_0000119 in the treatment of ovarian cancer.

Unexpectedly, although ZSQ836 triggered genomic instability in malignant cells, it counterintuitively impaired lymphocytic infiltration in neoplastic lesions by interfering with T cell proliferation and activation. These findings highlight the Janus-faced effects of dual CDK12/CDK13 inhibitors by simultaneously suppressing tumor and immune cells, offering valuable insights into the future direction of drug discovery to pharmacologically target CDK12.

Further, 7f markedly inhibited proliferation of multiple TNBC cell lines including MFM223, with an IC value of 47 nM. Importantly, 7f displayed a significantly improved antiproliferative activity compared to the structurally similar inhibitor 4, suggesting the potential advantage of a CDK12/13 degrader for TNBC targeted therapy.

The addition of potent MMP inhibitors (batimastat, marimastat, ONO4817) and other protease inhibitors (such as aprotinin, Pefabloc SC and bestatin) to the brain endothelial cells, in the presence of various melanoma lines, showed no reduction in the melanoma mediated barrier disruption. The inhibitors batimastat, Pefabloc SC, antipain and bestatin alone decreased the barrier strength. These results suggest that although some MMPs and proteases are released by melanoma cells, there is no direct evidence that they are substantially involved in the initial melanoma-mediated disruption of the brain endothelium.

Furthermore, downregulating the expression of Nav1.6 improve the susceptibility of FTC cells to ubenimex in vitro. These results suggest Nav1.6 accelerates FTC progression through JAK/STAT signaling and may be a potential target for FTC therapy.

After surgery, the research group was treated with intravesical chemotherapy using gemcitabine combined with ubenimex, while the control group was given 40 mg pirarubicin by intravesical instillation. For NMIBC patients receiving bladder-preserving surgery, intravesical gemcitabine combined with immunotherapy can reduce the recurrence rate, relieve lower urinary tract symptoms, increase the tolerance of patients to intravesical chemotherapy and significantly improve the function of T lymphocytes, without obvious increase in adverse drug reactions. Therefore, it is safe and effective, and has certain clinical value.

In addition, UBE combined with PEM therapy was associated with increased SOCS1 expression in patients' serum and knocking down SOCS1 reversed the antitumor effects of UBE and PEM. Overall, combination therapy with UBE and PEM could inhibit the JAK2-STAT3 signaling pathway by upregulating SOCS1 expression to hinder the progression of lung adenocarcinoma cells.

In the in vivo study, the selected APN inhibitors, especially D12, exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies.

In vivo, a STAT3 inhibitor remarkably increased CD8 as well as CD8IFN-γ T cells in the spleen and lymph nodes. Taken together, we substantiated that APN deficiency directly maintains the activation of CD8 T cells to inhibit rhabdomyosarcoma growth by suppressing STAT3 activation, indicating a promising APN-based therapy for the treatment of rhabdomyosarcoma.

Combination of DFP-14323 and low-dose afatinib has shown comparable potential as a first-line treatment for EGFR mutation positive NSCLC with feasible efficacy and good safety profile. We are planning a phase III study to evaluate this combination therapy as compared with other EGFR-TKIs.

We evaluated PDOs sensitivity to carboplatin, PARPi olaparib, CDK12/CDK13i SR-4835, and the combination of olaparib with SR-4835. PDOs profiling may predict treatment responses in patients with PDAC and provide a rationale for prioritizing therapeutic regimens. Furthermore, a synergistic therapeutic effect between olaparib and SR-4835 seems to be present, which, if confirmed and tolerated, could extend the opportunity of targeted therapy to a greater group of patients, by extending eligibility for PARPi irrespective of BRCA germline mutation status.

CD13 is a helpful immunohistochemical marker for the differential diagnosis of meningiomas and their mimics, achieving in combination with epithelial membrane antigen maximal sensitivity (100%) and showing statistically relevant difference of expression in comparison with both schwannomas (p < 0.0001) and solitary fibrous tumor/hemangiopericytomas (p < 0.0001). Furthermore, loss of CD13 expression could be related to outcome as it is associated with worrisome histological findings, mainly in the setting of anaplastic meningiomas.

CD33 and CD13 are prognostic risk factors in patients with MM.

Therefore, we suggest that inhibition of CDK13 and HMGA2 simultaneously could be an effective strategy for high HMGA2 expression GC. To detect the expression of both genes simultaneously and individually could be of benefit to predict prognosis for GC.