CXCR4 overexpression

This novel cancer/stroma/immune triple treatment holds great promise for the treatment of one of the most lethal cancers. Further studies are needed to evaluate the translational potential of this approach.

Furthermore, we found that the inhibition of CXCR4 allowed bortezomib to sensitize CCA to anti-PD1 treatment, with a significant reduction of tumor burden and long-term overall survival. This novel cancer/stroma/immune triple treatment holds great promise for the treatment of CCA.

However, only CD33.CAR-CIKs co-expressing CXCR4wt but not CXCR4mut exerted a more sustained in vivo antileukemic activity and extended animal survival, suggesting a non-canonical role for CXCR4 in modulating CAR-CIK functions independent of BM homing. Taken together, these data suggest that arming CAR-CIKs with CXCR4 may represent a promising strategy for increasing their therapeutic potential for AML.

Blockade of the receptors, either individually or in combination, promoted cell death and led to an abrogation of MIF-driven migration responses in murine and human CLL cells, suggesting that joint activation of both receptors is crucial for CLL cell survival and mobility. These findings indicate that the MIF/CXCR4/CD74 axis represents a novel therapeutic target in CLL.

Our results demonstrate that CXCR4 can serve as a new immunohistochemical diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multicenter, large sample size, and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.

Next, to better mimic the BM microenvironment features, we employed the supernatant of MSCs derived from healthy donors (HDs) or AML patients as a chemotactic stimulus and showed that both CXCR4-overexpressing CD33.CAR-CIK cells demonstrated increased chemotaxis toward HD- and AML-derived MSC supernatants compared to control (n = 14), which was abrogated by CXCR4 antagonist plerixafor...Moreover, CD33.CAR-CIK co-expressing CXCR4WT exerted a superior control of AML progression, with the median survival time increased from 57.5, 77.5, and 87.5 days in the untreated, CD33.CAR+-CIK and CD33.CAR+-CXCR4MUT-CIK groups, respectively, to 110 days in the CD33.CAR+-CXCR4WT-CIK group (p < 0.0001, log-rank test). Taken together, these data show arming CAR-CIK cells with CXCR4 may represent a promising strategy to increase their therapeutic potential for AML.

We postulate that CXCR4 is a potential predictive marker of immunotherapy efficacy in NSCLC and should be used in clinical settings. Moreover, the constructed signatures may be valuable in predicting patient prognosis in NSCLC.

No mutations appeared in the CXCR4 gene until the 58th passage; this may represent important information for studying the CXCR4 pathway as a therapeutic target. Moreover, the CF33 cell line was shown to be able to interact with Salmonella Typhimurium (ST) (an infective stressor), indicating that these cells could be used as an in vitro model for developing innovative therapeutic approaches involving bacteria.

RON knockdown suppressed BC tumor growth in xenograft mouse tumors, accompanied by reduced expression of CXCR4. In conclusion, our data adds evidence that RON, a membrane tyrosine kinase receptor, promotes BC migration and invasion not only by itself, but also by activating MAPK/RSK/CREB signaling pathway to enhance CXCR4 expression.

In conclusion, this study suggests a potential role for CXCR4 in recurrence after trastuzumab-based therapy in human breast cancer that could be mediated, at least in part, by hypoxia and/or decreased ubiquitination. These findings highlight the potential utility of CXCR4 as a promising target for enhancing trastuzumab therapeutic outcome.

Our CXCR4 EC models will allow testing of novel CXCR4-targeted drugs and development of nanomedicines derived from T22-GFP-H6 to deliver drugs to CXCR4 cells in advanced EC. This novel approach provides a therapeutic option for women with metastatic, high risk or recurrent EC that have a dismal prognosis and lack effective therapies.

Collectively, we identified a pre-pubertal condition together with high CXCR4 expression as factors affecting the leukemia permissive testicular microenvironment. We propose CXCR4 as a promising target for therapeutic prevention of testicular relapses in childhood B-ALL.

Further, higher expression of CXCR4 in CAMLs and EMTs was significantly related to faster progression and worse survival. These data suggest that CXCR4 expression in PC is strongly related to the intravasation and presence of TACs into circulation, as well as being a possible biomarker for aggressive metastatic disease.

CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.

The PFH@LSLP was developed to overcome sorafenib resistance by synergistic effects of the following 3 roles: 1) the O-saturated PFH core could alleviate the tumor hypoxia by O supply; 2) the LFC131 peptide recognized the hypoxia-related overexpressed CXCR4 and then blocked SDF-1α/CXCR4 axis to re-sensitize the HCC cells to sorafenib; 3) PLX3397 activated the immune responses via inhibiting the CSF1/CSF1R pathway in TAMs, further enhanced CD8 T cell infiltration to reverse immunosuppression in tumors. Antitumor performance on H22 tumor-bearing mice and HCC patient-derived tumor xenograft (PDX) model showed that PFH@LSLP could overcome sorafenib resistance by synergistic effect of hypoxia attenuation, resistance-related gene regulation, and immune-microenvironment modification.

Co-administration of pioglitazone and doxorubicin might reduce cell migration in breast cancer tumor cells, and that cell migration function is independent of some specific proteins.

The imaging results were validated by histological and immunohistochemical analysis. ProCA32.CXCR4 has strong potential clinical application for non-invasive diagnosis of liver metastases.

In a murine TNBC xenograft model, CXCR4 targeting potently increased tumor regrowth delay following radiation compared to radiation in the presence of pGNPs or vehicle alone. CXCR4 targeted GNPs enhance the efficacy of TNBC radiotherapy by increasing oxidative stress and DNA damage.

212Pb-Pentixather has demonstrated significant radiotherapeutic effect with little renal or bone marrow toxicity in mice bearing SCLC xenografts. Future experiments will explore dose optimization with and without thioredoxin reductase inhibitors to improve therapeutic efficacy and to further reduce renal and bone marrow toxicity.

The delivered miRNAs sensitized GBM cells to temozolomide, resulting in prominent tumor regression, and improved the overall survival of mice. A simple and efficient approach of packaging miRNAs in mpEVs using microfluidics, combined with a noninvasive nose-to-brain delivery route presents far-reaching potential opportunities to improve GBM therapy in clinical practice.

The present study highlighted that high CXCR4 expression is associated with high grade and advanced stage GI-NENs, as well as with metastatic cases. In these cases, high CXCR4 expression could serve as an important target for CXCR4 antagonists.

CXCR4 overexpression promoted proliferation and repressed apoptosis in gefitinib-treated Huh7 cells, which was partly rescued by PHA-665752 (a c-Met inhibitor) treatment or c-Met deficiency. These findings demonstrate that CXCR4 overexpression activates c-Met via the Cav-1 signaling pathway, thereby promoting gefitinib resistance of Huh7 cells. Thus, this study highlights novel insights into the mechanism of gefitinib resistance of HCC, and CXCR4 as a potential target for HCC treatment.

In addition, repeated T22-DITOX-H6 treatment (10 μg/dose per 10 doses, intravenously injected) in a disseminated AML mouse model (NSG mice intravenously injected with THP-1-Luci cells, n = 10 per group) potently blocks the dissemination of AML cells in bone marrow, spleen and liver of treated mice, without inducing toxicity in healthy tissues. In conclusion, our strategy of selectively ablating CXCR4 positive leukemic cells by administering the T22-DITOX-H6 nanoparticle could be a promising treatment, especially in patients undergoing AML relapse after chemotherapy, in which leukemic cells overexpress CXCR4.

Lidocaine at clinical plasma concentrations inhibited CXCL12-induced CXCR4 activation, thereby reduced the intracellular Ca2+-dependent cytoskeleton remodeling, resulting in slower migration of A549 cells.

High CXCR4 expression is clearly associated with increased risk of death and progression in CRC. However, strong methodologic heterogeneity in CXCR4 assessment hinders direct translation into clinical practice; thus, a consensus to streamline detection and scoring of CXCR4 expression in CRC is indicated.