CXCR4 expression

MALAT1 silencing may repress CXCL12 induction on MM cell proliferation, invasion, and homing behavior by inhibiting CXCR4. MALAT1 may be a promising target for MM treatment.

Targeting CXCR4 with [64Cu]Cu-NOTA-CP01 for PET imaging of lymph nodes metastasis represents a promising approach that warrants further investigation. These findings have the potential to enhance diagnostic and therapeutic strategies for individuals with lymph nodes metastasis of ESCC.

Their expression can be recovered at later time-points, suggesting the presence of a negative feedback loop mechanism. In contrast, late response genes, which are continuously downregulated after MYB depletion, includes many genes involved in cell proliferation as well as TAL1 targets, thereby affecting the cellular phenotype.

Huayu Jiedu Decoction can inhibit the proliferative activity of U266 cells and induce programmed death. Its molecular mechanism may be related to regulating the expression of apoptotic proteins, inhibiting the activation of TLR4/NF-κB pathway and down-regulating the expression of HMGB1 and IL-6 mRNA.

Our research suggests that the complex interactions between CXCL12 and the various tumor and immune cell types contributes not only to the completion of the initial steps of the metastatic cascade, but also offers an immunological "sanctuary" to prometastatic tumor cells homed around TMEM doorways. Overall, our study enhances our current understanding on the mechanisms, via which CXCL12 orchestrates tumor cell behavior and immune dynamics, potentially guiding future thera- peutic strategies to combat breast cancer metastasis and improve anti-tumor immunity.

Besides, fused in sarcoma (FUS) was confirmed to bind to USP1 and stabilized its mRNA expression, and could regulate CXCR4 via USP1. In conclusion, USP1 stabilized CXCR4 by removing ubiquitination on CXCR4, thereby promoting ESCC cell proliferation, invasion, and immune escape in vitro, and tumor growth in vivo.

MIP-1α expression was significantly correlated with average CXCR4 CAML expression (P = 0.003). We discovered larger CAML size was associated with SAT-dominant obesity with increased macrophage-related and proinflammatory markers in obese than in nonobese breast cancer patients.

In conclusion, our comprehensive investigation highlights CXCR4 as a key mediator of TME dynamics and immune modulation in GC. Targeting CXCR4 presents a promising therapeutic strategy to slow tumor progression by reducing Tregs-mediated immune exhaustion and TME heterogeneity, positioning it as a novel therapeutic target in GC treatment.

Preclinical and pilot clinical studies demonstrated its feasibility and potential application in precise diagnosis for not only lymphoma but also SCLC and glioma. [18F]AlF-NOTA-QHY-04 PET/CT can also provide a complementary mapping for brain tumors to [18F]FDG PET/CT.

Selective p53 knockdown led to positive therapeutic outcomes in mice with cisplatin-induced AKI, as seen by reduced tubular cell death, renal injury, inflammation, and overall improved renal function. These findings indicate that IC is a promising new carrier for renal-targeted delivery of RNA for the treatment of AKI.

Inhibition of CXCR4 expression also reduced the invasion of cancer cells by CXCL12. In conclusion, our results suggest that ISO is a novel inhibitor to regulate CXCR4 expression and the key molecule contributing to antitumor activity.

We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients.

Notably, clinical sample analysis revealed that CXCR4+CD8+ T cells showed higher expression in patients with a non-complete pathological response. Collectively, these findings demonstrate the mechanism by which CXCR4 orchestrates CD8+ Tex cells and provide a rationale for combining CXCR4 antagonists with immunotherapy in clinical trials.

Altogether, these results suggest that in vitro ACKR3 plays a minor role in malignant GBM cell biology and that its expression is possibly regulated by in-vivo influences. The subtle and multifaceted functions ACKR3 could exert in GBM should therefore only be tackled within a comprehensive tumor microenvironment considering tumoral but also non-tumoral cells.

HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

CXCL9 + macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7 + HLA-E HIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Our findings suggest that, when assessing the prognostic significance of CXCL12 in HCC, it is essential to consider the expression level of its receptor. Nevertheless, CXCL12 can potentially serve as a promising prognostic marker for HCC.

Finally, CD44 targeting can be a good treatment option to make BC cells more sensitive to apoptosis.

R54 impairs Tregs function in primary RCC patients targeting PTEN/PI3K/AKT pathway, reducing TSDR demethylation and FOXP3 and DNMT1 expression. Thus, CXCR4 targeting is a strategy to inhibit Tregs activity in the RCC tumour microenvironment.

Anti-cancer and cytotoxic effects of metformin can be effective in this strategy. In conclusion, the combination of conventional chemotherapeutic drugs, including SB203580, metformin, and takinib with X-ray exposure can be a new approach to diminish the drug resistance of breast cancer.

Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity. These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.

P3, N=148, Not yet recruiting, Pentixapharm AG | Initiation date: Dec 2023 --> May 2024

P=N/A, N=35, Active, not recruiting, Monash Health - Department of Endocrinology | Recruiting --> Active, not recruiting | N=20 --> 35

In vitro and in vivo assessments demonstrated the CXCR4-dependent, specific, and sensitive uptake of [18F]SFB-AMD3465 in the CXCR4-overexpressing 4T1 cell line and the corresponding xenograft-bearing mouse model. These findings contribute to bridging the gap in 18F-labeled PET tracers for CXCR4 and underscore the potential of [18F]SFB-AMD3465 as a PET radiotracer for in vivo CXCR4 imaging.

The findings of this study showed a robust association between elevated levels of CXCR4, CXCL12, CCL2, CXCL8, CXCL10 and CXCR7 with a higher risk of glioma. Furthermore, the WHO grading system was validated by the strong correlation shown between higher expression of CXCR4, CXCL12, CCL2, and CCL18 and WHO high-grade gliomas (grades 3-4). Furthermore, the results of the meta-analysis suggested that CXCR4 might be a helpful biomarker for predicting the worse prognosis of glioma patients.

CXCR4 might be a potential biomarker for the progress and prognosis evaluation, and therapeutic target for ESCC.

The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.

When applied to antagonize chemokine receptors CXCR4 expressed in metastatic breast cancer of female mice, this strategy elicits and consolidates multiple events, including interception of metastatic cascade, reversal of immunosuppression, and potentiation of photodynamic immunotherapy, reducing the metastatic burden. Collectively, our work provides a generalizable tool to spatially rearrange cell-surface receptors to improve therapeutic outcomes.

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

Local administration of hybrid nanovesicles also induced an abscessive effect in a bilateral 4T1 tumor model. This study demonstrates a promising biomimetic manganese/doxorubicin-based hybrid nanovesicle platform for effective cancer immunotherapy tailored to the tumor microenvironment, which may offer an innovative approach to combinatorial immunotherapy.

The second generation D-peptide AlF-NOTA-2xDV1(c11sc12s) showed high affinity for human CXCR4 and the corresponding radiotracer was produced in good radiochemical yields. However, [18F]AlF-NOTA-2xDV1(c11sc12s) is not specific for CXCR4 and is also a substrate for OATP1B1 and/or OATP1B3, known to mediate hepatic uptake. Therefore, D-amino acid peptides, based on the viral macrophage inflammatory protein II, are not the prefered vector molecule for the development of CXCR4 targeting molecular imaging tools.

Moreover, our study pinpointed that infiltrated CXCR4hi neutrophils, regardless of their differential distribution of cell maturation status in HB tumor and para-tumor regions, were the genuine perpetrators for immune suppression. Our data characterized the ferroptosis-dependent immunosuppression energized by intratumoral CXCR4 expression neutrophils and suggest a potential cell target for cancer immunotherapies.

Our data indicate that the RUNX2 transcription factor promotes the expression of the CXCR4 chemokine receptor on melanoma cells, which in turn promotes autophagy, cell invasiveness, and osteotropism, through the inhibition of the mTOR signalling pathway. Our data suggest that RUNX2 promotes melanoma progression by upregulating CXCR4, and we identify the latter as a key player in melanoma-related osteotropism.

Finally, analysis of multiple CCL chemokines in the macrophage secretome revealed that CXCR4 inactivation and CXCR7 activation selectively enhanced P2Y11/IL-1R-mediated secretion of CCL20. Altogether, our data establish CXCR7 as an integral component of the P2Y11/IL-1R-initiated signaling cascade and CXCR4-associated PDE4 as a regulatory checkpoint.

At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC.

These studies also provide convincing evidence that inhibition of CXCL12/CXCR4 signalling during or after RT can reduce or prevent RT side effects, warranting further evaluation in clinical studies. Greater dialogue with the pharmaceutical industry is needed to prioritize the development and availability of CXCL12/CXCR4 inhibitors for future RT studies.

P=N/A, N=60, Recruiting, Xiao Chen | Not yet recruiting --> Recruiting

Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

P=N/A, N=90, Not yet recruiting, University Hospital, Bordeaux

P=N/A, N=60, Not yet recruiting, Xiao Chen

P1, N=8, Completed, AdAlta Limited | Not yet recruiting --> Completed | N=16 --> 8 | Trial completion date: Jul 2024 --> Feb 2024 | Trial primary completion date: Jul 2024 --> Feb 2024

Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.