CXCR4 positive

The CXCL12-LD partial agonist effectively mobilized stem cells into the bloodstream in mice suggesting a potential role for their use in targeting CXCR4. Together, our results suggest that enhanced internalization by CXCL12-LD partial agonist signaling can avoid pharmacodynamic tolerance and may identify new avenues to better target GPCRs.

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

Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups...This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

In a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [ Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [ Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.

Among the secretory components, CXCL12, also known as stromal cell-derived factor 1 was accumulated during GBM progression and upregulated in temozolomide (TMZ)-resistant GBM cells compared with parental GBM cell lines... In accordance with the multimodal analysis, GBM regulated the accumulation of CXCL12 via silencing CXCR7 in GBM cells. The CXCR7-CXCL12 axis confers the immunosuppression by up-regulating PD-L1 in GAMs. Our study suggested that CXCR7 activation treatment alone or combined with an immune checkpoint inhibitor may be a potential strategy for the treatment of GBM.

This influence was canceled by pre-treatment with a CXCR4 antagonist. The results of our study suggest that the CXCL12/CXCR4 axis may be associated with the migration of canine MGT.

miR-23a can significantly alleviate sepsis-induced lung injury in CLP-induced septic mice and LPS-stimulated cell lines by suppressing NLRP3 inflammasome activation and inflammatory response, while promoting the CXCR4/PTEN/PI3K/AKT pathway.

Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK CXCR4 CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy.

(4) CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.

In extensive stage SCLC patients, the presence of ≥4 CXCR4-positive CTCs was associated with shorter OS (p = 0.041, HR = 5.01). Consequently, JUNB and CXCR4 were expressed in CTCs from lung cancer patients, and associated with patients' survival, underlying their key role in tumor progression.

We present a case study of a RRMM patient who experienced pseudoprogression twice during his course of disease treatment that included BCMA CAR T cells Idecabtagene vicleucel and GPRC5DxCD3 bispecific antibody talquetamab. We present two educating episodes of pseudoprogression in one patient following immune oncology drugs in MM. While one event was transient and self-limiting, the pulmonary manifestations were similar to sarcoidosis and required treatment with steroids.

The incidence of extramedullary lesions in CXCR4-negative patients increased significantly compared with CXCR4-positive patients. Plasma cells that reduce CXCR4 expression have poor prognosis and increase the incidence of extramedullary lesions.

Recently, 68Ga-pentixafor has been reported as a potential PET imaging agent for CXCR4-positive tumors and inflammatory lesions, including adrenocortical lesions. We report a case of primary aldosteronism due to adrenocortical carcinoma with intense 68Ga-pentixafor activity on PET/CT.

Conditioning regimen was Melphalan...Twenty-seven pts died including 19 pts due to disease progression.  The median OS was 7.8 years. In the study group a statistically significant correlation was found between OS, PFS and the number of CD184+ cells. In the context of OS and PFS, number of CD184+ cells was found to have a negative impact (correlation coefficient R = -0.32, p=0.0261, and correlation coefficient R = -0.41, p=0.0039 for OS and PFS retrospectively).  As OS and PFS increased, the number of CD184+ cells decreased. Conclusion The number of CD184+ cells could have a negative effect on both OS and PFS in multiple myeloma patients.

• We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.

This study further confirms the applicability of PAMAM dendrimers for imaging and therapeutic applications. It also emphasizes careful consideration of image acquisition and/or treatment times when designing dendritic nanoplatforms for tumor targeting.

In patients with solid tumors imaged with [Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.

These data suggest a more suppressive TME in HCC compared to CRLM and highlighted CXCR4 antagonism as a potential strategy to overcome Tregs-mediated TME immunosuppressive function in HCC and CRLM patients.

We discovered, for the first time, that patients with expression of both CXCR-4 and CD133 have a lower survival rate, and CXCR-4+/CD133+, as well as CXCR-4+/PKC-δ+ double positivity, can be utilized to predict poor prognosis. CXCR-4, PKC-δ and CD133 might regulate aggressiveness and invasion of oral cancer cells.

Splenic CXCR4 expression as assessed by [68Ga] -Pentixafor PET was not associated with clinical outcomes of solid cancer patients. However, we demonstrate platelet and / or leucocyte counts to be positively associated with splenic CXCR4 expression in some solid cancer entities. This suggests that splenic CXCR4 expression could possibly be a marker for an activated state of spleen in response to tumor activity in some solid cancer entities.

We developed a copper-64 (t = 12.7 h, 19% beta) labeling route of NOTA-CP01 derived from LY2510924, a cyclopeptide-based CXCR4 potent antagonist, in an attempt to noninvasively visualize CXCR4 expression in metastatic ESCC...The immunofluorescence and immunohistochemistry confirmed the positive expression of CXCR4 in the EC109 tumor and ESCC and metastatic lymph nodes of patients, respectively. We concluded that [Cu]NOTA-CP01 possessed a very high target engagement for CXCR4-positive ESCC and could be a potential candidate in the clinical detection of metastatic ESCC.

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.

SDF-1 dominant model had a higher risk to develop AML, and CXCR4 positive expression predicts poor prognosis in AML patients and it could represent a targeted therapy in AML. In addition, CXCR4 could be easily integrated into the initial routine diagnostic work up of AML.

The hybrid NPs specifically gathered in the bone marrow and released antagomir-188, which promoted osteogenesis and inhibited adipogenesis of BMSCs and thereby reversed age-related trabecular bone loss and decreased cortical bone porosity in mice. Taken together, this study presents a novel way to obtain bone-targeted exosomes via surface display of CXCR4 and a promising anabolic therapeutic approach for age-related bone loss.

Tumoral CXCR4 and CXCL12 were prognostic factors at the univariate and multivariate analysis as for DFS and CSS in PDAC. Stromal PD-L1 stained perineural infiltration and stromal CXCR4 characterized inflammatory cells in the vascular invasion. Thus tumoral and stromal characterization for CXCR4 and CXCL12 in PDAC is worth to identify prognostic categories and to orient therapeutic approach.

These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases. Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.

Furthermore, AMD3100, a specific CXCR4 inhibitor, significantly suppressed HOXB5-mediated CRC metastasis. HOXB5 expression was positively correlated with CXCR4 and ITGB3 expression in human CRC tissues, and patients with positive co-expression of HOXB5/CXCR4, or HOXB5/ITGB3 exhibited the worst prognosis. Our study implicates HOXB5 as a prognostic biomarker in CRC, and defines a CXCL12-HOXB5-CXCR4 positive feedback loop that plays an important role in promoting CRC metastasis.

These results suggest that CXCR4 was expressed in a subset of AML patients and was associated with poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients.

EBV-EBNA1 promotes chemotactic migration of Treg cells via the TGFβ1-SMAD3-PI3K-AKT-c-JUN-miR-200a-CXCL12-CXCR4 axis in the NPC microenvironment. These results suggest that EBV-EBNA1 may serve as a potential therapeutic target to reshape the NPC microenvironment.

CXCR4-positive patients who also expressed SERPINB3 were inclined to suffer from lymph node metastasis, confirming that SERPINB3 is a downstream molecule of CXCR4. CONCLUSIONS In vitro and pathological results showed that SDF-1/CXCR4 activated the NF-kappaB pathway and upregulated SERPINB3 to facilitate the migration and invasion of gastric cancer cells.

A consistent dose response effect for B + E was suggested across all efficacy endpoints for heavily pretreated pts with HER2 negative MBC. When these results are compared with published data for E monotherapy in similar populations, the EC consistently shows numerically greater benefit for all efficacy endpoints 2, 3 . The safety and tolerability of B + E appear comparable to published data on E or B alone, particularly for neutropenia and peripheral neuropathy 1 .

More importantly, LGCC NPs/DOX significantly suppressed the in vitro and in vivo proliferation of CXCR 4 positive hepatocarcinoma and breast cancer. The findings provide a guideline for the combined application of benzylguanidine and other functional groups in antitumor nanomedicines.

Therefore, RhoGDI2 may be a brake for CXCR4-positive T-ALL migration. Because migration is a prerequisite for infiltration of leukemia, this work may suggest the possible involvement of RhoGDI2 in infiltration of T-ALL.