In vivo evaluation of mebendazole and Ran GTPase inhibition in breast cancer model system.

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.

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Flow cytometric signature of CD371-positive B-cell acute lymphoblastic leukemia.

OBJECTIVES: Multiparametric flow cytometry (MFC) aids in the diagnosis and management of B-cell acute lymphoblastic leukemia (B-ALL) by establishing a baseline immunophenotype for leukemic cells and measuring minimal residual disease (MRD) throughout the course of treatment. Aberrant expression patterns of myeloid markers in B-ALL are also examined during long-term surveillance. Here, we investigated the utility of the newly described myeloid marker cluster of differentiation (CD)371 in MRD surveillance via MFC in patients with CD371-positive B-ALL. METHODS: Eight-color MFC with standard panels (including CD371) was used to evaluate 238 patients with newly diagnosed B-ALL. Expression levels of key markers were retrospectively assessed at diagnosis, as well as days 15 and 33 of therapy. RESULTS: CD371 was expressed in 8.4% of patients with B-ALL. CD371 positivity was associated with older age at diagnosis, higher expression levels of CD34 and CD38, and lower expression levels of CD10 and CD20. Residual leukemic cells demonstrated decreased CD10 expression and increased CD45 expression after therapy, whereas CD371 expression remained stable. CONCLUSIONS: Patients with CD371-positive B-ALL exhibit a specific signature that merits further analysis, particularly because it has been associated with DUX4 rearrangement.

PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients.

Anti-programmed death-ligand 1 (PD-L1) treatments can improve colorectal carcinoma (CRC) survival; however, there is still controversy regarding the relationship between PD-L1 expression and the outcome of immunotherapeutic treatment and survival. The discrepancies are partly caused by the lack of a unified scoring system. This retrospective, cross-sectional study evaluated PD-L1 by immunohistochemistry in 127 CRC cases and compared the 3 scoring systems used to assess PD-L1: Tumor Percentage Score (TPS), Combined Positive Score (CPS), and immune cell (IC) score. Correlations were calculated using the χ 2 test. Kaplan-Meier curves with the Log-rank test were used to measure the contribution of PD-L1 expression to survival. PD-L1-positive rate were 29.9%, 57.5%, and 55.9% based on TPS, CPS, and IC score, respectively. TPS showed a better correlation with the clinicopathologic features being significantly higher with young age, T4, and adenocarcinomas (compared with mucinous/signet ring). TPS also showed an increasing trend with higher grade, lymph node stage, and male sex, although these variables were not significantly associated with PD-L1 expression. There was no correlation between PD-L1 expression and mismatch repair protein status in the 3 scoring methods. The probability of survival was higher for PD-L1-negative cases in the first 60 months after surgery if scored by the TPS method ( P =0.058). Future efforts correlating PD-L1 status with response to treatment are needed to decide on the best scoring method to be used for making therapy decisions.

A case of malignant glomus tumor (glomangiosarcoma) of the nasal cavity.

Glomus tumors are rare and usually benign. The malignant form (glomangiosarcoma) comprises <1% of all glomus tumors. There are limited reports that describe glomus tumors in the nasal cavity. However, to the best of our knowledge, glomangiosarcoma of the nasal cavity was never reported in humans. We report on the first case of nasal cavity glomangiosarcoma in a 59-year-old male who presented with a bleeding mass in his right nostril. We completely excised the lesion with a 0.7-mm free margin, and the histopathologic examination was consistent with glomangiosarcoma. A 6-month follow-up illustrated no evidence of recurrence or distant metastasis. Although it is rare, glomus tumors should be in the differential diagnosis of nasal cavity tumors. Histopathologic examination is essential for glomangiosarcoma diagnosis. Treatment requires complete excision with free margin, alongside careful clinical and radiological follow-up.

Diffuse midline glioma H3 K27M-mutant in adults: A report of six cases and literature review.

AIM: Diffuse midline glioma (DMG) H3 K27M-mutant is a specific entity that, as the name indicates, tends to occur in midline structures including the thalamus, brainstem, and spinal cord. DMG predominates in children, is an aggressive tumor with poor prognosis, and is considered a WHO grade IV tumor regardless of histological features. The exact frequency of these mutations in adults diagnosed with glioma in the midline is unknown. MATERIALS AND METHODS: We report a series of 6 more adult cases, and we critically review the current literature on adults with DMG H3 K27M-mutant. RESULTS: There were 5 males and 1 female. The age ranged from 26 to 52 years (median 39 years). All cases showed astrocytic differentiation, with positive staining for H3 K27M protein, and loss of H3 K27me in the tumor cells confirming the diagnosis. CONCLUSION: H3 K27M-mutant midline glioma can occur in adults, affecting midline structures. Increasing awareness of the reporting pathologists of this entity might help in a better determination of the frequency of mutant DMG in adults as well as better diagnosis and patient counseling of the outcome.