Topical gel formulations as potential dermal delivery carriers for green-synthesized zinc oxide nanoparticles.

This study aimed to incorporate green-synthesized zinc oxide nanoparticles (ZnO NPs), functionalized with polyethylene glycol (PEG) and linked to doxorubicin (DOX), into various topical gel formulations (hydrogel, oleogel, and bigel) to enhance their dermal delivery. The ZnO NPs were produced using the aqueous extract of the root hair of Phoenix dactylifera. The optimized green-synthesized ZnO NPs, PEGylated and conjugated to DOX, demonstrated a particle size below 100 nm, low polydispersity index, and zeta potential between - 11 and - 19 mV. The UV-Vis spectroscopy analysis confirmed characteristic absorption peaks at 351 and 545 nm for ZnO and DOX, respectively. The transmission electron microscope (TEM) images revealed well-dispersed spherical nanoparticles without aggregation. Additionally, ZnO NPs-loaded gels exhibited uniformity, cohesion, no phase separation, pseudoplastic flow, and viscoelastic properties. The in vitro release studies showed that DOX-PEG-ZnO NPs hydrogel released 99.5% of DOX after 5 h of starting the release. Moreover, the penetration of DOX-PEG-ZnO NPs through excised rat skin was visualized by TEM. In conclusion, the hydrogel formulation containing green-synthesized DOX-PEG-ZnO NPs holds great promise for dermal administration in skin cancer treatment. Furthermore, the release rate and skin penetration of DOX from gels were varied based on the type of gel matrix and corroborated with their corresponding rheological properties.

A three-marker signature identifies senescence in human breast cancer exposed to neoadjuvant chemotherapy.

PURPOSE: Despite the beneficial effects of chemotherapy, therapy-induced senescence (TIS) manifests itself as an undesirable byproduct. Preclinical evidence suggests that tumor cells undergoing TIS can re-emerge as more aggressive divergents and contribute to recurrence, and thus, senolytics were proposed as adjuvant treatment to eliminate senescent tumor cells. However, the identification of TIS in clinical samples is essential for the optimal use of senolytics in cancer therapy. In this study, we aimed to detect and quantify TIS using matched breast cancer samples collected pre- and post-exposure to neoadjuvant chemotherapy (NAC). METHODS: Detection of TIS was based on the change in gene and protein expression levels of three senescence-associated markers (downregulation of Lamin B1 and Ki-67 and upregulation of p16INK4a). RESULTS: Our analysis revealed that 23 of 72 (31%) of tumors had a shift in the protein expression of the three markers after exposure to NAC suggestive of TIS. Gene expression sets of two independent NAC-treated breast cancer samples showed consistent changes in the expression levels of LMNB1, MKI67 and CDKN2A. CONCLUSIONS: Collectively, our study shows a more individualized approach to measure TIS hallmarks in matched breast cancer samples and provides an estimation of the extent of TIS in breast cancer clinically. Results from this work should be complemented with more comprehensive identification approaches of TIS in clinical samples in order to adopt a more careful implementation of senolytics in cancer treatment.

Rapidly progressive glomerulonephritis due to systemic lupus erythematosus and ANCA-associated vasculitis overlap.

Systemic lupus erythematosus (SLE) and ANCA-associated vasculitis (AAV) are different autoimmune diseases. While vasculitis can be seen in the SLE clinical course as a secondary phenomenon, and may indicate a severe disease, primary vasculitis such as AAV rarely occurs in association with SLE. We present a 44-year-old woman who presented with rapidly progressive glomerulonephritis which was histologically identified as a combination of crescentic and lupus nephritis in the presence of myeloperoxidase ANCA antibody. The frequency of this association is very rare. The clinical, histological and immunological features are different in SLE/AAV overlap syndrome and need different treatment options, which may include rituximab, to achieve complete recovery. Since SLE/AAV overlap can be serious at presentation, the physician must be aware of this syndrome.

Primary alveolar rhabdomyosarcoma of fallopian tube masquerading as a unilateral adnexal mass: A case report and literature review.

Rhabdomyosarcoma (RMS) is a high-grade sarcoma that predominantly affects children, and rarely, the adult population. RMS demonstrates three major histologic variants: Embryonal, alveolar, and pleomorphic. A limited number of documented pure RMS cases of the gynecologic organs in adult women are found in the literature. Of these reports, the fallopian tube (FT) is reported as the primary site in only three cases, those included one of embryonal and two of the pleomorphic histologic variants. Herein, we report the first case of alveolar RMS arising in the FT of an adult woman and presenting as a unilateral adnexal mass.

MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers.

PURPOSE: Expression of the PGE2 receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known. The present study was conducted to investigate the regulation of EP4 receptor by miRNAs. EXPERIMENTAL DESIGN: We analyzed 26 colon cancers (i.e. 15 adenocarcinomas and 9 adenomas) and 16 normal colon specimens for EP4 receptor expression by immunohistochemistry. A bioinformatics approached identified putative microRNA binding sites with the 3'-UTR of the EP4 receptor. Both colon cancer cell lines and tumor specimens were analyzed for miR-101 and EP4 expression by qRT-PCR and Western analysis respectively and simultaneously in situ hybridizations was used to confirm our results. In vitro and in vivo assays were used to confirm our clinical findings. RESULTS: We observed an inverse correlation between the levels of miR-101 and EP4 receptor protein. Transfection of LS174T cells with miR-101 significantly suppressed a luciferase reporter containing the EP4 receptor-3'-UTR. In contrast, a mutant EP4 receptor-3'-UTR construct was unaffected. Ectopic expression of miR-101 markedly reduced cell proliferation and motility. Co-transfection of EP4 receptor could rescue colon cancer cells from the tumor suppressive effects of miR-101. Moreover, the pharmacologic inhibition of EP4 receptor signaling or silencing of EP4 receptor phenocopied the effect of miR-101. This is the first study to show that the EP4 receptor is negatively regulated by miR-101. CONCLUSIONS: These data provide new insights in the modulation of EP-4 receptor expression at the post-transcriptional level by miR-101 and suggests therapeutic strategies against miR-101 targets may be warranted.