Real-world experience with venetoclax-based therapy for patients with myeloid sarcoma.

BACKGROUND: The treatment of myeloid sarcoma (MS) is challenging and has not markedly improved patient prognosis. The introduction of venetoclax (VEN) has changed the treatment of MS, and venetoclax-based therapy has been described as very promising in several case reports. METHODS: In this retrospective study, we analyzed the treatment outcomes of 14 patients with MS treated with venetoclax-based therapy at The First Affiliated Hospital of Xiamen University from January 2020 to October 2023 RESULTS: The cohort consisted of 7 (50%) women and 7 (50%) men with an average age of 37.5 years. Four patients (28.6%) had isolated MS de novo, 2 (14.2%) were diagnosed synchronously with AML, and 8 (57.2%) had isolated extramedullary relapse. The most common sites for MS in our cohort were the skin and lung, followed by the spinal canal, soft tissue, bone and kidney. Five patients were affected at more than three sites. Nine patients received VEN in combination with azacytidine, and 5 patients received VEN in combination with other agents. The median number of venetoclax therapies administered was 2 cycles (range: 1-10 cycles). A response was observed in all patients included in the study, with 8 patients (57.2%) achieving a CR and 3 patients (21.4%) achieving a PR, corresponding to an ORR (including CR and PR) of 78.6%. The median follow-up time for all patients was 13 months (range 1-44 months), and the 1 year OS for all patients was 67.7%. CONCLUSIONS: Venetoclax-based therapy shows excellent efficacy and safety in MS patients in the "real world" at a single institution, and a corresponding prospective study is needed to verify this conclusion.

Stretchable Photonic Crystal-Assisted Glycoprotein Identification for Ovarian Cancer Diagnosis.

Photonic crystals with specific wavelengths can realize surface-enhanced excitation and emission intensities of fluorophores and enhance the fluorescence signals of fluorescent molecules. Herein, stretchable photonic crystals with good mechanochromic properties provide continuously adjustable forbidden wavelengths by stretching to change the lattice spacing, with reflectance peaks blue-shifted up to 110 nm to match indicators of different wavelengths and produce differentiated optical enhancement effects. Glycoproteins are significantly identified as clinical markers. However, the wide participation of glycoproteins in various life processes poses enormous complexity and critical challenges for rapid, facile, high-throughput, and accurate clinical analysis or health assessment. In this work, we proposed a stretchable photonic crystal-assisted glycoprotein identification approach for early ovarian cancer diagnosis. Stretchable photonic crystals can provide rich optical information to efficiently identify glycoproteins in complex matrices. A double-indicator fluorescence sensor was designed to respond to the protein trunk and oligosaccharide segment of glycoproteins separately for improved recognition accuracy. Seven typical glycoproteins could be discriminated from proteins, saccharides, or mixture interferents. Clinical ovarian cancer samples for early, intermediate, and advanced ovarian cancer and healthy subjects were verified with 100% accuracy. This strategy of stretchable photonic crystal-assisted glycoprotein identification provides an effective method for accurate, rapid ovarian cancer diagnosis and timely clinical treatment.

SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells.

BACKGROUND: Acute myeloid leukemia (AML) is a highly aggressive form of cancer that is frequently diagnosed in adults and small molecule inhibitors have gained significant attention as a potential treatment option for AML. METHODS: The up-regulated genes in AML were identified through bioinformatics analysis. Potential candidate agents were selected through pharmacogenomics analysis. Proteomic experiments were conducted to determine the molecular mechanism after inhibitor treatment. To evaluate drug synergy, both cellular functional experiments and an AML mouse model were used. RESULTS: Through bioinformatics analysis, we conducted a screening for genes that are highly expressed in AML, which led to the identification of nine small-molecule inhibitors. Among these inhibitors, the PI3K/mTOR inhibitor VS-5584 demonstrated significant effectiveness in inhibiting AML cell proliferation at low concentrations. Further testing revealed that VS-5584 induced apoptosis and cycle arrest of AML cells in a dose- and time-dependent manner. Proteomics analysis showed significant changes in protein expression profiles of AML cells after VS-5584 treatment, with 287 proteins being down-regulated and 71 proteins being up-regulated. The proteins that exhibited differential expression were primarily involved in regulating the cell cycle and apoptosis, as determined by GO analysis. Additionally, KEGG analysis indicated that the administration of VS-5584 predominantly affected the P53 and SIRT2 signaling pathways. The use of SIRT2 inhibitor SirReal2 alongside VS-5584 caused a significant reduction in the half-maximal inhibitory concentration (IC50 ) of VS-5584 on AML cells. In vivo, experiments suggested that VS-5584 combined with SirReal2 suppressed tumor growth in the subcutaneous model and extended the survival rate of mice injected with tumor cells via tail vein. CONCLUSIONS: Taken together, the PI3K/mTOR inhibitor VS-5584 was effective in suppressing AML cell proliferation. PI3K/mTOR inhibitor combined with SIRT2 inhibitor exhibited a synergistic inhibitory effect on AML cells. Our findings offer promising therapeutic strategies and drug candidates for the treatment of AML.

Bioreduction mechanisms of high-concentration hexavalent chromium using sulfur salts by photosynthetic bacteria.

Eliminating "sulfur starvation" caused by competition for sulfate transporters between chromate and sulfate is crucial to enhance the content of sulfur-containing compounds and improve the tolerance and reduction capability of Cr(VI) in bacteria. In this study, the effects of sulfur salts on the Cr(VI) bioremediation and the possible mechanism were investigated in Rhodobacter sphaeroides SC01 by cell imaging, spectroscopy, and biochemical measurements. The results showed that, when the concentration of metabisulfite was 2.0 g L-1, and the initial OD600 was 0.33, the reduction rate of R. sphaeroides SC01 reached up to 91.3% for 500 mg L-1 Cr(VI) exposure at 96 h. Moreover, thiosulfate and sulfite also markedly increased the concentration of reduced Cr(VI) in R. sphaeroides SC01. Furthermore, the characterization results revealed that -OH, -CONH, -COOH, -SO3, -PO3, and -S-S- played a major role in the adsorption of Cr, and Cr(III) reduced by bacteria was bioprecipitated in the production of Cr2P3S9 and CrPS4. In addition, R. sphaeroids SC01 combined with metabisulfite significantly increased the activity of glutathione peroxidase and the content of glutathione (GSH) and total sulfhydryl while decreasing reactive oxygen species (ROS) accumulation and cell death induced by Cr(VI) toxic. Overall, the results of this research revealed a highly efficient and reliable strategy for Cr(VI) removal by photosynthetic bacteria combined with sulfur salts in high-concentration Cr(VI)-contaminated wastewater.

Synthesis of C3-sulfone substituted naphthols via rhodium(III)-catalyzed annulation of sulfoxonium ylides with alkynylsulfones.

C-H activation of sulfoxonium ylides catalyzed by rhodium(iii) with subsequent annulation by alkynylsulfones was accomplished. This methodology offers a step-economical approach for assembling C3-sulfone-substituted naphthols with a high level of regioselectivity that is complementary to previous protocols. The approach has an extensive substrate spectrum and broad functional group tolerance.