Image_1_Case report: Temozolomide induced hypermutation: an indicator associated with immunotherapy response in patient with gliomas.jpeg

BackgroundTemozolomide (TMZ) is a key component in the treatment of gliomas. Hypermutation induced by TMZ can be encountered in routine clinical practice, and its significance is progressively gaining recognition. However, the relationship between TMZ-induced hypermutation and the immunologic response remains controversial.Case presentationWe present the case of a 38-year-old male patient who underwent five surgeries for glioma. Initially diagnosed with IDH-mutant astrocytoma (WHO grade 2) during the first two surgeries, the disease progressed to grade 4 in subsequent interventions. Prior to the fourth surgery, the patient received 3 cycles of standard TMZ chemotherapy and 9 cycles of dose-dense TMZ regimens. Genomic and immunologic analyses of the tumor tissue obtained during the fourth surgery revealed a relatively favorable immune microenvironment, as indicated by an immunophenoscore of 5, suggesting potential benefits from immunotherapy. Consequently, the patient underwent low-dose irradiation combined with immunoadjuvant treatment. After completing 4 cycles of immunotherapy, the tumor significantly shrank, resulting in a partial response. However, after a 6-month duration of response, the patient experienced disease progression. Subsequent analysis of the tumor tissue obtained during the fifth surgery revealed the occurrence of hypermutation, with mutation signature analysis attributing TMZ treatment as the primary cause. Unfortunately, the patient succumbed shortly thereafter, with a survival period of 126 months.ConclusionPatients subjected to a prolonged regimen of TMZ treatment may exhibit heightened vulnerability to hypermutation. This hypermutation induced by TMZ holds the potential to function as an indicator associated with unfavorable response to immunotherapy in gliomas.</p

Table_1_Case report: Temozolomide induced hypermutation: an indicator associated with immunotherapy response in patient with gliomas.docx

BackgroundTemozolomide (TMZ) is a key component in the treatment of gliomas. Hypermutation induced by TMZ can be encountered in routine clinical practice, and its significance is progressively gaining recognition. However, the relationship between TMZ-induced hypermutation and the immunologic response remains controversial.Case presentationWe present the case of a 38-year-old male patient who underwent five surgeries for glioma. Initially diagnosed with IDH-mutant astrocytoma (WHO grade 2) during the first two surgeries, the disease progressed to grade 4 in subsequent interventions. Prior to the fourth surgery, the patient received 3 cycles of standard TMZ chemotherapy and 9 cycles of dose-dense TMZ regimens. Genomic and immunologic analyses of the tumor tissue obtained during the fourth surgery revealed a relatively favorable immune microenvironment, as indicated by an immunophenoscore of 5, suggesting potential benefits from immunotherapy. Consequently, the patient underwent low-dose irradiation combined with immunoadjuvant treatment. After completing 4 cycles of immunotherapy, the tumor significantly shrank, resulting in a partial response. However, after a 6-month duration of response, the patient experienced disease progression. Subsequent analysis of the tumor tissue obtained during the fifth surgery revealed the occurrence of hypermutation, with mutation signature analysis attributing TMZ treatment as the primary cause. Unfortunately, the patient succumbed shortly thereafter, with a survival period of 126 months.ConclusionPatients subjected to a prolonged regimen of TMZ treatment may exhibit heightened vulnerability to hypermutation. This hypermutation induced by TMZ holds the potential to function as an indicator associated with unfavorable response to immunotherapy in gliomas.</p

One-Pot Synthesis of Mesoporous Silica Nanocarriers with Tunable Particle Sizes and Pendent Carboxylic Groups for Cisplatin Delivery

Mesoporous silica nanocarriers with tunable particle sizes and different loadings of pendent carboxylic groups were successfully prepared by a straightforward and reproducible strategy, in which carboxyethylsilanetriol sodium salt was co-condensed with tetraethoxyorthosilicate to introduce the carboxylic groups. The key in this strategy was to separate the synthesis process into two steps of the nuclei formation and particle growth. The uniform particle size and ordered structure of the synthesized nanocarriers were manifested by several techniques such as XRD, TEM, SEM, and BET. DLS measurement illustrated that nanocarriers could be well suspended in aqueous solution. The integration and content tunability of the carboxylic groups within mesoporous silica nanoparticles (MSNs) were verified by FT-IR and ²⁹Si NMR. The inherent carboxylic units on the obtained carboxylic group modified MSNs (MSNs-C) effectively enhanced the capture and tailored the release properties of the anticancer drug of cisplatin. The accumulation of drug in the HeLa cells was greatly enhanced due to the highly efficient platinum uptake efficiency transported by the synthesized nanocarriers. The drug encapsulated in the MSNs-C exhibited a higher antitumor activity than free cisplatin against both MCF-7 and HeLa cells

Water Splitting with an Enhanced Bifunctional Double Perovskite

The rational design of highly active and durable electrocatalysts for overall water splitting is a formidable challenge. In this work, a double perovskite oxide, i.e., NdBaMn₂O_5.5, is proposed as a bifunctional electrode material for water electrolysis. Layered NdBaMn₂O_5.5 demonstrates significant improvement in catalyzing oxygen and hydrogen evolution reactions (OER and HER, respectively), in contrast to other related materials, including disordered Nd_0.5Ba_0.5MnO_3−δ as well as NdBaMn₂O_5.5−δ and NdBaMn₂O_5.5+δ (δ < 0.5). Importantly, NdBaMn₂O_5.5 has an OER intrinsic activity (∼24 times) and a mass activity (∼2.5 times) much higher than those of the benchmark RuO₂ at 1.7 V versus the reversible hydrogen electrode. In addition, NdBaMn₂O_5.5 achieves a better overall water splitting activity at large potentials (>1.75 V) and catalytic durability in comparison to those of Pt/C–RuO₂, making it a promising candidate electrode material for water electrolyzers. The substantially enhanced performance is attributed to the approximately half-filled e_g orbit occupancy, optimized O p-band center location, and distorted structure. Interestingly, for the investigated perovskite oxides, OER and HER activity seem to be correlated; i.e., the material achieving a higher OER activity is also more active in catalyzing HER