Reconceptualization of immune checkpoint inhibitor-associated gastritis.

In recent years, with the extensive application of immunotherapy in clinical practice, it has achieved encouraging therapeutic effects. While enhancing clinical efficacy, however, it can also cause autoimmune damage, triggering immune-related adverse events (irAEs). Reports of immunotherapy-induced gastritis have been increasing annually, but due to its atypical clinical symptoms, early diag-nosis poses a certain challenge. Furthermore, it can lead to severe complications such as gastric bleeding, elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted. Therefore, gaining a thorough under-standing of the pathogenesis, clinical manifestations, diagnostic criteria, and treatment of immune-related gastritis is of utmost importance for early identification, diagnosis, and treatment. Additionally, the treatment of immune-related gastritis should be personalized according to the specific condition of each patient. For patients with grade 2-3 irAEs, restarting immune checkpoint inhibitors (ICIs) therapy may be considered when symptoms subside to grade 0-1. When restarting ICIs therapy, it is often recommended to use different types of ICIs. For grade 4 irAEs, permanent discontinuation of the medication is necessary.

Prognostic value of atypical B cells in breast cancer.

The impact of tumor-infiltrating B cells on breast cancer (BRCA) outcomes remains poorly understood. Recent findings from Yang et al. identify an atypical, clonally expanded population of activated Fc receptor-like 4 (FCRL4)+ B cells that is associated with improved overall survival in patients affected by various tumor types, including BRCA.

[Development of off-the-shelf universal T cell therapies from ES/iPS cells: applications in cancer and viral infection].

Methods in which patient-derived T cells are genetically modified in vitro and administered to patients have been demonstrated effective in the area of cancer immunotherapy. However, these methods have some unresolved issues such as cost, time, and unstable quality. Several groups have developed strategies to overcome these barriers by regenerating T cells from iPSCs. We have been developing a method in which specific TCR genes are introduced into iPSCs and T cells are regenerated from these iPSCs (TCR-iPSC method). We are now using starting iPSCs from the iPSC stock lines provided by CiRA-F, as the iPSC stock cells are less likely to be rejected. A study aimed at application to solid tumors demonstrated the therapeutic effect of regenerated T cells in a patient tissue xenograft model of WT1 antigen-positive renal cell carcinoma. This article will also discuss strategies by other groups to regenerate various types of T cells from iPSCs.

A new isocoumarin from sponge endophytic fungus Aspergillus ochraceopetaliformis with cytotoxic activity.

A new isocoumarin, 8-hydroxy-3-methyliscoumarin-6-yl acetate (1), was isolated together with five known compounds from sponge endophytic fungus Aspergillus ochraceopetaliformis. The structure of the new compound was established based on 1D and 2D NMR spectral analysis. Compounds 1-6 were evaluated for their cytotoxic activities and antimicrobial activities. Compounds 1 and 6 display cytotoxic activities against mouse melanoma cells B16 with IC50 values 72.5 ± 2.6 and 1.0 ± 0.5 µM, respectively. Compounds 4 and 5 displayed faint antimicrobial activities of Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus.

Assessment of Vicia faba L. Peels: Phytochemical Characterization and Evaluation of Cytotoxic and Antimicrobial Potentials.

The current study intends to reach the optimal use of plant wastes and explore their biological activities. It evaluated the bioactivities and phytoconstituents of 70% methanol extract of Vicia faba L. peels. The results revealed that the extract possessed very potent cytotoxicity against ovarian cancer cell line (SKOV-3) (IC50 =0.01 µg/mL) which exceeds doxorubicin (IC50 =0.95 µg/ml), a reference anticancer agent, potent cytotoxicity against prostate cancer cell line (PC-3) (IC50 =13.60 µg/ml), and moderate cytotoxicity against liver cancer cell line (HepG2) (IC50 = 40.9 µg/ml). Furthermore, the extract exhibited a potent antimicrobial effect on the tested gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis& Micrococcus luteus) with inhibition zone (IZ) range (14.0 - 23.0 mm), gram-negative bacteria (Pseudomonas aeruginosa) (IZ= 14.0 mm), and pathogenic fungal yeast (Candida albicans) (IZ= 19.0 mm). Moreover, 46 phytoconstituents were tentatively identified using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS) in positive ionization mode, 21 phytoconstituents were detected in Vicia faba peel for the first time. High-performance liquid chromatography (HPLC) was used to quantify phenolic compounds, the major compounds were chlorogenic acid, ferulic acid, catechin, and vanillin. In conclusion, plant wastes are a rich source of phytoconstituents that exhibit biological efficacy.

Characterization, biological activity, and anticancer effect of green-synthesized gold nanoparticles using Nasturtium officinale L.

BACKGROUND: Nanostructured materials used have unique properties and many uses in nanotechnology. The most striking of these is using herbal compounds for the green synthesis of nanoparticles. Among the nanoparticle types used for green synthesis, gold nanoparticles (AuNPs) are used for cancer therapy due to their stable structure and non-cytotoxic. Lung cancer is the most common and most dangerous cancer worldwide in terms of survival and prognosis. In this study, Nasturtium officinale (L.) extract (NO), which contains biomolecules with antioxidant and anticancer effects, was used to biosynthesize AuNPs, and after their characterization, the effect of the green-synthesized AuNPs against lung cancer was evaluated in vitro. METHODS: Ultraviolet‒visible (UV‒Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), multiple analysis platform (MAP), and Fourier transform infrared (FT-IR) spectroscopy analyses were performed to characterize the AuNPs prepared from the N. officinale plant extract. Moreover, the antioxidant activity, total phenolic and flavonoid contents and DNA interactions were examined. Additionally, A549 lung cancer cells were treated with 2-48 µg/mL Nasturtium officinale gold nanoparticles (NOAuNPs) for 24 and 48 h to determine the effects on cell viability. The toxicity of the synthesized NOAuNPs to lung cancer cells was determined by the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anticancer effect of the NOAuNPs was evaluated by apoptosis and cell cycle analyses using flow cytometry. RESULTS: The average size of the NPs was 56.4 nm. The intensities of the Au peaks from EDS analysis indicated that the AuNPs were synthesized successfully. Moreover, the in vitro antioxidant activities of the NO and NOAuNPs were evaluated; these materials gave values of 31.78 ± 1.71% and 31.62 ± 0.46%, respectively, in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay at 200 g/mL and values of 25.89 ± 1.90% and 33.81 ± 0.62%, respectively, in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The NO and NOAuNPs gave values of 0.389 ± 0.027 and 0.308 ± 0.005, respectively, in the ferrous ion reducing antioxidant capacity (FRAP) assay and values of 0.078 ± 0.009 and 0.172 ± 0.027, respectively, in the copper ion reducing antioxidant capacity (CUPRAC) assay. When the DNA cleavage activities of NO and the NOAuNPs were evaluated via hydrolysis, both samples cleaved DNA starting at a concentration of 25 g/mL in the cell culture analysis, while the nanoformulation of the NO components gave greater therapeutic and anticancer effects. We determined that the Au nanoparticles were not toxic to A549 cells. Moreover, after treatment with the half-maximal inhibitory concentration (IC50), determined by the MTT assay with A549 cells, we found that at 24 and 48 h, while the necrosis rates were high in cells treated with NO, the rates of apoptosis were greater in cells treated with NOAuNPs. Notably, for anticancer treatment, activating apoptotic pathways that do not cause inflammation is preferred. We believe that these results will pave the way for the use of NOAuNPs in in vitro studies of other types of cancer. CONCLUSION: In this study, AuNPs were successfully synthesized from N. officinale extract. The biosynthesized AuNPs exhibited toxicity to and apoptotic effects on A549 lung cancer cells. Based on these findings, we suggest that green-synthesized AuNPs are promising new therapeutic agents for lung cancer treatment. However, since this was an in vitro study, further research should be performed in in vivo lung cancer models to support our findings and to explain the mechanism of action at the molecular level.

Marine bioactive peptides with anticancer potential, a narrative review.

In this paper, we explore marine bioactive peptides with anticancer potential sourced from various marine organisms, including tunicates, sea sponges, and mollusks. Peptides like Stylisin and Papuamides have been isolated, identified, and modified to enhance their activity, with many advancing to clinical trials due to their diverse biological activities, promising prospects in medicine. Enzymatic hydrolysis is a favored method for extracting peptides from marine proteins, particularly from sponges known for their rich bioactive compounds. Compounds such as Jaspamide and Homophymins exhibit potent cytotoxic activity against cancer cells, underscoring their therapeutic potential. Additionally, peptides from ascidians and mollusks, such as Aplidine and Kahalalide F, demonstrate significant anticancer properties. This study also explores peptides influencing apoptosis, microtubule dynamics, and angiogenesis, providing insights into potential mechanisms for cancer treatment. While peptides like Neovastat and mycothiazole target known pathways, others such as patellamides act through unknown mechanisms, highlighting the intricate interactions of marine peptides with cancer cells. Overall, marine-derived peptides show promise as valuable candidates for developing novel anticancer therapies.

Exploring the seas for cancer cures: the promise of marine-derived bioactive peptide.

Marine environments harbor a wealth of bioactive peptides with potential anticancer properties, sourced from diverse organisms like tunicates, sea sponges, and mollusks. Through isolation, identification, and modification, peptides such as Stylisin and Papuamides have shown enhanced activity and progressed to clinical trials, underscoring their therapeutic promise. Enzymatic hydrolysis emerges as a favored method for peptide extraction from marine proteins, with sponges identified as particularly rich sources. Compounds like Jaspamide and Homophymins exhibit potent cytotoxic activity against cancer cells, highlighting their therapeutic potential. Additionally, peptides from ascidians and mollusks, including Aplidine and Kahalalide F, demonstrate significant anticancer properties. The study delves into peptides affecting apoptosis, microtubule dynamics, and angiogenesis inhibition, offering insights into potential cancer treatment mechanisms. Marine-derived peptides hold great promise as valuable candidates for novel anticancer therapies, with ongoing research aimed at unlocking their full therapeutic benefits.

Assessment of Bryophyllum pinnatum mediated Ag and ZnO nanoparticles as efficient antimicrobial and cytotoxic agent.

Bryophyllum pinnatum is used to cure infections worldwide. Although the flavonoids of this plant are well known, it is still unknown how much of the plant's Ag and ZnO nanoparticles are beneficial. In the current research work, silver and zinc oxide nanoparticles were prepared using Bryophyllum pinnatum extract. The synthesized particles were characterized by UV-visible spectroscopy, SEM, EDS, XRD and FTIR. Synthesized particles were subjected to evaluation of their bactericidal and antifungal activity at various doses. Uv vis spectra at 400 nm corresponding to AgNPs confirmed their synthesis. Strong peaks in the EDS spectra of Ag and ZnO indicate the purity of the sample. The scanning electron microscopic images of ZnONPs showed a size of about 60 nm ± 3 nm, which demonstrated the presence of triangular-shaped ZnO nanoparticles. Green synthesized nanoparticles showed bactericidal activity against both Gram-positive (Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Agrobacterium tumifaciens, Salmonella setubal, Enterobacter aerogenes) strains. AgNPs proved to be more effective against Gram-negative bacterial strains compared to Gram-positive owing to MIC values (10 ppm and 20 ppm respectively). Whereas, ZnONPs were found more effective against Gram-positive bacteria with lower MIC values (10 ppm) as compared to Gram-negative ones (20 ppm). Also, the synthesized nanoparticles exhibited moderate dose-dependent antifungal activity against tested fungal strains ranging from 10 to 70%. Cytotoxicity of nanoparticles was found significant using Brine shrimp's lethality assay with IC50 values of 4.09 ppm for AgNPs, 13.72 ppm for ZnONPs, and 24.83 ppm for plant extract. Conclusively, Ag and ZnO nanoparticles were more effective than plant extract and AgNPs had higher activities than those of ZnONPs. Further research is warranted to explore the precise mechanism of action and the potential applications of these nanoparticles in the medical field.

Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.