Sophoridine, an alkaloid quinolizidine derived from Sophora flavescens Aiton (Fabaceae), has strong anti-tumor activity in a variety of malignancies. Nevertheless, the effects and underlying mechanism of sophoridine on breast cancer are not fully understood.

To identify the key targets and potential pharmacological mechanisms of sophoridine against breast cancer.

MCF-10A, MCF-7 and MDA-MB-231 cells were treated with sophoridine for 24 or 48 h. MTT, colony formation assay, flow cytometry, wound healing, and Transwell assay were employed to illustrate the anti-tumor effects of sophoridine on breast cancer. Network pharmacology and molecular docking were used to determine the targets for sophoridine in breast cancer, and confirmed by molecular dynamics simulation and CETSA-western blot assay. Additionally, the functional rescue and signaling pathway regulated by sophoridine was analyzed.

Sophoridine suppressed the proliferation, migration, and invasion of breast cancer cells. The IC₅₀ value of sophoridine for 48 h in MCF-10A, MCF-7 and MDA-MB-231 was 363 μM, 87.96 μM and 81.07 μM, respectively. PIM1 was the key target for sophoridine in breast cancer. Furthermore, PIM1 overexpression significantly reversed the suppressive impacts of sophoridine on growth and migration in breast cancer cells. Mechanistically, sophoridine inhibited the phosphorylation of ASK1 and activated JNK/p38 MAPK signaling pathway by downregulating PIM1 expression, and thus exhibited anti-tumor effects.

Taken together, sophoridine relies on targeting PIM1 to inhibit cell proliferation and migration in breast cancer, which might be related to the activation of ASK1/MAPK axis, suggesting the therapeutic potential of sophoridine for breast cancer.

Pancreatic cancer is a highly malignant tumor with poor prognosis and limited treatments. Immunotherapy shows promise in improving outcomes, but bibliometric analyses in this field are scarce. Our work reveals emerging trends, identifies research gaps, and highlights shifts in focus, offering valuable guidance for future research of immunotherapy and clinical practice. Pancreatic cancer immunotherapy bibliometric analyses were performed utilizing tools such as CiteSpace, VOSviewer, and RStudio, with a focus on the temporal and spatial distribution, prominent authors, research themes, keywords, and citation networks. The analysis reveals a significant increase in research activity on pancreatic cancer immunotherapy over the past decade, with hotspots including ICIs, CAR-T therapy, novel biomarkers, targeted therapies, the tumor microenvironment, and personalized treatment strategies. This study systematically reviews pancreatic cancer immunotherapy research progress from 1991 to 2024, highlighting key hotspots and trends. Future efforts should focus on ICIs, CAR-T therapy, and combination strategies, to enhance outcomes and extend patient survival.

Design of T cell receptors by artificial intelligence is poised to accelerate cancer immunotherapy.

T cell receptor (TCR) mimics offer a promising platform for tumor-specific targeting of peptide-major histocompatibility complex (pMHC) in cancer immunotherapy. In this study, we designed a de novo α-helical TCR mimic (TCRm) specific for the NY-ESO-1 peptide presented by human leukocyte antigen (HLA)-A*02, achieving high on-target specificity with nanomolar affinity (dissociation constant K_d = 9.5 nM). The structure of the TCRm-pMHC complex at 2.05-Å resolution revealed a rigid TCR-like docking mode with an unusual degree of focus on the up-facing NY-ESO-1 side chains, suggesting the potential for reduced off-target reactivity. Indeed, a structure-informed in silico screen of 14,363 HLA-A*02 peptides correctly predicted two off-target peptides, yet our TCRm maintained peptide selectivity and cytotoxicity as a T cell engager. These results represent a path for precision targeting of tumor antigens with peptide-focused α-helical TCR mimics.

Mutant RAS proteins are among the most prevalent drivers of human cancer, and the glycine to aspartic acid mutation at codon 12 (G12D) is the most common variant. Mutation-selective covalent inhibitors spare RAS in healthy tissue and enable extended pharmacodynamic effect, but covalent targeting of RAS^G12D is hindered by low nucleophilicity and high proteomic abundance of carboxylic acids. We overcame these challenges with compounds that bind cyclophilin A (CYPA) to create a neomorphic protein-protein interface between CYPA and active RAS that enables selective, enzyme-like rate enhancement of the covalent reaction between D12 and electrophilic warheads with exceptionally low intrinsic reactivity. This approach yielded orally bioavailable compounds with marked antitumor activity in multiple preclinical models of KRAS^G12D cancers, including the investigational agent zoldonrasib (RMC-9805) currently undergoing clinical evaluation (NCT06040541).

To evaluate the potential use of a combination of subretinal triamcinolone acetonide (TA) injection with transpupillary thermotherapy (TTT) in the treatment of circumscribed choroidal hemangioma (CCH) with exudative retinal detachment.

The clinical case of a 27-year-old patient demonstrates the treatment of CCH with exudative retinal detachment. We used a combination of subretinal injection of 4 mg preservative-free TA with the simultaneous partial aspiration of subretinal fluid in the first stage. After one week, when the retina was fully attached, TTT of CCH was used in the second stage. At Month 12, visual acuity in the left eye increased from light perception with projection to 20/400. Ultrasonography did not reveal any signs of choroidal masses or retinal detachment. During the follow-up period, 3 sessions of TTT were performed.

A combination of subretinal TA injection with TTT can be an alternative treatment for CCH with exudative retinal detachment.

Optimizing irradiation volumes and evaluating the effect of dose escalation on total and fractionated doses are critical for improving outcomes in high-grade glioma (HGG).

To assess the efficacy of modified target delineation guided by multimodal magnetic resonance imaging and white matter tracts combined with moderately hypofractionated simultaneous boost intensity-modulated radiotherapy (HSIB-IMRT) in patients with newly diagnosed HGG.

This single-center, 2-arm, open-label randomized clinical trial enrolled 154 patients aged 18 to 70 years with histologically confirmed, newly diagnosed HGG at a Chinese medical center from January 1, 2018, to August 31, 2022. Follow-up was completed in June 2024.

Patients were randomized to receive modified target delineation guided by multimodal magnetic resonance imaging and white matter tracts combined with HSIB-IMRT (experimental arm) or standard IMRT per guideline recommendations (standard arm). Both arms received concurrent and adjuvant temozolomide chemotherapy.

The primary end point was progression-free survival (PFS). The secondary end point was overall survival (OS).

Among 154 enrolled patients (76 in the experimental arm and 78 in the standard arm; 85 [55.2%] male; median [range] age, 51.5 [23.0-70.0] years), the median (range) follow-up duration was 22 (4-76) months, with 96 deaths by June 2024. The median PFS was 15.5 months (95% CI, 11.7-19.3 months) in the experimental arm and 13.5 months (95% CI, 8.7-18.3 months) in the standard arm (P = .89). The median OS was 27.0 months (95% CI, 13.9-40.1 months) in the experimental arm and 21.0 months (95% CI, 18.0-24.0 months) in the standard arm (P = .24). The clinical target volume in the experimental arm (CTV1: median [range], 116.7 [20.2-370.7 cm3]; CTV2: median [range], 174.4 [34.5-463.2 cm3]) was significantly smaller than the clinical target volume in the standard arm (median [range], 225.0 [70.2-542.1 cm3]; P < .001). Recurrence rates within, outside, and multicentric to the target volume were comparable between arms. Grade 3 or 4 adverse events occurred in 4 patients (5.3%) in the experimental arm and 3 (3.8%) in the standard arm (P = .72).

In this randomized clinical trial, modified target delineation with HSIB-IMRT demonstrated comparable PFS and OS to standard IMRT in patients with newly diagnosed HGG, while significantly reducing the irradiation target volume without increasing the recurrence rates outside the target volume. These results suggest valuable insights for future research aimed at personalized, reduced volume strategies to optimize outcomes and minimize neurotoxicity in HGG.

ChiCTR.org.cn Identifier: ChiCTR1800014396.

Chemotherapy-induced alopecia (CIA) is a prominent side effect of chemotherapy, negatively impacting the patient's body image and self-confidence. Scalp cooling (SC) has emerged as a preventive option for CIA, but the success rate and adherence vary. Research shows that photobiomodulation (PBM) can improve hair growth by stimulating cell proliferation and repair processes. This trial aims to evaluate the effectiveness of PBM combined with SC in preventing CIA.

A randomized, controlled trial with 29 breast cancer patients undergoing taxane-based chemotherapy was performed at the Jessa Hospital (Belgium). Patients were randomized into the control (n = 16) or the intervention group (n = 13). Blinded researchers evaluated scalp coverage and hair thickness, while questionnaires were administered to assess scalp coverage, satisfaction, and health-related quality of life (HRQL). The trial was registered at clinicaltrials.gov (NCT05177289, 4th of January 2022).

The scalp coverage and hair thickness did not differ significantly between the two groups. Patients in the PBM group scored higher on global health (P = 0.043), physical functioning (P = 0.039), role functioning (P = 0.049), and social functioning (P = 0.038). Patients receiving a paclitaxel-based chemotherapy showed less hair loss compared to patients undergoing a docetaxel-based regimen (Ps < 0.001). No differences in SC adherence could be observed between the two groups.

The addition of PBM to SC did not increase its efficacy in preventing hair loss during chemotherapy. Patients in the PBM group did score their HRQL higher compared to the control group. Further research is required to establish the use of PBM in CIA prevention and to corroborate these findings.

Cardiac tumors are a heterogeneous group of diseases that include primary and metastatic tumors. Among primary tumors, benign tumors account for the majority, and the incidence of malignant tumors is low. In contrast, the incidence of metastatic tumors is significantly higher than that of primary tumors. The clinical features of cardiac tumors are diverse, and symptoms vary depending on the tumor type. Therefore, the diagnosis method of cardiac tumors must adopt multi-modal detection methods to ensure the accuracy of diagnosis. Treatment of cardiac tumors mainly involves surgical resection of the primary tumor to ensure complete resection. For metastatic tumors, it is crucial to consider the primary tumor when surgically resecting metastases. Depending on the characteristics of the tumor, appropriate radiation therapy or chemotherapy can improve quality of life and extend survival.

Methemoglobinemia, a rare and potentially life-threatening condition in pediatric hematology-oncology patients, requires accurate cause identification for effective treatment. We report a case of a 7-year-old boy with acute lymphoblastic leukemia who developed methemoglobinemia during chemotherapy. Initial vitamin C treatment was ineffective, requiring methylene blue. A detailed dietary history revealed the consumption of nitrate-rich vegetables and rapeseed oil, suggesting these as potential triggers. Our literature review highlights the diverse etiologies of methemoglobinemia in this patient population, emphasizing the need for heightened clinical vigilance, and careful differentiation of possible causes to guide appropriate management.