Hubei Cancer Hospital

Aprepitant, a neurokinin-1 receptor antagonist approved by the US FDA for chemotherapy- and postoperative-induced nausea and vomiting, has limited real-world safety data; we therefore interrogated the FDA Adverse Event Reporting System from Q1 2004 to Q3 2023 to systematically characterize aprepitant-associated adverse drug events. After extracting 8271 reports on 3033 patients, we applied a combined signal detection framework – reporting odds ratio, proportional reporting ratio and the Bayesian confidence propagation neural network with multi-item gamma Poisson shrinker – and analyzed demographics, reporter profiles and temporal trends. Women represented 54.10% of cases, the 45 to 65-year age group 27.86%, and healthcare professionals filed 65.64% of reports; the United States, France, Japan, the United Kingdom, and China contributed most cases, peaking during 2013 to 2019. While labeled toxicities were confirmed, novel high-strength signals emerged, including joint deposition, oral mucosal roughening, encephalopathy, dysplasia, febrile myelodysplasia, small cell lung cancer and tonic-clonic movements, whereas dyspnea and nausea remained the 2 most frequently reported events. These findings corroborate known risks and unveil previously under-recognized aprepitant related adverse reactions, providing actionable safety guidance for clinicians and suggesting that the strong joint deposition signal warrants prospective investigation of aprepitant in arthritic disorders.

The cachexia index (CXI) demonstrates potential as both a diagnostic tool for cachexia and a prognostic tool for survival in cancer. However, CXI's predictive value has not been verified in cervical cancer. The purpose of this study is to investigate the prognostic value of the CXI in patients with cervical cancer treated with radiotherapy. We retrospectively screened patients diagnosed with cervical cancer who underwent radiotherapy in a single institution between September 2013 to September 2015. The CXI was calculated as the skeletal mass index (SMI) × albumin/neutrophil-to-lymphocyte ratio. SMI was measured by computed tomography using the muscles of the third lumbar vertebra. Survival times were evaluated using the Kaplan-Meier method and Cox proportional hazards regression. A nomogram for predicting survival was developed. A total of 81 patients with cervical cancer were included. The cutoff value of the CXI was set at 59.7 using receiver operating characteristic (ROC) analyses. According to this cutoff value, 47 patients were assigned to the high-CXI group, and 34 were assigned to the low-CXI group. The Cox regression analysis showed that a low CXI was associated with decreased overall survival (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 1.24-8.00; P = 0.016). Patients in the low-CXI group also had shorter progression-free survival than those in the high-CXI group, but the difference was of borderline significance (HR: 2.26; 95% CI: 1.00-5.11; P = 0.05). The pretreatment CXI is an independent prognostic factor in patients with FIGO II-III cervical cancer treated with radiotherapy.

Lung cancer (LC) causes large amount of cancer death worldwide. As the most common and aggressive type of LC, the molecular mechanisms in LUAD (Lung Adenocarcinoma) remain unclear. In order to find novel potential molecular targets for improving the prognosis of LUAD, we obtained gene information of LUAD patients from The Cancer Genome Atlas (TCGA) and identified hub genes through weighted gene co-expression network analysis (WGCNA). We selected the top 25% of total 5945 differently expressed genes (DEGs) and established 16 modules. The purple module was highly associated with tumor stage and chosen as key module. Further analysis revealed that the level of 6 hub genes (TRIM31, DKK1, FAM83A, RHOV, S100P and TSKU) were negatively relevant to survival rate but positively correlated with advanced tumor stage. Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative PCR (RT-qPCR) verified the high expression of TRIM31 in LUAD. Loss-of-function assays indicated TRIM31 accelerated viability, proliferation and metastasis of LUAD cells. According to the UbiBrowser website, TRIM31, as an E3 ubiquitin ligase, may be involved in the ubiquitination of P53, an important tumor suppressor. Co-immunoprecipitation verified the interaction between TRIM31 and P53. More importantly, the degradation rate of P53 was slowed when TRIM31 was knockdown. Further immunoblot assays revealed that TRIM31 promoted the ubiquitination and degradation of P53. P53 could inhibit the expression of SLC7A11 and was regarded as an important regulator of ferroptosis. Ferroptosis analysis showed that TRIM31 knockdown decreased cell viability and GSH, but increased ROS, MDA and iron, which could reverse by knockdown of P53. Above results displayed that TRIM31 effected ferroptosis level via P53. In addition, website prediction showed that BATF was a transcription factor of TRIM31, and experiments confirmed that BATF could indeed promote the transcription of TRIM31. Taken together, the data demonstrated that TRIM31 promoted LUAD progression by inhibiting ferroptosis via the TRIM31/P53/SLC7A11 axis.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign tumor with varied histological morphology. The rarity and morphological heterogeneity of PSP may pose diagnostic challenges for pathologists. In this study, we retrospectively reviewed the clinicopathological features of 36 PSPs, and explored the diagnostic value of Ki-67 MIB-1 in PSPs. Among these PSPs, there was a significant female predominance. Microscopically, the tumors were all composed of a dual-cell population, and had a combination of at least two of the four growth patterns, i.e. papillary, sclerotic, solid and hemorrhagic. Immunohistochemically, the surface cells were TTF1 (+)/CK7 (+), while the stromal cells were TTF1 (+)/CK7 (-). Ki-67 MIB-1 highlighted the immunostaining of cell membrane and cytoplasmic in tumor cells when performed at room temperature (20°C-25°C) using the Benchmark ULTRA system. Such a staining pattern of MIB-1 was significantly higher in PSPs than that in NSCLCs (p < 0.001). This is helpful for the differential diagnosis, especially for core biopsy specimens which are often limited for sampling. Basing on the careful morphological observation and TTF-1/CK7 immunostaining could diagnose most PSPs, while a unique cell membrane and cytoplasmic staining of MIB-1 performed at room temperature could be a useful adjunct to the accurate diagnosis of PSP.

The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group. The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

Abstract Cervical cancer remains a significant threat to women's health globally, especially in low- and middle-income countries where cytology serves as the primary screening modality. Conventional cytology screening relies on pathologists reviewing slides, which is time-consuming and limited by inter-observer consistency. While AI-driven deep learning has advanced automated cervical cytology analysis, existing methods typically depend on abundant annotations and lack general-purpose capabilities across tasks and datasets. Faced with such challenges, we introduce CervixFM, the first general foundation model for cervical cytology image analysis. We curated a massive pretraining dataset using 18,375 whole-slide images collected from 38 batches across four medical centers, resulting in over 64 million tiles. Leveraging the large-scale data, CervixFM learns feature primitives of cervical cells via a self-supervised framework. Our model, a large vision transformer, has been systematically evaluated on five types of common analysis tasks, including slide-level classification, patch-level classification, retrieval, segmentation, and detection, and has achieved improved performance surpassing current state-of-the-art models in 34 cervical abnormality analysis. Our evaluation covers nearly all publicly available datasets in the field and involves comparisons with pretrained encoders from natural image domain and histopathology foundation models, ensuring the comprehensiveness of evaluation results. Furthermore, we investigated the label efficiency of CervixFM under low-resource supervision and assessed its cross-domain retrieval capability on six non-cervical cytology datasets. Experimental results demonstrate that CervixFM effectively captures robust representations of cervical cells, offering a new paradigm to mitigate the long-standing bottlenecks of high annotation costs and poor cross-task and cross-dataset generalizability.

Ascites represents an extremely unique liquid immunosuppressive microenvironment of epithelial ovarian cancer (EOC), and it contains a substantial quantity of macrophages; however, these macrophages fail to exhibit effective anti-tumor activity. Peritoneal mesothelial cells (PMCs) constitute a critical component of ascites. Whether PMCs can modulate macrophages function through some mechanisms, thereby influencing the tumor immune microenvironment, remains to be elucidated. Co-culture models of EOC-educated PMCs (EOC-PMCs) and macrophages in human and mouse were respectively constructed, and verified the differences of polarization markers, cytokines, and metabolic levels in macrophages after co-culture. Transcriptional sequencing experiments confirmed that polypeptide N-acetylgalactosaminyltransferase 15 (Galnt15) was highly expressed in macrophages after co-culture. Nuclear-cytoplasmic protein separation and immunofluorescence (IF) were used to confirm that the nuclear entry of peroxisome proliferator-activated receptor γ (PPARγ) increased and the polarization of macrophages was enhanced when Galnt15 was overexpressed. In vitro experiments, the overexpression and knockdown of Galnt15 were achieved using plasmids and siRNAs. Immunoprecipitation (IP) experiments verified that high expression of Galnt15 mediated the O-glycosylation of PPARγ, thereby affecting the nuclear entry of PPARγ. Site mutation and fusion protein detection were employed to explore the functional site of Galnt15-mediated O-glycosylation of the PPARγ protein. And an EOC model in situ was established on the ovary of C57BL/6J, and it was confirmed in vivo and in vitro that macrophages treated with EOC-PMCs played a pro-cancer role. Tissue microarrays confirmed that the expression of Galnt15 and PPARγ was related to patient prognosis. EOC-PMCs led to high expression of Galnt15 in macrophages. Galnt15 promoted O-glycosylation and nuclear translocation of PPARγ, subsequently enhancing fatty acid oxidation (FAO) metabolism, and inducing macrophages polarization and secretion of pro-tumor cytokines. Animal experiments showed that EOC-PMCs increased the FAO metabolism level of macrophages to promote tumor development. Tissue microarray also confirmed that there was a positive correlation between the expression of Galnt15 and PPARγ, and patients with high expression of Galnt15/PPARγ had a poorer prognosis. EOC-PMCs promote macrophages polarization through the Galnt15/PPARγ pathway, which is conducive to the formation of an immunosuppressive microenvironment in ascites and ultimately facilitates the progression of ovarian cancer.