The tumour microenvironment (TME) significantly influences intercellular communication, with several secreted factors activating both tumour cells and fibroblasts. Connexin43 (Cx43), a crucial gap junction protein, exhibits a significant regulatory role in tumourigenesis; however, the underlying regulatory mechanisms in colorectal cancer (CRC) are not fully understood.

Transwell co-culture system was utilized to evaluate fibroblast-mediated effects on CRC cells. Immunohistochemical analysis was conducted on clinical specimens. Cell migration and invasion capabilities were measured using Transwell assays. Subcellular localization was assessed via immunofluorescence. Protein interactions were validated by co-immunoprecipitation.

The Wnt signalling pathway was activated in the co-culture of CRC cells and fibroblasts. Nuclear Cx43 upregulation was detected and confirmed as a pro-oncogenic factor via prognostic analysis of patient samples. Therefore, although Cx43 on the cell membrane serves as a tumour suppressor, the nuclear translocation of Cx43 has an important influence on the Wnt signalling pathway and promotes CRC progression. Nuclear translocation of Cx43 during malignant progression has a significant effect on metastasis and is regulated by secreted TGF-β. Distinct nuclear translocation patterns of Cx43 observed across CRC cell lines suggest potential regulation by S368 phosphorylation. Co-immunoprecipitation confirmed Cx43/β-catenin interaction, revealing its role in facilitating β-catenin nuclear accumulation.

We systematically identified nuclear Cx43 as a factor promoting CRC progression. These findings highlight the novel mechanism involving the nuclear translocation of Cx43 as a promoting factor in CRC progression, and enhance our understanding of the interplay between the TME and CRC progression.

Differentiated thyroid cancer (DTC) has a favorable prognosis. As indeterminate nodes are common, distinguishing recurrent and persistent DTC remains challenging. Previous studies have not specifically focused on prognosis between recurrent and persistent DTC. Thus, we aimed to compare prognosis and oncologic characteristics of two groups.

This retrospective cohort study was conducted at a single tertiary care institution, enrolling 265 patients (recurrent: 109, persistent: 156) who underwent re-operation from November 1, 1999 to August 31, 2018 due to structural diseases. Those with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncologic characteristics, patterns of lymph node (LN) metastasis, disease-free survival (DFS), and overall survival (OS) were compared between two groups. The time zero used for DFS is the time of the second operation.

Recurrent DTC exhibited higher incidence of central LN metastasis (p-value = 0.003), infield recurrence (p-value < 0.001), and distant metastasis (p-value < 0.001). In contrast, persistent DTC showed more lateral LN metastasis (p-value = 0.003) and outfield recurrence (p-value < 0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) for recurrent DTC and ipsilateral level IV (43.0%) for persistent DTC. Ten-year DFS was significantly lower for recurrent DTC (41.0%) than for persistent DTC (67.9%) (p-value < 0.001). Recurrent DTC, older age, higher total metastatic LN at the second operation (first re-operation), and R1/R2 resection at the second operation were associated with decreased DFS. OS isn't significantly different between recurrent and persistent DTC (p-value = 0.160).

: Recurrent DTC has poorer DFS than persistent DTC, although OS isn't significantly different.

This study aimed to extract radiomics features from prostate magnetic resonance imaging (MRI), evaluate their reproducibility, and determine whether machine learning (ML) models built on reproducible features can noninvasively diagnose prostate cancer (PCa).

We analyzed prostate MRI from 82 subjects (41 PCa and 41 controls) in the public PROSTATEx dataset. From T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps, 215 features per sequence were extracted (T2WI 215; ADC 215; total 430). Reproducibility within each sequence was quantified after repeated segmentation using the intraclass correlation coefficient (ICC) with a 2-way random-effects, absolute-agreement model. Only shared features with ICC≥0.75 in both T2WI and ADC were retained. Selected features were normalized and combined via early fusion into a single input vector. Redundant features were eliminated by Pearson correlation analysis (|r|>0.9).

Reproducible radiomics features (ICC≥0.75) were key contributors to model performance. Using these features, support vector machine, neural network, and logistic regression models achieved accuracies of 80%-84% and a maximum area under the receiver operating characteristic curve of 0.85 under 5-fold cross-validation. Principal component analysis yielded the most consistent results, whereas several nonlinear dimensionality reduction methods produced variable outcomes across classifiers.

Combining reproducible MRI radiomics features with dimensionality reduction and ML offers a robust noninvasive approach for PCa diagnosis. Emphasizing reproducibility enhances model performance and reliability, supporting potential clinical translation.

The objective of this systematic review was to establish an overview of changes in body composition as a result of early breast cancer treatment. Patient/material and methods: Five databases (PubMed, CINAHL, Embase, Web of Science and Cochrane Library) were used for identifying studies and papers. Selection criteria included: > 18 years, early breast cancer stage 0-III and measurement of body composition with either dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) or computed tomography (CT). Studies using only bioelectrical impedance were excluded.

A total of 734 studies were screened; 29 studies were full-text reviewed, and 10 studies were included in this systematic review, with a total of n = 1,062. Included studies were published from 2018 to 2024. This review found consistent increases in fat mass between 3.3 and 9.2% across the studies. Results for lean body mass were less consistent. Two studies examined visceral fat mass, yet both found statistically significant increases.

This systematic review identified consistent increases in total fat mass and visceral fat across the included studies, regardless of whether the treatment involved chemotherapy, endocrine therapy or a combination of both. In contrast, findings related to lean body mass were considerably less consistent. The results highlight the potential implications following breast cancer treatment and emphasise the importance of metabolic monitoring, diet and exercise to increase quality of life and prevent recurrence. This review also highlights the need for more research on the topic, as the included studies exhibit substantial heterogeneity, making it difficult to draw definitive conclusions.

Despite being a critical treatment modality, radiotherapy effectiveness is often limited by tumor resistance. Therefore, there exists a need to identify molecular targeted drugs that enhance the therapeutic response to radiation. We hypothesize that a systematic comparison of targeted radiosensitizers across two-dimensional (2D) and three-dimensional (3D) spheroid cultures will reveal context-specific differences in radiosensitivity to guide preclinical prioritization of candidate radiosensitizers.

Radiosensitizing effects of DNA-PKcs (M3814), ATR (M6620), PARP (Olaparib), and IAP (Birinapant) inhibitors using a panel of lung cancer cell lines were studied. A 3D extracellular matrix (ECM) colony formation assay for single doses of 0-6 Gy, coupled with automated colony counting, was implemented alongside standard 2D colony formation assays. Dose Enhancement Factor (DEF0.1SF) was used to compare radiosensitizing effects, and drug-radiation interactions were assessed using the Synergyfinder tool.

DNA-PKcs and ATR inhibitors induced moderate to strong dose-dependent radiosensitization (DEF0.1SF > 1.4 for at least one drug concentration) in most cell lines under both conditions (15/16 drug/cell line combinations). PARP inhibition showed similar effects in 3D and 2D (2/3 vs 3/5 combinations). Birinapant showed no relevant effect. The strongest synergy was at 2 Gy, particularly with the DNA-PK inhibitor in both culture models.

Integrating multiple culture models enhances the detection of cell line - and drug-specific radiosensitization. Although 2D and 3D cultures produced largely similar results, and 2D assays provide a practical alternative when 3D methods are not feasible, the 3D cultures reveal additional ECM-dependent responses. These results emphasize the utility of physiologically relevant platforms for robust screening and prioritization of candidate radiosensitizers.

Objective: To explore the effects of quercetin on autophagy and proliferation in HBV-positive liver cancer HCCLM3 cells based on STING signaling and its underlying mechanism. Methods: HCCLM3 cells were treated with quercetin (50 μmol/L or 100 μmol/L), designated as the 50 μmol/L group and 100 μmol/L group, respectively. The inhibitory effect of quercetin on HCCLM3 cells was detected using the CCK-8 method. A scratch assay was conducted to assess the impact of quercetin on the migration ability of HCCLM3 cells. A CCK8 and ROS kit was used to detect the effect of quercetin on the levels of reactive oxygen species in HCCLM3 cells. Western blotting was employed to measure the effect of quercetin on the expression of STING signaling and autophagy-related proteins in HCCLM3 cells. RNA interference technology was used to assess the effects of STING signaling inhibition on the expression of autophagy-related proteins and reactive oxygen species levels in HCCLM3 cells. The combined effects of STING activators and quercetin on HCCLM3 cell proliferation and autophagy were evaluated. The t-test was used to detect data differences between two groups, while ANOVA was employed for comparisons among multiple groups, followed by the SNK-q test for further pairwise comparisons. Results: Compared with the control group, quercetin (50 μmol/L and 100 μmol/L groups) significantly inhibited HCCLM3 cell survival activity in a dose-dependent manner (control group: 100%; 50 μmol/L group: 75.25%; 100 μmol/L group: 50.36%, P<0.01 ). Quercetin inhibited HCCLM3 cell migration in a dose-dependent manner (>2 h, control group: 187.16 μm; 50 μmol/L group: 145.22 μm; 100 μmol/L group: 88.21 μm, P<0.01), which significantly increased intracellular reactive oxygen species (ROS) levels in HCCLM3 cells (control group: 1.00; 50 μmol/L group: 1.565; 100 μmol/L group: 2.175, P<0.01). The phosphorylation level of STING was significantly increased (P<0.01), and the expression of autophagy-related protein microtubule-related protein 1A/1B light chain 3 (LC3) protein was significantly promoted (P<0.01). Compared with the quercetin group, the cell viability of the small interfering-STING+quercetin group was increased (quercetin group: 56.3%; small interfering-STING+quercetin group: 85.7%, P<0.05), while the expression of autophagy-related protein LC3 was decreased. Compared with the quercetin group, the cell viability of the quercetin+STING activator group was further decreased (quercetin group: 56.7%; quercetin+STING activator group: 35.4%, P<0.01), and the expression levels of STING and autophagy protein LC3 were significantly increased (P<0.05). Conclusions: STING signaling-regulated cell autophagy mediates the inhibitory effect of quercetin on the proliferation of HCCLM3 cells, and this effect is enhanced after administration of the STING agonist.

Hepatocellular carcinoma (hereinafter referred to as liver cancer) is the main indication for liver transplantation in China, but postoperative tumor recurrence and metastasis severely restrict the efficacy of liver transplantation. There exist significant differences between the traditional liver cancer research models due to the long-term immunosuppressive state of transplant recipients and the complex mechanism of tumor recurrence and metastasis, posing enormous challenges to existing theoretical system. Therefore, it is crucial to innovate the scientific research pattern and liver transplantation clinical management model for liver cancer. Herein, the author's team has innovatively proposed a 'Tumor-Donor Liver-Recipient' integrated research horizon for liver transplantation in liver cancer based on prior clinical practice and scientific exploration, with the aim to expand new concepts in basic research, explore new strategies for precise clinical intervention, and establish a refined recipient management system. This paper systematically elaborates on the research general situation and cutting-edge perspectives under the "tumor-donor liver-recipient" so as to classify HCC liver transplantation patients, pre-transplant downstaging therapy, scientific evaluation and application of donor livers, innovations in transplant surgical techniques, and individualized postoperative management.

Objective: To investigate the clinical values of fluorescent PCR-capillary electrophoresis (PCR/CE) for detecting somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) in endometrial carcinomas (EC), as compared with Sanger sequencing. Methods: A total of 280 EC cases diagnosed at the Department of Pathology at Peking University Third Hospital, Beijing, China from December 2022 to December 2023 were collected. Ten cases, which had previously been confirmed to harbor POLE pathogenic mutations through next-generation sequencing (NGS), were excluded. Subsequently, parallel sequencing using both PCR/CE and Sanger sequencing methods was conducted on the remaining 270 EC samples without prior POLE testing, aiming to examine 11 known pathogenic mutation-sites located within exons 9, 11, 13, and 14 of the POLE gene. NGS was then carried out on the EC cases in which the PCR/CE and/or Sanger sequencing results indicated the presence of POLE-exo*. Results: Among the 270 EC samples, POLE-exo* was detected in 4 cases (4/270, 1.5%) using Sanger sequencing. In contrast, the PCR/CE identified POLE-exo* in 12 cases (12/270, 4.4%). It was noteworthy that all cases in which POLE-exo* was detected through Sanger sequencing were also successfully identified using PCR/CE (4/4, with a detection rate of 100%). These results were further verified by NGS. The PCR/CE also uncovered an additional 8 cases (8/266, 3.0%) of POLE-exo* in the 266 samples that were negative for POLE mutations per Sanger sequencing. Of these 8 cases, 4 were validated using NGS, exhibiting variant allele frequency (VAF) below 10%, but tumor mutation burdens exceeding 10 mutations per megabase. However, due to small tumor sizes, NGS verification could not be performed on the remaining 4 PCR/CE-positive but Sanger-negative cases. Conclusion: The PCR/CE exhibits better sensitivity and detection capabilities than the Sanger sequencing in identifying POLE-exo* in EC samples, particularly in detecting low VAF.

Objective: To investigate the clinicopathological characteristics of ossifying fibromyxoid tumor (OFMT) with rare fusion subtypes. Methods: Three cases of OFMT with rare fusion subtypes, diagnosed and consulted in the Zhejiang Hospital, Zhejiang Provincial People's Hospital, Hangzhou, China and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China from January 2016 to December 2024 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted RNA sequencing were performed to analyze the immunohistochemical and molecular genetic characteristics of these OFMT. Literature review was also conducted. Results: All three patients were male, with ages of 50, 74, and 58 years, respectively. The tumors were located in the left foot, left thigh, and left lumbar region, respectively, and all presented as slowly growing, painless masses in the skin or subcutaneous tissue. Grossly, the tumors measured 3.5 cm, 6.3 cm, and 5.0 cm in maximum diameter, respectively, with a grayish-white to grayish-yellow, solid, lobulated cut surface. One case exhibited a noticeable myxoid texture. Microscopically, one tumor was located in the superficial dermis, while the other two were in the subcutaneous tissue. The tumors were well-demarcated and showed a lobulated or multinodular growth pattern. None of the cases had a complete surrounding bony shell (only one case had very focal ossification). The tumor cells were monomorphic, short spindle-shaped, oval to epithelioid, and arranged in solid sheets, trabeculae, and small nests within a variably fibromyxoid stroma. Case 1 exhibited abundant pseudorosette-like structures formed by short spindle cells surrounding acellular fibrous stroma. Case 2 showed focal transition of epithelioid tumor cells into fasciculately arranged spindle cells, with extensive stromal hyalinization. Case 3 had a predominantly myxoid stroma with a rich network of thin-walled blood vessels. The tumor cells exhibited mild nuclear atypia with 1-3 mitotic figures per 50 high-power fields. All three cases showed diffuse and strong expression of CD10. Two of the three cases showed nuclear expression of TFE3, while one case showed diffuse and strong expression of desmin and S-100. Targeted RNA sequencing revealed PHF1 (ex12)::TFE3 (ex7) fusion in two cases and MEAF6 (ex5)::PHF1 (5'UTR) fusion in one case, which were further confirmed by FISH study. All three patients underwent tumor resection. Two showed no recurrence during follow-up periods of 98 months and 15 months, respectively, while one experienced local recurrence at 12 months postoperatively. Conclusions: OFMT with rare fusion subtypes often exhibits atypical histological and immunophenotypic features, and lacks a characteristic bony shell. Incorporating TFE3 into the diagnostic IHC panel greatly aids in screening for the cases with rare PHF1::TFE3 fusions. Familiarity with the histological and immunophenotypic characteristics, and differential diagnostic points of these rare OFMT subtypes, is essential for judicious use of molecular genetic tools in achieving a definitive diagnosis.