bims-netuvo 2025-07-13 papers

J Evid Based Integr Med. 2025 Jan-Dec;30:30 2515690X251356473

Ganoderma Spore Lipids Inhibit Perineural Invasion in Pancreatic Cancer by Downregulating NGF-TrkA Pathway.

Haohui Lin, Manhon Chung, Yi Yang, Li Zhang, Xiaohua Pan, Sa Cai, Yu Pan.

Perineural invasion (PNI) is an important factor leading to the recurrence of pancreatic cancer (PanCa). The NGF-TrkA pathway is related to PNI progression. Ganoderma spore lipid (GSL) is a drug with anti-cancer properties. In this study, we find out whether GSL can prevent PNI of PanCa by inhibiting NGF-TrkA pathway. In vitro, wound healing assays, transwell-based assays and three-dimensional tumor-nerve cell co-culture system showed that GSL significantly inhibited the migration and invasion capacity of PanCa cells. Inhibiting the NGF-TrkA pathway is considered an effective approach for treating PanCa. We showed that GSL effectively inhibited NGF-TrkA pathway via immunofluorescence assays and western blotting analysis. The supplement of recombinant NGF reversed the GSL inhibitory effect on the migration and invasion of PANC-1. In vivo, a sciatic nerve invasion animal model was constructed using BALB/c mice. GSL significantly suppressed tumor growth and suppressed the expression of TrkA, NGF, and vimentin and upregulated the level of the epithelial marker E-Cadherin. Moreover, GSL reduced the expression of S100 and PGP9.5. These findings suggested that GSL effectively inhibited the PNI of PanCa cells by downregulating the NGF-TrkA pathway, which may provide a new adjuvant for PanCa treatment.

Keywords: Ganoderma spore lipid; NGF–TrkA pathway; pancreatic cancer; perineural invasion

DOI: https://doi.org/10.1177/2515690X251356473

Cell Death Discov. 2025 Jul 08. 11(1): 314

Defining the cellular and molecular features of nerve-invaded cancer cells using a newly characterized experimental model.

Nickson Joseph, Sanskriti Shrestha, Ivanka Sassmannshausen, Sandra Mitzkus, Paulos Chumala, Bhadrapriya Sivakumar, Viswanath Baiju, Shahid Ahmed, Henrike Rees, George S Katselis, Anand Krishnan.

Perineural invasion (PNI) is the invasion of cancer cells into nerves. Although PNI is a risk factor for cancer recurrence and metastasis, the lack of in vitro experimental models representing natural PNI challenges basic studies and therapeutic screening. In this work, we fully characterized a dorsal root ganglia (DRG)-nerve explant model for PNI and demonstrated the characteristic cellular and molecular features of cancer cells undergoing natural PNI. Briefly, thoracic and lumbar DRGs intactly connected to nerves were co-cultured with breast and prostate cancer cells in a 3D matrix for two weeks. Time-dependent brightfield and fluorescence imaging captured the complex interactions of cancer cells, neurons, axons, and Schwann cells within nerves in the DRG-nerve preparation, demonstrating the natural invasion of cancer cells. Fundamental investigations showed that the autonomic neurotransmitters norepinephrine and acetylcholine significantly promote PNI. We also demonstrated increased survival of PNI cells in response to the treatment with the cytotoxic drug cisplatin. Additionally, we characterized the proteomics profile of PNI cells for future theranostics applications and validated the results using patient breast tumor samples. Overall, this work characterized and established a clinically relevant model for PNI and revealed the cellular crosstalk of PNI cells within nerves. The established model is suitable for fundamental studies and therapeutic screening pertaining to PNI.

DOI: https://doi.org/10.1038/s41420-025-02616-4

Clin Radiol. 2025 Jun 11. pii: S0009-9260(25)00190-4. [Epub ahead of print]88 106985

A nomogram based on magnetic resonance imaging to predict perineural invasion in mass intrahepatic cholangiocarcinoma: a two-centre, retrospective study.

D Liu, H-L Chen, F Wang, Y He, Y Yang, L Wen, Y-F Lv, D Zhang.

AIM: To evaluate the value of preoperative magnetic resonance imaging (MRI) in predicting perineural invasion (PNI) of mass intrahepatic cholangiocarcinoma (MICC) and construct a nomogram.
MATERIALS AND METHODS: This retrospective study included 228 patients with pathologically confirmed MICC who underwent preoperative MRI between January 2015 and November 2022 at two institutions. Patients were randomly divided into a training cohort (n = 160) and validation cohort (n = 68) in a 7:3 ratio based on PNI presence. Two radiologists independently analysed imaging features. Significant predictors were identified using univariate and multivariate logistic regression analyses. Predictive performance was validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A nomogram was constructed based on the optimal model.
RESULTS: Age, presence of bile duct stones, T2-weighted imaging (T2WI) signal intensity, diffusion-weighted imaging (DWI) signal intensity, intratumoural exponential apparent diffusion coefficient (eADC) values, and the tumour-to-spleen eADC ratio were significant independent predictors of PNI (all P < 0.05). The nomogram performed well in the training cohort (AUC: 0.839; 95% CI: 0.776-0.901) and validation cohort (AUC: 0.771; 95% CI: 0.658-0.883).
CONCLUSION: The T2WI signal intensity, DWI signal intensity, intratumoural eADC values, and the tumour-to-spleen eADC ratio may serve as novel noninvasive biomarkers for predicting PNI in MICC patients. The proposed nomograms can be selectively applied to enhance the accuracy of preoperative PNI predictions in patient with ICC, thereby aiding in the development of surgical strategies.

DOI: https://doi.org/10.1016/j.crad.2025.106985

Pain Manag. 2025 Jul 09. 1-3

Approach to treating cancer-induced bone pain.

Rahul Chaturvedi, Amitabh Gulati.

Keywords: Bone pain; blastic tumors; bone metastases; cancer pain; chronic pain; lytic tumors; periosteal injections; pharmacologic therapies

DOI: https://doi.org/10.1080/17581869.2025.2531738