Morphological Analysis of US Treated PANC-1 Spheroids
Source abstract
Abstract
This study investigates the impact of low-intensity continuous ultrasound (LICU) on pancreatic adenocarcinoma (PANC-1) spheroids, emphasizing morphological and volumetric transformations. PANC-1 spheroids were cultured and treated with LICU across frequencies from 1 to 5 MHz. Cell viability and mortality were analyzed through Calcein AM/PI staining, while volumetric and morphological changes were quantified across frequencies from 2 to 4 MHz using advanced imaging techniques and computational tools, including a custom Python OpenCv Library, AnaSP 3.0, a MATLAB based open source tool. Notably, a frequency of 3.5 MHz yielded optimal outcomes, also achieving a reduction in spheroid volume and mortality while minimizing disgregation, a factor linked to metastasis risk. These findings underscore LICU’s potential as an effective therapeutic strategy, balancing tumor reduction with the preservation of structural cohesion. The study establishes a methodological framework for optimizing LICU parameters, presenting a less invasive avenue for improving therapeutic outcomes in pancreatic cancer treatment.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Additive Manufacturing and 3D Printing Technologies · Elasticity and Material Modeling · Bone Tissue Engineering Materials
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Industrial Engineering (DIEF), University of Florence, Via di Santa Marta 3, 50139 Florence, Italy
Funding
Italian Ministry of University and Research
References (54)
Show source-provided references
1. Dimitri, M., Duranti, C., Aquino, S., Mazzantini, L., Iorio, J., Lulli, M., Ricci, M., Capineri, L., Arcangeli, A., and Corvi, A. (2022). Biophysical and Biomechanical Effect of Low Intensity US Treatments on Pancreatic Adenocarcinoma 3D Cultures. Appl. Sci., 12.10.3390/app12020666 ↗
2. Bazou, D., Maimon, N., Munn, L.L., and Gonzalez, I. (2017). Effects of low intensity continuous ultrasound (LICU) on mouse pancreatic tumor explants. Appl. Sci., 7.10.3390/app7121275 ↗
3. Emerging HIFU applications in cancer therapy10.3109/02656736.2014.969789 ↗
4. High intensity focused ultrasound (HIFU)
5. Escoffre, J.M., and Bouakaz, A. (2016). HIFU Tissue Ablation: Concept and Devices. Therapeutic Ultrasound, Springer.10.1007/978-3-319-22536-4 ↗
6. Biological effects of low intensity ultrasound: The mechanism involved, and its implications on therapy and on biosafety of ultrasound10.1269/jrr.45.479 ↗
7. A review of low-intensity ultrasound for cancer therapy10.1016/j.ultrasmedbio.2014.11.019 ↗
8. A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells10.1098/rsif.2015.0656 ↗
9. Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells10.1186/s13046-018-1018-6 ↗
10. Ricci, M., Barbi, E., Dimitri, M., Duranti, C., Arcangeli, A., and Corvi, A. (2024). Sonoporation, a Novel Frontier for Cancer Treatment: A Review of the Literature. Appl. Sci., 14.10.3390/app14020515 ↗
11. CO2 bubbling-based’nanobomb’system for targetedly suppressing panc-1 pancreatic tumor via low intensity ultrasound-activated inertial cavitation10.7150/thno.12691 ↗
12. Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells
13. Low-intensity low-frequency ultrasound enhances the chemosensitivity of gemcitabine-resistant ASPC-1 cells via PI3K/AKT/NF-κB pathway-mediated ABC transporters10.3892/or.2020.7671 ↗
14. González, I., Luzuriaga, J., Valdivieso, A., Candil, M., Frutos, J., López, J., Hernández, L., Rodríguez-Lorenzo, L., Yagüe, V., and Blanco, J.L. (2023). Low-intensity continuous ultrasound to inhibit cancer cell migration. Front. Cell Dev. Biol., 10.10.3389/fcell.2022.842965 ↗
15. Ultrasonic low-energy treatment: A novel approach to induce apoptosis in human leukemic cells10.1016/S0301-472X(02)00920-7 ↗
16. Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells10.1186/s12885-021-08722-7 ↗
17. Serum-free culture system for spontaneous human mesenchymal stem cell spheroid formation10.1155/2019/6041816 ↗
18. Potent antitumor activity of cepharanthine against triple-negative breast cancer spheroids compared with tetrandrine10.3892/ol.2020.12191 ↗
19. Critical role of three-dimensional tumorsphere size on experimental outcome10.2144/btn-2020-0081 ↗
20. High-throughput 3D tumor spheroid screening method for cancer drug discovery using celigo image cytometry
21. Yeon, S.E., No, D.Y., Lee, S.H., Nam, S.W., Oh, I.H., Lee, J., and Kuh, H.J. (2013). Application of concave microwells to pancreatic tumor spheroids enabling anticancer drug evaluation in a clinically relevant drug resistance model. PLoS ONE, 8.10.1371/journal.pone.0073345 ↗
22. Dinter, J., Friedrich, R.P., Yang, H., Pilarsky, C., Mangge, H., Pöttler, M., Janko, C., Alexiou, C., and Lyer, S. (2023). Mitoxantrone and mitoxantrone-loaded iron oxide nanoparticles induce cell death in human pancreatic ductal adenocarcinoma cell spheroids. Materials, 16.10.3390/ma16072906 ↗
23. Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia10.1038/bjc.2013.681 ↗
24. Exploiting the mechanical effects of ultrasound for noninvasive therapy10.1126/science.adp7206 ↗
25. Image analysis and processing of skin cell injury based on OpenCV10.1088/1742-6596/1237/3/032003 ↗
26. Meimban, R.J., Fernando, A.R., Monsura, A., Rañada, J., and Apduhan, J. (2018, January 12–16). Blood cells counting using python OpenCV. Proceedings of the 2018 14th IEEE International Conference on Signal Processing (ICSP), Piscataway, NJ, USA.10.1109/ICSP.2018.8652384 ↗
27. Tuberculosis: Image Segmentation Approach Using OpenCV
28. Fully Automated Methods for the Detection and Segmentation of Mitochondria in Microscopy Images
29. GAC3D: Improving monocular 3D object detection with ground-guide model and adaptive convolution10.7717/peerj-cs.686 ↗
30. Huang, Y., Zou, J., Badar, M., Liu, J., Shi, W., Wang, S., Guo, Q., Wang, X., Kessel, S., and Chan, L.L.Y. (2019). Longitudinal morphological and physiological monitoring of three-dimensional tumor spheroids using optical coherence tomography. J. Vis. Exp. JoVE, 144.10.3791/59020 ↗
31. Imaging growth dynamics of tumour spheroids using optical coherence tomography10.1007/s10529-006-9232-2 ↗
32. Pagnanelli, M., De Gaetano, F., Callera, A., Nappo, G., Capretti, G., Carrara, S., Ferrari, A.M.R., Cellesi, F., Costantino, M.L., and Zerbi, A. (2024). Analysis of the Mechanical Characteristics of Human Pancreas through Indentation: Preliminary In Vitro Results on Surgical Samples. Biomedicines, 12.10.3390/biomedicines12010091 ↗
33. Stiffness of pancreatic cancer cells is associated with increased invasive potential10.1039/C6IB00135A ↗
34. Bradski, G., and Kaehler, A. (2008). Learning OpenCV: Computer Vision with the OpenCV Library, O’Reilly Media, Inc.
35. Haidekker, M. (2010). Advanced Biomedical Image Analysis, John Wiley & Sons.10.1002/9780470872093 ↗
36. Altun, A.A., and Taghiyev, A. (2017, January 8–11). Advanced image processing techniques and applications for biological objects. Proceedings of the 2017 2nd IEEE International Conference on Computational Intelligence and Applications (ICCIA), Piscataway, NJ, USA.10.1109/CIAPP.2017.8167235 ↗
37. Merchant, F., and Castleman, K. (2022). Microscope Image Processing, Academic Press.
38. Sarfraz, M. (2020). Introductory Chapter: On Digital Image Processing. Digital Imaging, IntechOpen.10.5772/intechopen.92060 ↗
39. Gonzalez, R.C. (2009). Digital Image Processing, Pearson Education India.10.1117/1.3115362 ↗
40. Gedraite, E.S., and Hadad, M. (2011, January 14–16). Investigation on the effect of a Gaussian Blur in image filtering and segmentation. Proceedings of the ELMAR-2011, Zadar, Croatia.
41. Noise removal and filtering techniques used in medical images10.13005/ojcst/10.01.14 ↗
42. Unsupervised segmentation and classification of cervical cell images10.1016/j.patcog.2012.05.006 ↗
43. Mir, M.A., Qazi, F., Naseem, M., Zia, S.S., and Mubeen, T. (2022, January 14–17). Invisibility Cloak using Color Extraction and Image Segmentation with OpenCV. Proceedings of the 2022 Global Conference on Wireless and Optical Technologies (GCWOT), Malaga, Spain.10.1109/GCWOT53057.2022.9772883 ↗
44. Luo, Y., and Duraiswami, R. (2008, January 23–28). Canny edge detection on NVIDIA CUDA. Proceedings of the 2008 IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops, Anchorage, AL, USA.
45. Analysis of lane detection techniques on structured roads using OpenCV10.22214/ijraset.2020.5502 ↗
46. Piccinini, F., Peirsman, A., Stellato, M., Pyun, J.c., Tumedei, M.M., Tazzari, M., De Wever, O., Tesei, A., Martinelli, G., and Castellani, G. (2023). Deep learning-based tool for morphotypic analysis of 3D multicellular spheroids. J. Mech. Med. Biol., 23.10.1142/S0219519423400341 ↗
47. Stellato, M., Rydzyk, M.M., Pannella, M., Rossi, F., Cappadone, C., Remondini, D., Pyun, J.C., Normanno, N., Ibrahim, T., and Castellani, G. (2025). Radiomic analysis of 3D spheroids using 2D brightfield images. Biomed. Signal Process. Control., 103.10.1016/j.bspc.2024.107366 ↗
48. McKenzie, A.J., Hicks, S.R., Svec, K.V., Naughton, H., Edmunds, Z.L., and Howe, A.K. (2018). The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation. Sci. Rep., 8.10.1038/s41598-018-25589-0 ↗
49. Mechanical transmission enables EMT cancer cells to drive epithelial cancer cell migration to guide tumor spheroid disaggregation10.1007/s11427-021-2054-3 ↗
50. Disaggregation and invasion of ovarian carcinoma ascites spheroids10.1186/1479-5876-4-6 ↗
51. Quantitative cell dispersion analysis: New test to measure tumor cell aggressiveness10.1002/ijc.1380 ↗
52. Pinto, B., Henriques, A.C., Silva, P.M., and Bousbaa, H. (2020). Three-dimensional spheroids as in vitro preclinical models for cancer research. Pharmaceutics, 12.10.3390/pharmaceutics12121186 ↗
53. Cancer multicellular spheroids: Volume assessment from a single 2D projection10.1016/j.cmpb.2014.12.003 ↗
54. Mechanosensitive channel Piezo1 induces cell apoptosis in pancreatic cancer by ultrasound with microbubbles10.1016/j.isci.2022.103733 ↗