Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples: Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee; Cancer Res Treat. 2022;54(3):737-743. Published online September 24, 2021; DOI: https://doi.org/10.4143/crt.2021.773

Abstract PDF Supplementary Material PubReader ePub

Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

Citations to this article as recorded by

Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy
Shuai Wang, Yongsen Wang, Xuan Wu, Li Yang, Xiaoju Zhang
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Clinicopathologic features of histologic transformation in lung adenocarcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitors
Halim Song, Deokhoon Kim, Se Jin Jang, Hee Sang Hwang, Joon Seon Song
Annals of Diagnostic Pathology.2025; 77: 152478. CrossRef
Whole Exome Sequencing Study Identifies Distinct Characteristics of Transformed Small Cell Lung Cancer With EGFR Mutation Compared to De Novo Small Cell and Primary Non‐Small Cell Lung Cancers
Jinjing Tan, Dan Zhao, Qunhui Wang, Yanjing Peng, Jie Li, Xi Li, Nanying Che, Ying Hu, Hua Zheng
Cancer Medicine.2025;[Epub] CrossRef
Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: A proof‐of‐concept study
Mohammadali Ahmadipour, Jorge Castilo Prado, Benyamin Hakak‐Zargar, Malik Quasir Mahmood, Ian M. Rogers
Biotechnology and Bioengineering.2024; 121(10): 3020. CrossRef
Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
Cancer Research Communications.2024; 4(7): 1738. CrossRef
Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases
Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
Journal of Clinical Medicine.2023; 12(4): 1411. CrossRef
Gene‐level dissection of chromosome 3q locus amplification in squamous cell carcinoma of the lung using the nCounter assay
Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
Thoracic Cancer.2023; 14(26): 2635. CrossRef
Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
Cancer Research and Treatment.2023; 55(4): 1181. CrossRef
Challenges and Opportunities for Immunoprofiling Using a Spatial High-Plex Technology: The NanoString GeoMx® Digital Spatial Profiler
Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
Frontiers in Oncology.2022;[Epub] CrossRef

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Uptake of Ga-67 by Cultured Cells: Transferrin-dependent and Transferrin-independent Mechanisms: Myung Hee Sohn, Seok Tae Lim, Jae Yong Kwak, Chang Yeol Yim; J Korean Cancer Assoc. 2000;32(4):742-749.

Abstract PDF: PURPOSE
We determined whether the uptake of Ga-67 by cultured cells occur by both transferrin (Tf)-dependent and independent mechanisms and the mechanism and magnitude of its uptake may vary as the degree of expression of the transformed phenotype.
MATERIALS AND METHODS
Uptake of Ga-67 between the tansformed and untransformed cells was compared. Cells were incubated with Ga-67 in either the presence or absence of Tf and with complete medium containing Ga-67 after preincubating with anti-Tf receptor antibodies at 37oC in 8% CO2. Monolayers of cells were washed and trypsinized. Radioactivity and protein content of the samples were determined.
RESULTS
Uptake of Ga-67 by cultured cells occurred both in Tf-bound and ionic form and was increased with radioactivity and time. The magnitude for the uptake of Tf-bound form was approximately 3 and 6-fold greater than ionic form. In the presence of Tf, uptake of Ga-67 was 2-fold greater in the transformed cells. Conversely, In the absence of Tf, it was 1.5-fold greater in the untransformed cells. Regardless of blocking the Tf receptor by anti-Tf receptor antibodies, a significant amount of intracellular Ga-67 uptake was found.
CONCLUSION
Dual mechanisms exist for the uptake of Ga-67 by cultured cells. The primary important one was the Tf-dependent system. Tf-dependent and independent mechanisms and the magnitude operated oppositely in the transformed cells when compared to their untransformed counterpart.

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Morphological Transformation Region II (mtrII) of Human Cytomegalovirus: Yeon Myung Shin, Soo Sang Sohn, Joong Shin Kang, Sung Ik Chang, In Hwan Lee; J Korean Cancer Assoc. 1997;29(3):495-503.

Abstract PDF: PURPOSE
Human herpesviruses have been associated with the etiology of several human cancers. The role of these viruses in carcinogenesis has not yet been clarified. This study focused on identifying and characterizing the transforming potential of cloned DNA fragments from human cytomegalovirus (HCMV).
MATERIALS AND METHODS
Multiple DNA fragments of HCMV were applied to cells for transformation. Morphological transforming region II (mtrII) of HCMV strain Towne has been identified to a 3.0kb XbaI-BamHI DNA fragment which was retained in transformed cells. The transforming activity was induced by a 980 bp BaII-Xho I subfragment (pBS980) containing both promoter/ regulatory elements as well as three open reading frames (ORFs), i.e., 79ORF, 83ORF, and 34ORF. The ORFs have been evaluated for transforming potential in NIH3T3 cells.
RESULTS
MtrII (pBS980) has BglII restriction enzyme site which divides into two subfragments, pBS440 and pBS540, the latter has whole 83ORF, 34ORF, and fragment of 79ORF, the former has only fragment of 79ORF. Among three ORFs, 83ORF and 34ORF were not functional in transformation, because in pBS540 these ORFs were not truncated.
CONCLUSION
The 79ORF (79-aa transforming peptide) has allowed a better approach to determine the role of HCMV in human carcinogenesis.

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