Cancer Research and Treatment

Original Articles

Gynecologic cancer

Application of Machine Learning Algorithms for Risk Stratification and Efficacy Evaluation in Cervical Cancer Screening among the ASCUS/LSIL Population: Evidence from the Korean HPV Cohort Study: Heekyoung Song, Hong Yeon Lee, Shin Ah Oh, Jaehyun Seong, Soo Young Hur, Youn Jin Choi; Cancer Res Treat. 2025;57(2):547-557. Published online September 6, 2024; DOI: https://doi.org/10.4143/crt.2024.465

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Purpose
We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods
Between 2010 and 2021, we monitored 1,273 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types (a) 16 and 18; (b) 31, 33, and 45; and (c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates.
Results
Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p < 0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p < 0.001), followed by Hr1-b (9.26, p < 0.001) and Hr1-c (7.21, p < 0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination.
Conclusion
In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

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Geneticsbiologiesingle cell and expression analysis for erectile dysfunction and cervical cancer targets
Tengfei Zhao, Yangyang Li, Huixue Liu, Chongxin Tong
Discover Oncology.2024;[Epub] CrossRef

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Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer: Mi-Ryung Han, Sug Hyung Lee, Jung Yoon Park, Hyosun Hong, Jung Yoon Ho, Soo Young Hur, Youn Jin Choi; Cancer Res Treat. 2020;52(3):779-788. Published online February 28, 2020; DOI: https://doi.org/10.4143/crt.2019.700

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients.
Materials and Methods
Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients.
Results
Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC.
Conclusion
Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

Citations

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Circulating Tumour DNA for Ovarian Cancer Diagnosis and Treatment Monitoring: What Perspectives for Clinical Use?
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ctDNA as an Objective Marker for Postoperative Residual Disease in Primary Advanced High-Grade Serous Ovarian Cancer
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Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling in the ES-2 Ovarian Carcinoma Cell Line, Influencing Cell Proliferation, Quiescence, and Chemoresistance in a Cell-of-Origin-Specific Manner
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Metabolites.2025; 15(4): 244. CrossRef
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Biomedical Journal.2025; : 100851. CrossRef
Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence
Giovanni Marchi, Anna Rajavuori, Mai T.N. Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
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Elena Trevisi, Cristiana Sessa, Ilaria Colombo
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Cell‐free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer
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An Open-Label, Randomized, Parallel, Phase II Trial to Evaluate the Efficacy and Safety of a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel as First-Line Treatment for Ovarian Cancer: A Korean Gynecologic Oncology Group Study (KGOG-3021): Shin-Wha Lee, Yong-Man Kim, Chi Heum Cho, Young Tae Kim, Seok Mo Kim, Soo Young Hur, Jae-Hoon Kim, Byoung-Gie Kim, Seung-Cheol Kim, Hee-Sug Ryu, Soon Beom Kang; Cancer Res Treat. 2018;50(1):195-203. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2016.376

Abstract PDF PubReader ePub

Purpose
Genexol-PM is a biodegradable cremophor EL–free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment.
Materials and Methods
In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR).
Results
Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m² Genexol-PM or 174.24±3.81 mg/m² Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable.
Conclusion
Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

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A Clinicopathological Review of Pulmonary Metastasis from Uterine Cervical Cancer: Eun Young Ki, Keun Ho Lee, Jong Sup Park, Soo Young Hur; Cancer Res Treat. 2016;48(1):266-272. Published online February 23, 2015; DOI: https://doi.org/10.4143/crt.2014.206

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the clinicopathological features of pulmonary metastasis from cervical cancer. Materials and Methods We reviewed the medical records of 56 patients with cervical cancer who developed pulmonary metastasis after radical hysterectomy, postoperative concurrent chemoradiation or systemic chemotherapy between January 1990 and March 2014.
Results
Fifty-six patients were diagnosed with pulmonary metastasis from cervical cancer. The prevalence of pulmonary metastasis was 3.6%. The mean event-free duration was 12 months. Twelve patients underwent surgical removal of metastatic lesions. The overall survival (OS) of patients with ≤ 3 metastatic lung lesions was 40.7 months, longer than those with > 4 lesions (25 months, p=0.034). The OS of patients who underwent surgical resection was 53.8 months, longer than that of those who did not (p=0.006). In addition, the OS of patients with adjuvant platinum-based chemotherapy was 32.6 months (p=0.027). Conclusion In this study, we found that the number of metastatic nodules, surgical resection, and postoperative platinum-based chemotherapy can influence clinical outcome. Further studies on prognostic factors and successful treatment modalities are warranted.

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New Approaches to Functional Process Discovery in HPV 16-Associated Cervical Cancer Cells by Gene Ontology: Yong Wan Kim, Min Je Suh, Jin Sik Bae, Su Mi Bae, Joo Hee Yoon, Soo Young Hur, Jae Hoon Kim, Duck Young Ro, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Woong Shick Ahn; Cancer Res Treat. 2003;35(4):304-313. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.304

Abstract PDF

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BAG3 down-modulation sensitizes HPV18+ HeLa cells to PEITC-induced apoptosis and restores p53
Roberta Cotugno, Anna Basile, Elena Romano, Dario Gallotta, Maria Antonietta Belisario
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Expression Profiling of the Cellular Processes in Uterine Leiomyomas: Omic Approaches and IGF-2 Association with Leiomyosarcomas
Su Mi Bae, Yong-Wan Kim, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Woong Shick Ahn
Cancer Research and Treatment.2004; 36(1): 31. CrossRef

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Changes of Telomerase Activity by Protein Kinase C Modulators in Human Ovarian Cancer Cell Lines: Soo Young Hur, Joon Mo Lee, Sung Eun Namkoong, Jin Woo Kim; J Korean Cancer Assoc. 2000;32(4):724-733.

Abstract PDF: PURPOSE
This study was designed to find out whether protein kinase C (PKC) may affect telomerase activity in human ovarian cancers.
MATERIALS AND METHODS
To determine whether PKC modulators influence PKC activities, NIH: OVCAR-3 and CUMO-2, cells were treated with PKC inhibitors, G 6976 and bisindolyl maleimide I, and PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Telomerase acti vity was determined by telomeric repeat amplification protocol (TRAP). Analysis of the expres sion of each telomerase subunits, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT), was performed by RT-PCR. We also examined the alternative splicing of hTERT.
RESULTS
G 6976 and bisindolylmaleimide I inhibited PKC activity. Telomerase activities appeared to be affected in a time-dependent manner by these two PKC inhibitors. PKC activities were increased in parallel with telomerase activity by TPA at the low dose (10 nM), but their activities were down-regulated at the high dose (1 micrometer). RT-PCR demonstrated the presence of hTR and hTERT mRNA before and after the treatment of PKC modulators, respectively, and showed the presence of one alternatively spliced transcript and full-length hTERT transcripts.
CONCLUSION
These results showed that telomerase activity was affected by PKC and suggested PKC modulation may serve as an useful tool in the regulation of telomerase activity.

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Development of a New Nonoclonal Antibody CC5 Using a Cervical Carcinoma Cell-line Derived From Korean Woman: Jin Woo Kim, Chun Ok Seo, Eun Young Cho, Heung Kee Kim, Sa Jin Kim, Soo Young Hur, Young Wook Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1999;31(3):562-574.

Abstract PDF: PURPOSE
Cancer of the uterine cervix remains the leading cause of cancer death in Korean women. Conventional examinations still have limitations with regards to sensitivity and specificity in diagnosis and to monitoring of the disease. Thus, an additional specific tumor marker is needed for early detection of recunence of uterine cervical carcinoma and for estimation of prognosis.
MATERIALS AND METHODS
Monoclonal antibodies against human cervical carcinoma were generated using hybridoma technology. These tnurine monoclonal antibodies were produced by fusion of spleen cells obtained from mice immunized with CUMC-6, a human cell line of squamous cell carcinoma derived from uterine cervix, and P3-X63-Ag8 mouse myeloma cells.
RESULTS
We obtained 415 hybridomas secreting specific monoclonal antibodies to cervical carcinoma antigen continuously. Among them, one hybridoma designated CCS that was highly reactive with cervical carcinoma was selected and examined on. the staining pattern and the reactivity with antigenic detenninants of cervical carcinoma. Immunohistochemical staining revealed that CCS monoclonal antibody reacted with all of the seven cervical carcinoma tissues, but also reacted with one of the ten (10%) normal cervical tissues. Westem blot analysis showed that CC5 monoclonal antibody detected single 19.5-kDa protein band in cervical cancer patient's sera. The detection rate was 88% (7/8). However, the antibody did not show any reactivity to 15 sera of normal healthy women tested. Sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of CCS monoclonal antibody immunoprecipitates of extracts of L-[S] methionine-labeled human cer vical carcinoma cells showed a major band in apparent molecular weight of 51,000 daltons. The isotype and subclass of CC5 monoclonal antibody was IgG2b in hemagglutination assay.
CONCLUSIONS
We have developed a new monoclonal antibody, CC5, against squamous cell carcinoma of the human uterine cervix. Further investigation is needed to establish this monoclonal antibody as an immunodiagnostic devise for cervical cancer.

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