• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1471-1477
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• 2015

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3267-3272
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• 2015

Purpose: To retrospective assess the potential predictors for relapse and create an effective clinical mode for surveillance after orchidectomy in clinical stage I non-seminomatous germ cell testicular tumors (CSI-NSGCTs). Materials and Methods: We analyzed data for CSI-NSGCTs patients with non-lymphatic vascular invasion, %ECa < 50% (percentage of embryonal carcinoma < 50%), and negative or declining tumor markers to their half-life following orchidectomy (defined as low-risk patients); these patients were recruited from four Chinese centers between January 1999 and October 2013. Patients were divided into active surveillance group and retroperitoneal lymph node dissection (RPLND) group according to different therapeutic methods after radical orchidectomy was performed. The disease-free survival rates (DFSR) and overall survival rates (OSR) of the two groups were compared by Kaplan-Meier analysis. Results: A total of 121 patients with CSI-NSGCT were collected from four centers, and 81 low-risk patients, including 54 with active surveillance and 27 with RPLND, were enrolled at last. The median follow-up duration was 66.2 (range 6-164) months in the RPLND group and 65.9 (range 8-179) months in the surveillance group. OSR was 100% in active surveillance and RPLND groups, and DFSR was 89.8% and 87.0%, respectively. No significant difference was observed between these two groups ($X_2=0.108$, P=0.743). No significant difference was observed between the patients with a low percentage of embryonal carcinoma (<50%) and those without embryonal carcinoma (87.0% and 91.9%, $X_2=0.154$, P=0.645). No treatment-related complications were observed in the active surveillance group whereas minor and major complications were observed in 13.0% and 26.1% of the RPLND group, respectively. Conclusions: Active surveillance resulted in similar DFSR and OSR compared with RPLND in our trial. Patients with low-risk CSI-NSGCTs could benefit from risk-adapted surveillance after these patients were subjected to radical orchidectomy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.2
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• pp.101-106
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• 2006

Purpose: The purpose of this study is to evaluate the value of proliferation factors, Ki67 and PCNA, as prognostic markers predicting the survival and neck metastasis in patients with oral cancer. Methods: 101 patients with HNSCCs, were followed retrospectively for a median period of 60 months(from 16 to 82 months). All tumors were resected surgically and examined by conventional light microscopy, immunohistochemistry. The age, sex, tumor location, clinical stage(size), metastasis, proliferative activity index(assessed by proliferating cell nuclear antigen(PCNA) and Ki67 immunoreactivity) were considered as potential prognostic factors and were correlated with patient survival. Results: Ki67 staining results ranged from 5% to 80% of tumor cell nuclei, with a median of 25%. PCNA staining results ranged from 1% to 90% with a median of 50%. With a cut-off point of 25%, patients with lower Ki67 scores showed survival advantages over those with higher Ki67 scores (p=0.0089). With cut-off point of 50%, patients with lower PCNA scores showed survival advantages over those with higher PCNA scores (p=0.0104). Pathologically neck node positive patients(n=27) showed higher PCNA expression(p=0.02) than pathologically negative neck node patients(n=39). Conclusions: The lower expressions of Ki67 and PCNA were associated with favorable prognosis such as higher survival rate and lower neck node metastasis.

• Investigative Magnetic Resonance Imaging
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• v.19 no.4
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• pp.218-223
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• 2015

Purpose: To investigate whether volumetric analysis based on T2WI and contrast-enhanced (CE) T1WI can distinguish between isocitrate dehydrogenase-1 mutation-positive ($IDH1^P$) and -negative ($IDH1^N$) glioblastomas (GBMs). Materials and Methods: We retrospectively enrolled 109 patients with histopathologically proven GBMs after surgery or stereotactic biopsy and preoperative MR imaging. We measured the whole-tumor volume in each patient using a semiautomatic segmentation method based on both T2WI and CE T1WI. We compared the tumor volumes between $IDH1^P$ (n = 12) and $IDH1^N$ (n = 97) GBMs using an unpaired t-test. In addition, we performed receiver operating characteristic (ROC) analysis for the differentiation of $IDH1^P$ and $IDH1^N$ GBMs using the tumor volumes based on T2WI and CE T1WI. Results: The mean tumor volume based on T2WI was larger for $IDH1^P$ GBMs than $IDH1^N$ GBMs ($108.8{\pm}68.1$ and $59.3{\pm}37.3mm^3$, respectively, P = 0.0002). In addition, $IDH1^P$ GBMs had a larger tumor volume on CE T1WI than did $IDH1^N$ tumors ($49.00{\pm}40.14$ and $22.53{\pm}17.51mm^3$, respectively, P < 0.0001). ROC analysis revealed that the tumor volume based on T2WI could distinguish $IDH1^P$ from $IDH1^N$ with a cutoff value of 90.25 (P < 0.05): 7 of 12 $IDH1^P$ (58.3%) and 79 of 97 $IDH1^N$ (81.4%). Conclusion: Volumetric analysis of T2WI and CE T1WI could enable $IDH1^P$ GBMs to be distinguished from $IDH1^N$ GBMs. We assumed that secondary GBMs with $IDH1^P$ underwent stepwise progression and were more infiltrative than those with $IDH1^N$, which might have resulted in the differences in tumor volume.

• Journal of Gastric Cancer
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• v.12 no.2
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• pp.113-119
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• 2012

Purpose: The aim of this study is to compare the characteristics of tumor and prognosis, depending on the status of resection margin involvement, on the frozen section diagnosis in gastric cancer. Materials and Methods: This study was conducted retrospectively, in 83 margin-positive patients on the frozen section diagnosis, who underwent gastrectomy from July 1995 to September 2006. The control group was selected by matching the age, gender, TNM stage and status of adjuvant chemoradiotherapy, among those who had shown clear resection margins. The characteristics of tumor and patient survival are investigated, and they were analyzed between the two groups. Results: The tumor size was significantly larger in the study group than that of the control group (P=0.037). There was significant difference between the two groups in location of the tumors (P=0.003). Multivariate analysis indicated that only the location and Lauren's classification are independent factors, which affected the resection margin involvement. Median survival was $41.0{\pm}11.5$ months in the study group and $93.0{\pm}30.3$ months in the control group (P=0.049). In the survival analysis, it was investigated that TNM stage and the resection margin involvement of the frozen section diagnosis were the critical variables. Conclusions: When the tumor is located at the middle or the upper third, or the Lauren's indeterminate type, they are highly likely to show the resection margin involvement on the frozen section diagnosis, and it can, therefore, have negative effects on the prognosis. It is considered as good to perform more extensive resection as possible, during the initial resection.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.123-129
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• 2015

$^{64}Cu$-labeled diacetyl-bis($N^4$-methylthiosemicarbazone) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the study, we confirmed hypoxia regions in VX2 tumor implanted rabbits with injection $^{64}Cu$-ATSM and $^{18}F$-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with $^{18}F$-FDG and $^{64}Cu$-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of $^{64}Cu$-ATSM the acquired up to 48 hours. Correlation between intratumoral $O_2$ level and $^{64}Cu$-ATSM PET image was analyzed. $^{64}Cu$-ATSM and $^{18}F$-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, $^{64}Cu$-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for48 h. The uptake pattern of $^{64}Cu$-ATSM in VX2 tumor at 24 and 48 h did not match to the $^{18}F$-FDG. Through ROI analysis, in the early phase (dynamic scan), $^{18}F$-FDG has positive correlation with $^{64}Cu$-ATSM but late phase (24 and 48 h) of the $^{64}Cu$-ATSM showed negative correlation with $^{18}F$-FDG. High uptake of $^{64}Cu$-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by $^{64}Cu$-ATSM PET imaging and autoradiographic analysis. In conclusion, $^{64}Cu$-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue.

• BMB Reports
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• v.55 no.4
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• pp.198-203
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• 2022

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

• Molecules and Cells
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• v.45 no.12
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• pp.886-895
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• 2022

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

• Journal of the Korean Orthopaedic Association
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• v.54 no.6
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• pp.509-518
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• 2019

Purpose: Lymph node metastasis is a very important prognostic factor for all skin cancers and some sarcomas. A sentinel lymph node (SLN) biopsy is the most useful technique for identifying SLNs. Recently, a new generation of diagnostic tools, such as single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/CT (PET/CT) enabled the detection of SLNs. This study compared the efficacy of PET/CT for detecting lymph node metastases with a SLN biopsy in a single medical center. Materials and Methods: From 2008 to 2018, 72 skin cancers of sarcoma patients diagnosed with some lymph node involvement in a whole body PET/CT reading were assessed. Patients suspected of lymph node metastasis were sent to biopsy and those suspected to be reactive lesions were observed. The analysis was performed retrospectively using the medical records, clinical information, PET/CT readings, and pathology results. Results: The age of patients ranged from 14 to 88 years and the mean follow-up period was 2.4 years. Twenty-two patients were suspected of a lymph node metastasis and confirmed. The sensitivity, specificity, positive predictive value and negative predictive value of PET/CT images in sarcoma and non-sarcoma tumors were increased significantly when the expert's findings were considered together. Conclusion: PET/CT is effective in detecting lymph node metastases.

• Korean Journal of Radiology
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• v.24 no.5
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• pp.384-394
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• 2023

Objective: Mammographic density is an independent risk factor for breast cancer that can change after neoadjuvant chemotherapy (NCT). This study aimed to evaluate percent changes in volumetric breast density (ΔVbd%) before and after NCT measured automatically and determine its value as a predictive marker of pathological response to NCT. Materials and Methods: A total of 357 patients with breast cancer treated between January 2014 and December 2016 were included. An automated volumetric breast density (Vbd) measurement method was used to calculate Vbd on mammography before and after NCT. Patients were divided into three groups according to ΔVbd%, calculated as follows: Vbd (post-NCT - pre-NCT)/pre-NCT Vbd × 100 (%). The stable, decreased, and increased groups were defined as -20% ≤ ΔVbd% ≤ 20%, ΔVbd% < -20%, and ΔVbd% > 20%, respectively. Pathological complete response (pCR) was considered to be achieved after NCT if there was no evidence of invasive carcinoma in the breast or metastatic tumors in the axillary and regional lymph nodes on surgical pathology. The association between ΔVbd% grouping and pCR was analyzed using univariable and multivariable logistic regression analyses. Results: The interval between the pre-NCT and post-NCT mammograms ranged from 79 to 250 days (median, 170 days). In the multivariable analysis, ΔVbd% grouping (odds ratio for pCR of 0.420 [95% confidence interval, 0.195-0.905; P = 0.027] for the decreased group compared with the stable group), N stage at diagnosis, histologic grade, and breast cancer subtype were significantly associated with pCR. This tendency was more evident in the luminal B-like and triple-negative subtypes. Conclusion: ΔVbd% was associated with pCR in breast cancer after NCT, with the decreased group showing a lower rate of pCR than the stable group. Automated measurement of ΔVbd% may help predict the NCT response and prognosis in breast cancer.