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Biomedical subjects

Kyung Hae Jung

Publications and source records attributed to Kyung Hae Jung.

15 recordsLinked to original sources

Quality of life with palbociclib plus tamoxifen in hormone receptor-positive, HER2-negative advanced breast cancer: results from PATHWAY, an Asian international, double-blind, randomized phase 3 trial.

BACKGROUND: In the Asian international PATHWAY trial, palbociclib-tamoxifen demonstrated improved progression-free survival compared with placebo-tamoxifen in patients with HR+/HER2- locally advanced or metastatic breast cancer (ABC). This analysis compared quality of life (QoL) between treatment arms. METHODS: Pre/peri or postmenopausal women with HR+/HER2- ABC were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Patient-reported outcomes were assessed on day 1 of cycles 1 (baseline), 4, and 7, and at the end of treatment (EOT) using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Least-square mean (LSM) changes in scores from baseline were calculated. Kaplan-Meier method was used to calculate time to deterioration (TTD) in the minimally important difference (MID) in the pain subscale. RESULTS: In the comparison between treatment arms, no significant differences were observed in LSM changes in scores from baseline in global QoL (cycle 4: 0.70 [95% confidence interval (CI): -5.00, 6.41]; cycle 7: 2.17 [95% CI: -4.14, 8.48]; EOT: -5.19 [95% CI: -11.64, 1.26]). For both the EORTC QLQ-C30 and QLQ-BR23 functional and symptom subscales, no clinically meaningful differences between treatment arms were found in the LSM changes in scores from baseline. Median TTD in the MID in the pain subscale was 32.5 months (95% CI: 11.7, not estimable) for the palbociclib-tamoxifen arm and 21.2 months (95% CI: 5.5, 43.5) for the placebo-tamoxifen arm (hazard ratio = 0.729 [95% CI: 0.467, 1.138]). CONCLUSIONS: The combination of palbociclib and tamoxifen delayed deterioration in patients' QoL while they experienced reduced risk for disease progression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03423199; study registration date: February 6, 2018.

Humans↗

Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer.

PURPOSE: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. RESULTS: Radiologic examination showed that tumor volume decreased by 68.2% +/- 20.5% in the FL group and 68.3% +/- 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). CONCLUSION: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

Adult↗

Analysis of microsatellite instability in stool DNA of patients with colorectal cancer using denaturing high performance liquid chromatography.

AIM: To evaluate the usefulness of denaturing high performance liquid chromatography (DHPLC) for analyzing microsatellite instability (MSI) status in stool DNA of patients with colorectal cancer. METHODS: A total of 80 cancer tissues from patients with primary sporadic colorectal tumor (proximal cancer: 27, distal cancer: 53) and matched stool (which were employed for comparison with the tissues) were analyzed for MSI status in BAT 26. DNA samples extracted from stool were evaluated by nested polymerase chain reaction (PCR) and DHPLC for MSI analysis. RESULTS: Six cases (7.5%) of MSI were identified in BAT 26 from 80 cancer tissues. All the stool DNA samples from patients whose cancer tissue showed MSI also displayed MSI in BAT 26. CONCLUSION: As MSI is one of the established fecal DNA markers to screen colorectal cancer, we propose to use DHPLC for the MSI analysis in fecal DNA.

Biomarkers, Tumor↗

Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type.

AIMS: To evaluate the histopathological risk factors for lymph node metastasis in cases of pedunculated or semipedunculated submucosal invasive colorectal carcinoma (SICC). METHODS: A total of 48 patients with non-sessile SICC who underwent systematic lymph node dissection were included. Tumour size, histological grade, angiolymphatic invasion, tumour budding, dedifferentiation, objective submucosal invasion depth from the identified muscularis mucosa, relative invasion depth of the submucosal layer, and depth of stalk invasion were investigated histopathologically. RESULTS: Lymph node metastasis was observed in seven cases (14.6%). Univariate analysis showed angiolymphatic invasion and tumour budding to be significantly associated with lymph node metastasis. Multivariate analysis showed that tumour budding was the only independent factor associated with lymph node metastasis in cases of non-sessile SICC. CONCLUSIONS: Results indicate that tumour budding is a useful risk factor for predicting lymph node metastasis in cases of pedunculated or semipedunculated SICC.

Adenocarcinoma↗

Is T classification still correlated with lymph node status after preoperative chemoradiotherapy for rectal cancer?

BACKGROUND: It is well known that the risk of lymph node involvement increases according to pathologic T classification in rectal cancers, but to the authors' knowledge, the correlation between risk of lymph node involvement and ypT classification in rectal cancers treated with preoperative chemoradiotherapy (CRT) remains unclear. The current study investigated the correlation between tumor involvement in regional lymph nodes and rectal mural tumor status in patients who underwent preoperative CRT for rectal cancer. METHODS: Between October 2001 and February 2005, 282 patients underwent preoperative CRT followed by proctectomy for locally advanced rectal adenocarcinoma. Correlations between lymph node status and ypT classification, Dworak regression grade, and magnetic resonance (MR) volumetry findings were explored. RESULTS: Lymph nodes harboring tumors were found in 87 of 282 (30.9%) patients. The rate of lymph node involvement was found to be correlated with ypT-classification (P < .001); positive lymph nodes were detected in 1 of 45 (2.2%) ypT0 patients, 1 of 13 (7.7%) ypT1 patients, 13 of 77 (16.9%) ypT2 patients, 69 of 140 (49.3%) ypT3 patients, and 3 of 7 (42.9%) ypT4 patients. The rate of lymph node involvement decreased as Dworak regression grade increased (P < .001); tumor-harboring lymph nodes were found in 62.3% of Grade 1 patients, 31.4% of Grade 2 patients, 16.1% of Grade 3 patients, and 2.2% of Grade 4 patients. There were no differences noted with regard to MR volumetry findings, including mean volume of pre- or post-CRT tumor and the tumor volume reduction rate between lymph node-negative and lymph node-positive patients. CONCLUSIONS: Pathologic T classification is still the most reliable predictor of lymph node metastasis in rectal cancer patients who have undergone preoperative CRT. The risk of lymph node metastasis was found to be 3.4% in rectal cancer that had regressed to ypT0 or ypT1.

Adenocarcinoma↗

Randomized phase II study of gemcitabine plus cisplatin versus etoposide plus cisplatin for the treatment of locally advanced or metastatic non-small cell lung cancer: Korean Cancer Study Group experience.

BACKGROUND: Several randomized trials have demonstrated superior response rates and survivals for new agent platinum doublets than for older platinum doublets in advanced non-small cell lung cancer (NSCLC), however, few trials have been performed in Asian populations. Thus, we conducted a randomized study to compare gemcitabine-cisplatin (GP) with etoposide-cisplatin (EP) in Korean patients with advanced NSCLC. METHODS: Patients with histologically confirmed, locally advanced or metastatic NSCLC were randomized to receive either gemcitabine 1250 mg/m2 on days 1 and 8 plus cisplatin 75 mg/m2 on day 1, or etoposide 100 mg/m2 on days 1-3 plus cisplatin 75 mg/m2 on day 1. Treatment was repeated every 21 days in both groups. The primary endpoint was response rate. RESULTS: Between May 2000 and December 2001, 83 patients at 9 Korean centers were enrolled in this study. The GP arm showed a significantly higher response rate (52.6% versus 19.4%; P = 0.002), a longer time to progression (4.3 months in both arms; P = 0.018) and a marginally significant prolongation of overall survival (18.3 months versus 10.9 months; P = 0.059) than the EP arm. Grades 3 and 4 thrombocytopenia (18% versus 0%) was more common in the GP arm whereas grades 3 and 4 neutropenia was more common in EP arm (48.7% versus 71.8%). Other toxicities were comparable in both arms. CONCLUSION: GP provided a significantly higher response rate and a longer time to progression than EP and should be considered a standard treatment in advanced NSCLC in Korean population.

Adenocarcinoma↗

Preoperative chemoradiotherapy with concomitant small field boost irradiation for locally advanced rectal cancer: a multi-institutional phase II study (KROG 04-01).

PURPOSE: This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer. METHODS: The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and post-chemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate. RESULTS: Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced > or = Grade 3 acute toxicity. CONCLUSIONS: Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation.

Adult↗

[Radiation therapy for rectal cancer].

The current conventional treatment for locally advanced rectal cancer with stage II or III is surgery following or followed by chemoradiotherapy (CRT), which improved local control and overall survival when compared with surgery alone. Recently, a prospective randomized study with a large sample size and long-term follow-up reported that preoperative CRT resulted in improved local control and sphincter preservation, reduced toxicities, and comparative overall survival when compared with postoperative CRT. However, diagnostic imaging for accurate stage should be applied. In addition, chemotherapeutic regimen, schedule for radiation therapy, and timing of surgery should be also optimized in order to maximize the effect of preoperative CRT.

Combined Modality Therapy↗

Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer.

PURPOSE: We performed magnetic resonance (MR) volumetry before and after neoadjuvant chemoradiation for evaluating response to therapy in T3 and T4 rectal cancer. To investigate the utility of MR volumetry for predicting the response to neoadjuvant chemoradiation, we compared results from MR volumetry before chemoradiation with those after chemoradiation. METHODS AND MATERIALS: A total 112 patients with T3 or T4 rectal cancer who successfully underwent MR volumetry and completed neoadjuvant chemoradiation followed by radical resection for cure were identified. MR volumetries were performed before and after chemoradiation. We compared pre- and postchemoradiation tumor volume and % volume reduction rates of patients whose tumors were down-staged with those of patients that were not down-staged. The same analyses were also performed between those patients having a complete histologic regression and those with residual disease in the operative specimen. We assessed the difference of % volume reduction rate according to Dworak's rectal cancer regression grades. RESULTS: Fifty-seven patients (50.9%) demonstrated a tumor down-staging after chemoradiation therapy. Both pre- and posttreatment MR tumor volumes were significantly less in patients whose tumors were down-staged than in patients that were not down-staged (p = 0.04, 0.031), and % volume reduction rates were significantly higher in patients whose tumors were down-staged (p = 0.024). Sixteen patients (14.3%) showed pathologically complete tumor regression. The differences of MR tumor volumes before and after chemoradiation and % volume reduction rates were not significantly different between patients having a complete histologic regression and those with residual disease (p = 0.688, 0.451, and 0.480). The differences of % volume reduction rates according to Dworak's grades were statistically significant (p = 0.03). CONCLUSION: The MR volumetric examinations before and after chemoradiation demonstrated the significant difference of tumor volume and % volume reduction rate between patients whose tumors were down-staged and those that were not down-staged. The volume reduction rates were significantly different among groups according to Dworak's grades. However, the MR volumetric evaluation could not identify any differences between those patients having a complete histologic regression and those with residual disease.

Adult↗

Comparison of the belly board device method and the distended bladder method for reducing irradiated small bowel volumes in preoperative radiotherapy of rectal cancer patients.

PURPOSE: To determine the most effective method to reduce the irradiated small bowel volume when using a belly board device (BBD), a distended bladder (DB), or both in patients with rectal cancer undergoing preoperative pelvic radiotherapy (RT). METHODS AND MATERIALS: The study involved 20 patients with rectal cancer who were scheduled to receive preoperative pelvic RT. Patients were asked to empty their bladders and then drink 300 mL of water 2 h before the treatment planning computed tomographic (CT) scan. To identify the small bowel, an oral contrast solution (450 mL) was given 1 h before the CT scan. Two sets of transverse images were taken at 1-cm-thickness intervals with patients in the prone position with or without the BBD. After voiding, two additional sets of CT scans were obtained in prone positions with or without BBD. The conventional three-field treatment plan, composed of a 6-MV photon posterior-anterior field and 15-MV photon opposed lateral fields with wedges of 45 degrees, was made using a three-dimensional treatment planning system. The beam weights of the three-field plan were equal. The volume of irradiated small bowel was calculated for doses between 10% and 100% of the prescribed dose at 10% intervals. For each 10% dose increment, the effect of the BBD and the DB on the irradiated volume was analyzed using Kruskal-Wallis, Wilcoxon signed rank, and Wilcoxon rank-sum tests. RESULTS: All patients underwent four sets of CT scan under the conditions of four different methods as follows: Group I = empty bladder without the use of belly board; Group II = empty bladder with the use of belly board; Group III = distended bladder without the use of belly board; Group IV = distended bladder with the use of belly board. We found that the volume of irradiated small bowel decreased in the order of Group I, Group II, Group III, and Group IV at all dose levels (p < 0.05). Compared with Group I, the mean volume reduction rate (reduced volume) of irradiated small bowel in Group II varied between 14.5% and 65.4% (15.5-80.4 cm(3)), in Group III it varied between 48.1% and 82.0% (21.6-163.1 cm(3)), and in Group IV between 51.4% and 96.4% (28.6-167.1 cm(3)). CONCLUSIONS: The DB was more effective than the BBD for reducing the volume of irradiated small bowel in rectal cancer patients receiving pelvic RT. The combination of the BBD and DB showed an additive effect and was the most effective method for reducing the irradiated small bowel volume.

Adult↗

Comparative analysis of the effects of belly board and bladder distension in postoperative radiotherapy of rectal cancer patients.

PURPOSE: To compare the effect of reducing the irradiated small-bowel volume with the use of belly board, bladder distension or both methods combined, in patients with rectal cancer undergoing postoperative pelvic radiotherapy. PATIENTS AND METHODS: This study enrolled 20 consecutive patients with rectal cancer who were scheduled to receive postoperative pelvic radiotherapy. All patients underwent four sets of CT scans under four different methods as follows: group I: empty bladder without the use of a belly board; group II: empty bladder with the use of a belly board; group III: bladder distension without the use of a belly board; group IV: bladder distension with the use of a belly board. The conventional three-field treatment plan was made using a three-dimensional treatment planning system. The irradiated small-bowel volume was calculated at 10% intervals from 10% to 100% of the prescribed dose. RESULTS: The volume of the irradiated small bowel decreased in the order of group I, group II, group III, and group IV at all dose levels (p < 0.001). In comparison to group I, the mean absolute volume reductions (relative volume reduction) of the irradiated small bowel were 41.5 +/- 20.1 cm(3) (33.9 +/- 12.9%) in group II, 76.6 +/- 30.5 cm(3) (55.1 +/- 17.8%) in group III, and 98.5 +/- 36.7 cm(3) (70.7 +/- 14.5%) in group IV. CONCLUSION: Bladder distension was a more effective method than the belly board for reducing the irradiated small-bowel volume in postoperative pelvic radiotherapy of rectal cancer patients. The combination of the belly board and bladder distension showed an additive effect and was the most effective method for reducing the irradiated small-bowel volume.

Adenocarcinoma↗

Bax, a predictive marker for therapeutic response to preoperative chemoradiotherapy in patients with rectal carcinoma.

In an attempt to improve local control and survival in patients with advanced rectal carcinoma, neoadjuvant chemoradiation therapy (CRT) has been increasingly used in patient management. However, a significant proportion of patients shows poor response to adjuvant CRT. Thus, the ability to predict CRT responsiveness in patients with rectal cancer would benefit effective management. Several molecular markers related to regulation of cell cycle, apoptosis, or DNA repair have been proposed as candidate predictors of therapeutic response to CRT, but, to date, none has been definitively proven to be predictive of CRT response. To evaluate the use of various molecular markers as predictors of the response to CRT in rectal carcinoma, we investigated immunohistochemical expressions of p53, p21 WAF1/CIP1 , Bcl-2, Bax, Ki-67, Ku-70, and 2 new candidate markers (histone deacetylase 1 and metabotropic glutamate receptor 4) in pretreatment biopsy samples of 130 rectal carcinomas. We further compared the expressions of these molecular markers with the pathological responses of the tumors after therapy. We found that Bax expression, among the markers studied, was exclusively related to tumor regression. Its expression was significantly higher in the complete response group as compared with the partial response group (54% versus 29%, P = .017). This result confirms that apoptosis plays an important role in tumor response to CRT and provides evidence that Bax may serve as a predictable molecular marker for chemoradiosensitivity in rectal carcinoma.

Adult↗

Cytotoxic effects of pemetrexed in gastric cancer cells.

Pemetrexed is a newly developed multitargeted antifolate with promising clinical activity in many solid tumors including gastric cancer. The aim of the present study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction with cisplatin in gastric cancer cell lines, and to identify genes associated with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed by tetrazolium-based colorimetric assay (MTT assay) and the interaction between pemetrexed and cisplatin was evaluated by the isobologram method. Western immunoblotting and real time RT-PCR analysis of thymidylate synthase (TS), folylpoly-gamma-glutamate synthetase (FPGS) and reduced folate carrier (RFC1) were performed in order to determine whether sensitivity to pemetrexed would be predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic than 5-fluorouracil, with IC50 between 17 and 310 nM in most of the gastric cancer cell lines examined and the pemetrexed/cisplatin combination resulted in additive or synergistic interaction. The protein expressions of TS, FPGS, and RFC1 were significantly associated with IC50 for 5-fluorouracil, but no such association was found for pemetrexed chemosensitivity. The mRNA expressions of RFC1, FPGS and other target and resistance related genes revealed no significant association with pemetrexed sensitivity. In conclusion, pemetrexed is active against gastric cancer cell lines and the pemetrexed/cisplatin combination showed a synergistic or additive interaction, supporting its clinical use in gastric cancer. Drug sensitivity toward pemetrexed could not be predicted by the expressions of TS, RFC1, or FPGS and we suggest that it is determined by interactions between multiple genes.

Antimetabolites, Antineoplastic↗

Case of complete recovery of pancytopenia after treatment of hypopituitarism.

We describe a 55-year-old woman who presented with pancytopenia with a normocytic and normochromic anemia which was progressive despite conventional treatments such as folic acid, vitamin B6, and oxymetholone. Her physical findings and history of a previous massive postpartum hemorrhage suggested Sheehan's syndrome, and the pituitary hormonal studies revealed panhypopituitarism. After 4 months of thyroxine and glucocorticoid replacement therapy, her pancytopenia and bone marrow hypoplasia recovered completely. Pancytopenia is a rare manifestation of a hormonal abnormality, but hematologists need to be aware of panhypopituitarism as a differential diagnosis when women showing features of hypopituitarism present with pancytopenia because it can be reversed with adequate hormone replacement.

Anemia↗

Antitumor activity of SK-7041, a novel histone deacetylase inhibitor, in human lung and breast cancer cells.

BACKGROUND: A class of synthetic histone deacetylase (HDAC) inhibitors, which are hybrids of trichostatin A and MS-275 were previously developed. In this study, the antitumor effects of SK-7041, one of those novel HDAC inhibitors, was evaluated on lung and breast cancer cell lines. MATERIALS AND METHODS: Human lung and breast cancer cells, as well as normal human bronchial epithelial (NHBE) cells were treated with SK-7041, and results were compared with those of cells treated with suberoylanilide hydroxamic acid (SAHA). RESULTS: SK-7041 induced time-dependent histone hyperacetylation and showed more potent cytotoxicity than SAHA in cancer cells. These antiproliferative effects of SK-7041 were due to apoptotic cell death caused by G2/M-phase arrest and to a lesser extent to G1 arrest. Moreover, SK-7041 inhibited cancer cell proliferation more selectively than NHBE cell proliferation. CONCLUSIONS: These results suggest that SK-7041 may have potential anticancer activity.

Acetylation↗