• Journal of Chest Surgery
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• v.52 no.4
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• pp.221-226
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• 2019

Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.

• Advances in nano research
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• v.12 no.6
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.28-34
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• 2022

Glioblastoma is the most common primary malignant brain tumor and has an extremely poor prognosis. Glioblastoma stem cells (GSCs) contribute to tumor initiation, recurrence, and resistance to therapy, and are thus a key therapeutic target. The peel of Citrus unshiu Markovich has been used in traditional medicine in East Asia to treat various diseases. In this study, we investigated the anticancer activity and molecular mechanism of the chloroform extract of this natural product (CECU) in U87MG GSCs. The results show that CECU inhibited the proliferation, tumorsphere formation, and migration of U87MG GSCs by causing cell cycle arrest at the G0/G1 phase and apoptosis. In addition, CECU downregulated key cancer stemness regulators, including CD133, Oct4, Nanog, integrin α6, ALDH1A1, and STAT3 signaling in U87MG GSCs. Furthermore, CECU significantly suppressed in vivo tumor growth of U87MG GSCs in a chorioallantoic membrane model. Therefore, CECU can be utilized as a natural medicine for the prevention and treatment of glioblastoma.

• Journal of Cardiovascular Imaging
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• v.30 no.3
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• pp.185-196
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• 2022

BACKGROUND: Two-dimensional (2D) strain provides more predictive power than ejection fraction (EF) in patients with ST-elevation myocardial infarction (STEMI). 3D strain and EF are also expected to have better clinical usefulness and overcome several inherent limitations of 2D strain. We aimed to clarify the prognostic significance of 3D strain analysis in patients with STEMI. METHODS: Patients who underwent successful revascularization for STEMI were retrospectively recruited. In addition to conventional parameters, 3D EF, global longitudinal strain (GLS), global area strain (GAS), as well as 2D GLS were obtained. We constructed a composite outcome consisting of all-cause death or re-hospitalization for acute heart failure or ventricular arrhythmia. RESULTS: Of 632 STEMI patients, 545 patients (86.2%) had a reliable 3D strain analysis. During median follow-up of 49.5 months, 55 (10.1%) patients experienced the adverse outcome. Left ventricle EF, 2D GLS, 3D EF, 3D GLS, and 3D GAS were significantly associated with poor outcomes. (all, p < 0.001) The maximum likelihood-ratio test was performed to evaluate the additional prognostic value of 2D GLS or 3D GLS over the prognostic model consisting of clinical characteristics and EF, and the likelihood ratio was 15.9 for 2D GLS (p < 0.001) and 1.49 for 3D GLS (p = 0.22). CONCLUSIONS: The predictive power of 3D strain was slightly lower than the 2D strain. Although we can obtain 3D strains, volume, and EF simultaneously in same cycle, the clinical implications of 3D strains in STEMI need to be investigated further.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.301-317
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• 2005

The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.

• The Journal of Korean Academy of Prosthodontics
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• v.52 no.4
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• pp.305-311
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• 2014

Purpose: When the full veneer crown was treated in the tooth with abfraction lesion due to various causes, the prognosis of it may be compromised according to the location of the finish line, but there is few study about the location of its buccal finish line. The purpose of this study was to investigate the effect of location of the finish line of the full veneer crown on stress distribution of the tooth with abfraction lesion. Materials and methods: The two dimensional finite element model was developed to express tooth, surrounding tissue and full veneer crown. The stress distribution under eccentric 144 N occlusal load was analyzed using finite element analysis. The location of finish line was set just at the lower border of the lesion (Group 0), 1 mm (Group 1) and 2 mm (Group 2) below the lower border of the lesion. Results: In the Group 0, von Mises stress was concentrated at the finish line and the apex of the lesion. Also, the stress at the bucal finish line propagated to the lingual side. In the Group 1 and Group 2, stress distribution was similar each other. Stress was concentrated at the apex of lesion, but the stress at the buccal finish line did not propagate to the lingual side. That implied decrease of the possibility of horizontal crown fracture. Conclusion: Full veneer crown alleviated the stress concentrated at the apex of the abfraction lesion, when the finish line of full veneer crown was set below the lower border of abfraction lesion.

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.62-73
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• 2000

Purpose: Esophageal cancer patients have a difficulty in the intake of meals through the blocked esophageal lumen, which is caused by an ingrowth of cancer cells and largely influences on the prognosis. It is reported that esophageal cancer has a very low survival rate due to the lack of nourishment and immunity as the result of this. In this study a new radioactive stent, which prevents tumor ingrowth and restenosis by additional radiation treatment, has been developed. Materials and Methods: Using ${\ulcorner}HANARO{\lrcorner}$ research reactor, the radioactive stent assembly ($^{166}Ho$-SA) was prepared by covering the metallic stent with a radioactive sleeve by means of a post-irradiation and pre-irradiation methods. Results: Scanning electron microscopy and autoradiography exhibited that the distribution of $^{165/166}Ho\;(NO_3)$ compounds in polyurethane matrix was homogeneous. A geometrical model of the esophagus considering its structural properties, was developed for the computer simulation of energy deposition to the esophageal wall. The dose distributions of $^{166}Ho$-stent were calculated by means of the EGS4 code system. The sources are considered to be distributed uniformly on the surface in the form of a cylinder with a diameter of 20 mm and length of 40 mm. As an animal experiment, when radioactive stent developed in this study was inserted into the esophagus of a Mongrel dog, tissue destruction and widening of the esophageal lumen were observed. Conclusion: We have developed a new radioactive stent comprising of a radioactive tubular sleeve covering the metallic stent, which emits homogeneous radiation. If it is inserted into the blocked or narrowed lumen, it can lead to local destruction of the tumor due to irradiation effect with dilatation resulting from self-expansion of the metallic property. Accordingly, it is expected that restenosis esophageal lumen by the continuous ingrowth and infiltration of cancer after insertion of our radioactive stent will be decreased remarkably.

• Journal of Trauma and Injury
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• v.25 no.2
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• pp.49-56
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• 2012

Purpose: For determining the prognosis of critically injured patients, transporting patients to medical facilities capable of providing proper assessment and management, running rapid assessment and making rapid decisions, and providing aggressive resuscitation is vital. Considering the high mortality and morbidity rates in critically injured patients, various studies have been conducted in efforts to reduce those rates. However, studies related to diagnostic factors for predicting severity in critically injured patients are still lacking. Furthermore, patients showing stable vital signs and alert mental status, who are injured via a severe trauma mechanism, may be at a risk of not receiving rapid assessment and management. Thus, this study investigates diagnostic factors, including physical examination and laboratory results, that may help predict severity in trauma patients injured via a severe trauma mechanism, but showing stable vital signs. Methods: From March 2010 to December 2011, all trauma patients who fit into a diagnostic category that activated a major trauma team in CHA Bundang Medical Center were analyzed retrospectively. The retrospective analysis was based on prospective medical records completed at the time of arrival in the emergency department and on sequential laboratory test results. PASW statistics 18(SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Patients with relatively stable vital signs and alert mental status were selected based on a revised trauma score of more than 7 points. The final diagnosis of major trauma was made based on an injury severity score of greater than 16 points. Diagnostic variables include systolic blood pressure and respiratory rate, glasgow coma scale, initial result from focused abdominal sonography for trauma, and laboratory results from blood tests and urine analyses. To confirm the true significance of the measured values, we applied the Kolmogorov-Smirnov one sample test and the Shapiro-Wilk test. When significance was confirmed, the Student's t-test was used for comparison; when significance was not confirmed, the Mann-Whitney u-test was used. The results of focused abdominal sonography for trauma (FAST) and factors of urine analysis were analyzed using the Chi-square test or Fisher's exact test. Variables with statistical significance were selected as prognostics factors, and they were analyzed using a multivariate logistics regression model. Results: A total of 269 patients activated the major trauma team. Excluding 91 patients who scored a revised trauma score of less than 7 points, 178 patients were subdivided by injury severity score to determine the final major trauma patients. Twenty-one(21) patients from 106 major trauma patients and 9 patients from 72 minor trauma patients were also excluded due to missing medical records or untested blood and urine analysis. The investigated variables with p-values less than 0.05 include the glasgow coma scale, respiratory rate, white blood cell count (WBC), serum AST and ALT, serum creatinine, blood in spot urine, and protein in spot urine. These variables could, thus, be prognostic factors in major trauma patients. A multivariate logistics regression analysis on those 8 variables showed the respiratory rate (p=0.034), WBC (p=0.005) and blood in spot urine (p=0.041) to be independent prognostic factors for predicting the clinical course of major trauma patients. Conclusion: In trauma patients injured via a severe trauma mechanism, but showing stable vital signs and alert mental status, the respiratory rate, WBC count and blood in the urine can be used as predictable factors for severity. Using those laboratory results, rapid assessment of major trauma patients may shorten the time to diagnosis and the time for management.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.766-771
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• 2009

Purpose : The objective of this study was to compare the levels of adipocytokines in obesity group with those in control group and examine their correlation with insulin resistance. Methods : We enrolled 36 obese children (male:female [M:F]=17:19; age, $9.3{\pm}1.9yrs$) with ${\geq}95^{th}$ percentile body mass indexes (BMIs) (obesity group) and 35 healthy children (M:F=16:19; age, $9.1{\pm}2.1yrs$) with $25^{th}-75^{th}$ percentile BMIs (control group). We measured the serum leptin, adiponectin, and resistin levels and insulin resistance in both the groups. Results : The weights, heights, BMIs, fasting sugar levels, insulin levels, and homeostasis model assessment for insulin resistance (HOMA-IR) values were higher in the obesity group than in the control group. As compared to the control group, the obesity group showed significantly higher leptin levels and lower adiponectin levels; no significant difference was observed in the resistin levels. The leptin/adiponectin (L/A) ratio was higher in the obesity group than in the control group. In the obesity group, HOMA-IR showed significant positive correlations with weight, height, BMI, and leptin level. However, it was not correlated with age and adiponectin and resistin levels. In the obesity group, leptin level showed significant positive correlations with age, weight, height, and BMI, while adiponectin and resistin levels showed no such correlations with the other variables. Conclusion : We suggest that adiponectin plays an important protective role against weight gain in obese children. Further, L/A ratio can be used as a parameter for predicting the prognosis of obese children.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1811-1815
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• 2014

Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.