• Journal of Veterinary Science
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• v.22 no.5
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• pp.62.1-62.13
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• 2021

Background: Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies. Objectives: We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs. Methods: Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis. Results: The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant. Conclusions: Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1, can be used as reliable metastasis factors for canine MGT and therapeutic strategy.

• Journal of Korean Neurosurgical Society
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• v.51 no.3
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• pp.127-134
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• 2012

Objective: To analyze the prognostic factors thought to be related with survival time after a spinal metastasis operation. Methods: We retrospectively analyzed 217 patients who underwent spinal metastasis operations in our hospital from 2001 to 2009. Hematological malignancies, such as multiple myeloma and lymphoma, were excluded. The factors thought to be related with postoperative survival time were gender, age (below 55, above 56), primary tumor growth rate (slow, moderate, rapid group), spinal location (cervical, thoracic, and lumbo-sacral spine), the timing of radiation therapy (preoperative, postoperative, no radiation), operation type (decompressive laminectomy with or without posterior fixation, corpectomy with anterior fusion, corpectomy with posterior fixation), preoperative systemic condition (below 5 points, above 6 points classified by Tomita scoring), pre- and postoperative ambulatory function (ambulatory, non-ambulatory), number of spinal metastases (single, multiple), time to spinal metastasis from the primary cancer diagnosis (below 21 months, above 22 months), and postoperative complication. Results: The study cohort mean age at the time of surgery was 55.5 years. The median survival time after spinal operation and spinal metastasis diagnosis were 6.0 and 9.0 months. In univariate analysis, factors such as gender, primary tumor growth rate, preoperative systemic condition, and preoperative and postoperative ambulatory status were shown to be related to postoperative survival. In multivariate analysis, statistically significant factors were preoperative systemic condition (p=0.048) and postoperative ambulatory status (p<0.001). The other factors had no statistical significance. Conclusion: The factors predictive for postoperative survival time should be considered in the surgery of spinal metastasis patients.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.415-423
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• 2018

Objective : To identify the perioperative factors associated with instrument failure in patients undergoing a partial corpectomy with instrumentation (PCI) for spinal metastasis. Methods : We assessed the one hundred twenty-four patients with who underwent PCI for a metastatic spine from 1987 to 2011. Outcome measure was the risk factor related to implantation failure. The preoperative factors analyzed were age, sex, ambulation, American Spinal Injury Association grade, bone mineral density, use of steroid, primary tumor site, number of vertebrae with metastasis, extra-bone metastasis, preoperative adjuvant chemotherapy, and preoperative spinal radiotherapy. The intraoperative factors were the number of fixed vertebrae, fixation in osteolytic vertebrae, bone grafting, and type of surgical approach. The postoperative factors included postoperative adjuvant chemotherapy and spinal radiotherapy. This study was supported by the National Research Foundation grant funded by government. There were no study-specific biases related to conflicts of interest. Results : There were 15 instrumentation failures (15/124, 12.1%). Preoperative ambulatory status and primary tumor site were not significantly related to the development of implant failure. There were no significant associations between insertion of a bone graft into the partial corpectomy site and instrumentation failure. The preoperative and operative factors analyzed were not significantly related to instrumentation failure. In univariable and multivariable analyses, postoperative spinal radiotherapy was the only significant variable related to instrumentation failure (p=0.049 and 0.050, respectively). Conclusion : When performing PCI in patients with spinal metastasis followed by postoperative spinal radiotherapy, the surgeon may consider the possibility of instrumentation failure and find other strategies for augmentation than the use of a bone graft for fusion.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.6
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• pp.282-288
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• 2018

Objectives: The purpose of this study was to evaluate the neck node metastasis pattern and related clinical factors in oral cavity cancer patients. Materials and Methods: In total, 76 patients (47 males, 29 females) with oral squamous cell carcinoma (OSCC) who had no previous malignancies and were not undergoing neoadjuvant concomitant chemoradiotherapy or radiotherapy were selected for analysis. Results: Occult metastases were found in 8 of 52 patients with clinically negative nodes (cN0, 15.4%). Neck node metastases were found in 17 patients (22.4%). There was a statistically significant relationship between neck node metastasis and T stage (P=0.014) and between neck node metastasis and distant metastasis (Fisher's exact test, P=0.019). Conclusion: Neck node metastasis was significantly related to tumor size and distant metastasis during follow-up.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.6
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• pp.499-508
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• 2007

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9673-9678
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• 2014

Background: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Materials and Methods: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. Results: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Conclusions: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

• Korean Journal of Head & Neck Oncology
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• v.23 no.2
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• pp.138-141
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• 2007

Objectives : Well differentiated thyroid carcinoma(WDTC) has relatively good prognosis. But recurrence is associated with increased morbidity and mortality, and always results in reoperation. So it is important to evaluate the risk factors relative to the recurrence. The aim of this study is to evaluate the risk factors of recurrence. Materials and Method : Two hundred seventeen patients who had undergone thyroidectomy and proved as WDTC from January 1999 to December 2004 was included in the study. We reviewed patient-related and tumorrelated factors respectively and analyzed the correlation with tumor recurrence. Results : Fourteen patients from two hundreds seventeen had recurred. Recurrence rate was 6.5%, and average interval of recurrence was 28 month. Male, age over 45, multiple mass, and advanced TMN stage patient group show higher recurrence rate, but no statistical significance. However, the recurrence rate of lymph node metastasis, tumor size>1.5cm, and extracapsular invasion group were statistically high. Conclusion : Lymph node metastasis, tumor size and extracapsular invasion are significant risk factors related to the recurrence of WDTC.

• Journal of Chest Surgery
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• v.32 no.10
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• pp.916-923
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• 1999

Background: Many institutes are interested in lung metastatectomy than before because of the improved long term survival, low mortality, and low morbidity after lung metastatectomy. However, prognostic factors affecting long term survival are controversial. We attempt to analyze the prognostic factors affecting retrospectively by comparing the results of lung metastasectomy. Material and Method: Between Jan. 1990 and Dec. 1997, 74 operations were taken in 63 patients with pulmonary metastases in various primary sites. We analyzed the postoperative long term survival according to sex, cell type, laterality, disease free interval(DFI), operation, the number of metastases, and the size of the largest metastasis. Result: There were 27 male and 36 female patients. Sex did not appeared to affect survival time(p=0.849). The primary tumor was carcinoma in 32, sarcoma in 28, and others in 3. Cell type, considering carcinoma and sarcoma, did not relate to survival time(p=0.071). DFI had no influence on the outcome(p=0.902). The type of operative procedure had no influence on the outcome(p=0.556). The laterality of metastases, 47 unilateral(74.6%) and 16 bilateral(25.4%), had no influence on the outcome(p=0.843). The number of metastases excised(one, two or three, four or more) did not appear to affect survival(p=0.263). The size of largest metastasis(<=10mm, 11mm-30mm, and >30mm) did not appear to affect survival(p=0.751). Previous factors were evaluated in both the carcinoma and sarcoma patients respectively. DFI was the only significant prognostic factor in metastatic lung sarcoma(p=0.0026). Conclusion: Survival was not related to sex, cell type, laterality, DFI, operative procedure, number of metastases, nor the size of the largest metastasis. DFI was related to the survival time in sarcoma group but further study is needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2953-2957
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• 2016

Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked ${\beta}2-adrenergic$ receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. Materials and Methods: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel-Haenszel, Student t, and ANOVA tests were performed for data analysis. Results: On average, patients were $54.8{\pm}11.8$ years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for ${\beta}1$ - and ${\beta}2$ -adrenergic-receptors did not present metastasis globally, but patients treated with ${\beta}1$ BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. Conclusions: In Mexican patients with BCa and SAH treated with non-selective (${\beta}1$- and ${\beta}2-adrenergic$ receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.