• Korean Journal of Radiology
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• 제22권3호
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• pp.425-434
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• 2021

Objective: To investigate the potential value of ¹⁸F-fluorodeoxyglucose (FDG) PET/CT in predicting the survival of patients with primary tracheal malignant tumors. Materials and Methods: An analysis of FDG PET/CT findings in 37 primary tracheal malignant tumor patients with a median follow-up period of 43.2 months (range, 10.8-143.2 months) was performed. Cox proportional hazards regression analyses were used to assess the associations between quantitative ¹⁸F-FDG PET/CT parameters, other clinic-pathological factors, and overall survival (OS). A risk prognosis model was established according to the independent prognostic factors identified on multivariate analysis. A survival curve determined by the Kaplan-Meier method was used to assess whether the prognosis prediction model could effectively stratify patients with different risks factors. Results: The median survival time of the 37 patients with tracheal tumors was 38.0 months, with a 95% confidence interval of 10.8 to 65.2 months. The 3-year, 5-year and 10-year survival rate were 54.1%, 43.2%, and 16.2%, respectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value, age, pathological type, extension categories, and lymph node stage were included in multivariate analyses. Multivariate analysis showed MTV (p = 0.011), TLG (p = 0.020), pathological type (p = 0.037), and extension categories (p = 0.038) were independent prognostic factors for OS. Additionally, assessment of the survival curve using the Kaplan-Meier method showed that our prognosis prediction model can effectively stratify patients with different risks factors (p < 0.001). Conclusion: This study shows that ¹⁸F-FDG PET/CT can predict the survival of patients with primary tracheal malignant tumors. Patients with an MTV > 5.19, a TLG > 16.94 on PET/CT scans, squamous cell carcinoma, and non-E1 were more likely to have a reduced OS.

• Genomics & Informatics
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• 제19권1호
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• pp.5.1-5.11
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• 2021

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1563-1566
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• 2014

Background: Esophageal squamous cell carcinoma (ESCC) accounts for most esophageal cancer in Asia, and is the sixth common cause of cancer-related deaths worldwide. Previous studies indicated HOXB7 is overexpressed in ESCC tissues, but data on prognostic value are limited. Methods: A total of 76 advanced ESCC cases were investigated. Immunohistochemistry (IHC) was used to detect the expression levels of HOXB7 and Kaplan-Meier curves and Cox regression models to determine prognostic significance. Stratified analysis was also performed according to lymph node (LN) status. Results: Kaplan-Meier curve analysis indicated that HOXB7 positive patients had significantly shorter overall survival (OS) than HOXB7 negative patients. Multivariate analysis using the Cox proportional hazards model indicated only TNM stage and HOXB7 expression to be independent predictors of overall survival of advanced ESCC patients. HOXB7 indicated poor OS in both lymph node negative (LN-) and lymph node positive (LN+) patients. Conclusion: HOXB7 predicts poor prognosis of advanced ESCC patients and can be applied as an independent prognostic predictor.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.199-203
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• 2012

Purpose: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). Methods: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. Results: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). Conclusions: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

• 한국통계학회:학술대회논문집
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• 한국통계학회 2005년도 춘계 학술발표회 논문집
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• pp.17-23
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• 2005

In this paper we consider the well-known semiparametric proportional hazards models for survival analysis. These models are usually used with few covariates and many observations (subjects). But, for a typical setting of gene expression data from DNA microarray, we need to consider the case where the number of covariates p exceeds the number of samples n. For a given vector of response values which are times to event (death or censored times) and p gene expressions(covariates), we address the issue of how to reduce the dimension by selecting the significant genes. This approach enables us to estimate the survival curve when n ${\ll}$p. In our approach, rather than fixing the number of selected genes, we will assign a prior distribution to this number. The approach creates additional flexibility by allowing the imposition of constraints, such as bounding the dimension via a prior, which in effect works as a penalty To implement our methodology, we use a Markov Chain Monte Carlo (MCMC) method. We demonstrate the use of the methodology to diffuse large B-cell lymphoma (DLBCL) complementary DNA (cDNA) data and Breast Carcinomas data.

• Radiation Oncology Journal
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• 제4권2호
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• pp.89-97
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• 1986

Co-60 치료기로 마우스 전신에 다분할조사(단일 2, 3, 4, 5, 8, 10, 12, 16회 분할 조사)후 공장소 낭선세포측정법으로 소낭선세포의 재생능력에 대한 선량반응 곡선을 작성하고, 단일선량생존곡선을 분석하여 다음과 같은 결론을 얻었다. 1) 분할조사회수가 증가함에 따라 생존곡선은 고선량으로 이동하고 경사도는 점차 낮아졌다. 2) 단일선량생존곡선에서 Dq=460 cGy로 비교적 broad shoulder를 가지며 initial slope$(^1Do)$는 475 cGy이 었다. 3) $180\~450cGy$까지 분할 조사한 경우 분할조사간격당 평균회복선량은 분할조사선량의 약 $50\%$이었다. 4) 등가효과를 나타내는 분할조사선량과 이에 해당하는 총선량의 역수를 산출하여 선형회귀분석한 $\alpha/\beta$ 값은 8.3Gy로 조기반응조직의 범위(6-l4Gy)에 속하였다. 5) LQ model은 방사선치료에 사용되고 있는 모든 선량에 적용이 가능하고, $\alpha,\;\beta$ 두 요소만 필요하므로, 실질적으로 편리하게 적응할 수 없다. 다분할조사에 대한 stem cell의 반응을 이해함으로써, 실제방사선치료시 위장관에 대한 급성손상을 극소화시키는 변형된 치료방법을 도입하고 다른 조직에도 응용할 수 있는 방사선생물학적 자료가 될 것으로 사료된다.

• Radiation Oncology Journal
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• 제7권2호
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• pp.171-183
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• 1989

Roesch의 생존 방정식속에 세포증식으로 일어나는 생존증가를 가장 일반적 형식으로 포함시킨 식을 유도하고 이 식으로부터 저선량률 방사선에만 적용되는 동결과선량식 (Isoeffect formula)을 유도하였다. 이 저선량률식이 파라메터 하나로 결정해주는 총선량은 Paterson과 Green에 의하여 얻어진 실험 임상결과와 일치한다. 이 파라메터와 선량률 효과 사이의 관계의 의의를 논하였다. 또한 고선량률 분절(fractionation) 치료와 동저선량률 계속치료를 연락하는 동결과 선량식을 유도 사용하여, Ellis가 잰 실험결과와 비교하였다. 그 결과, Ellis와 Paterson이 쓴 'tolerance'의 표준이 $\alpha/\beta$의 비 4Gy에 해당하는 것임이 밝혀졌다. 그러므로 이들의 'tolerance'의 표준은 'early effect'에만 두고 본 것이 아님을 알 수 있다. 개념적인 면에서도, 아래와 같은 새로운 견해가 나올 수 있다. KHT sarcoma의 생존선도 (survival curve)에 선량률 효과가 보이지 않는 이유로 $\alpha/\beta$의 비가 큰 점을 들을 수 있다. 이것은 이 survival curve에 어께 (shoulder)가 보이지 않는 것으로도 증명이 된다. Pierquin이 선량률에 무관하게 head and neck tumor치료에 같은 총선량을 쓴 것을 정당화시킬 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.871-876
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• 2014

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters. Methods: The mRNA expression of DSGs, as well as ${\gamma}$-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens. Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p=0.000). DSG3 mRNA expression highly correlated with histological grade (p=0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p=0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of ${\gamma}$-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules. Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.66-73
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• 2009

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

• Journal of Chest Surgery
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• 제55권3호
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• pp.214-224
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• 2022

Background: Studies of the prognostic role of circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (NSCLC) are still limited. This study investigated the prognostic power of CTCs from the pulmonary vein (PV), peripheral blood (PB), and bone marrow (BM) for postoperative recurrence in patients who underwent curative resection for NSCLC. Methods: Forty patients who underwent curative resection for NSCLC were enrolled. Before resection, 10-mL samples were obtained of PB from the radial artery, blood from the PV of the lobe containing the tumor, and BM aspirates from the rib. A microfabricated filter was used for CTC enrichment, and immunofluorescence staining was used to identify CTCs. Results: The pathologic stage was stage I in 8 patients (20%), II in 15 (38%), III in 14 (35%), and IV in 3 (8%). The median number of PB-, PV-, and BM-CTCs was 4, 4, and 5, respectively. A time-dependent receiver operating characteristic curve analysis showed that PB-CTCs had excellent predictive value for recurrence-free survival (RFS), with the highest area under the curve at each time point (first, second, and third quartiles of RFS). In a multivariate Cox proportional hazard regression model, PB-CTCs were an independent risk factor for recurrence (hazard ratio, 10.580; 95% confidence interval, 1.637-68.388; p<0.013). Conclusion: The presence of ≥4 PB-CTCs was an independent poor prognostic factor for RFS, and PV-CTCs and PB-CTCs had a positive linear correlation in patients with recurrence.