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Clinicopathologic Characteristics in Node-negative Gastric Cancer Patients According to the Presence of Lymphatic Invasion

  • Choi, Ji-Yoon;Ha, Tae-Kyoung;Kwon, Sung-Joon
    • Journal of Gastric Cancer
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    • v.10 no.2
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    • pp.55-62
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    • 2010
  • Purpose: We evaluated the clinicopathological charicterics and prognostic impacts of lymphatic vessel invasion in gastric cancer without lymph node involvement. Materials and Methods: Among 1,795 patients who underwent gastric surgery with gastric cancer at the department of surgery, Hanyang university college of medicine from June 1992 to March 2009, we retrospectively evaluated 890 patients with lymph node negative gastric cancer. Results: The lymphatic vessel invasion correlated significantly with tumor stage, age, tumor size, perineural invasion and operation method. The survival rates were only significantly different between the patients with and without lymphatic vessel invasion in patients with stage Ia (P=0.036). Univariate and multivariate analysis demonstrated that blood vessel invasion and preoperative serum CEA level were significant factor influencing the survival rate in lymph node negative gastric cancer patients with lymphatic invasion. Conclusions: In patients with lymph node negative gastric cancer, the survival rate is significantly lower in those with lymphatic vessel invasion than in those without. Especially, in patients with stage Ia gastric cancer, the survival rates is significantly different between those with and those without lymphatic vessel invasion. Blood vessel invasion and preoperative serum CEA level is an adverse prognostic indicator in patients with stage Ia gastric cancer with lymphatic invasion. Thus we should consider further adjuvant therapies in case of need and need to show more concern to identify gastric cancer patients early at risk for recurrence.

Role of proteases, cytokines, and growth factors in bone invasion by oral squamous cell carcinoma

  • Son, Seung Hwa;Chung, Won-Yoon
    • International Journal of Oral Biology
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    • v.44 no.2
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    • pp.37-42
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    • 2019
  • Oral squamous cell carcinoma (OSCC) is the most common oral malignancy and an increasing global public health problem. OSCC frequently invades the jaw bone. OSCC-induced bone invasion has a significant impact on tumor stage, treatment selection, patient outcome, and quality of life. A number of studies have shown that osteoclast-mediated bone resorption is a major step in the progression of bone invasion by OSCC; however, the molecular mechanisms involved in OSCC bone invasion are not yet clear. In this review, we present the clinical types of OSCC bone invasion and summarize the role of key molecules, including proteases, cytokines, and growth factors, in the sequential process of bone invasion. A better understanding of bone invasion will facilitate the discovery of molecular targets for early detection and treatment of OSCC bone invasion.

Significances of Minimal Extrathyroidal Invasion in Papillary Thyroid Carcinoma (유두상 갑상선암에서 최소 갑상선외 침범의 의의)

  • Lee, Byoung-Kil;Lee, Min-Joo;Youn, Hyun-Jo;Jung, Sung-Hoo
    • Korean Journal of Head & Neck Oncology
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    • v.25 no.1
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    • pp.8-11
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    • 2009
  • Background and Objectives : In the TNM 6th classification system, extrathyroidal invasion of differentiated thyroid carcinoma has been classified into T3(minimal invasion), T4a(extended invasion), and T4b(more extensive unresectable invasion) according to the degree and it has been recognized as an important prognostic factor. In this study, we investigated the prognostic significances of minimal extrathyroidal invasion in papillary thyroid carcinoma(PTC). Material and Methods : We retrospectively studied 221 patients who are underwent thyroidectomy due to PTC from September 2003 to December 2006. Fifty-four(24.4%) patients had a PTC with minimal extrathyroidal invasion(Group A) and 167(75.6%) patients had a PTC without extrathyroidal invasion(Group B). The existence of minimal extrathyroidal invasion was based on operative and pathological findings. Results : Minimal extrathyroidal invasion in PTC was related to tumor size, lymph node metastasis, and operative method(p<0.001). But, there is no significant difference in age, gender, and multifocality between Group A and B. Hashimoto's thyroiditis was observed more frequently in Group B(p=0.019). Conclusion : These findings suggest that minimal extrathyroidal invasion is related to poor prognostic factors in PTC. Therefore, aggressive surgical approach is required when there is evidence of minimal extrathyroidal invasion in preoperative radiologic examination or operative finding.

Transglutaminase-2 Is Involved in All-Trans Retinoic Acid-Induced Invasion and Matrix Metalloproteinases Expression of SH-SY5Y Neuroblastoma Cells via NF-κB Pathway

  • Lee, Hye-Ja;Park, Mi-Kyung;Bae, Hyun-Cheol;Yoon, Hee-Jung;Kim, Soo-Youl;Lee, Chang-Hoon
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.286-292
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    • 2012
  • All-trans retinoic acid (ATRA) is currently used in adjuvant differentiation-based treatment of residual or relapsed neuroblastoma (NB). It has been reported that short-term ATRA treatment induces migration and invasion of SH-SY5Y via transglutaminase-2 (Tgase-2). However, the detailed mechanism of Tgase-2's involvement in NB cell invasion remains unclear. Therefore we investigated the role of Tgase-2 in invasion of NB cells using SH-SY5Y cells. ATRA dose-dependently induced the invasion of SH-SY5Y cells. Cystamine (CTM), a well known tgase inhibitor suppressed the ATRA-induced invasion of SH-SY5Y cells in a dose-dependent manner. Matrix metalloproteinase -9 (MMP-9) and MMP-2, well known genes involved in invasion of cancer cells were induced in the ATRA-induced invasion of the SH-SH5Y cells. Treatment of CTM suppressed the MMP-9 and MMP-2 enzyme activities in the ATRA-induced invasion of the SH-SY5Y cells. To confirm the involvement of Tgase-2, gene silencing of Tgase-2 was performed in the ATRA-induced invasion of the SH-SH5Y cells. The siRNA of Tgase-2 suppressed the MMP-9 and MMP-2 activity of the SH-SY5Y cells. MMP-2 and MMP-9 are well known target genes of NF-${\kappa}B$. Therefore the relationship of Tgase-2 and NF-${\kappa}B$ in the ATRA-induced invasion of the SH-SY5Y cells was examined using siRNA and CTM. ATRA induced the activation of NF-${\kappa}B$ in the SH-SY5Y cells and CTM suppressed the activation of NF-${\kappa}B$. Gene silencing of Tgase-2 suppressed the MMP expression by ATRA. These results suggested that Tgase-2 might be a new target for controlling the ATRA-induced invasion of NBs.

Different invasion efficiencies of Brucella abortus wild-type and mutants in RAW 264.7 and THP-1 phagocytic cells and HeLa non-phagocytic cells

  • Shim, Soojin;Im, Young Bin;Jung, Myunghwan;Park, Woo Bin;Yoo, Han Sang
    • Korean Journal of Veterinary Research
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    • v.58 no.2
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    • pp.95-98
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    • 2018
  • Brucellosis is one of the common zoonoses caused by Brucella abortus (B. abortus). However, little has been reported on factors affecting invasion of B. abortus into host cells. To investigate cell-type dependent invasion of B. abortus, phagocytic RAW 264.7 and THP-1 cells and non-phagocytic HeLa cells were infected with wild-type and mutant B. abortus, and their invasion efficiencies were compared. The invasion efficiencies of the strains were cell-type dependent. Wild-type B. abortus invasion efficiency was greater in phagocytic cells than in epithelial cells. The results also indicated that there are different factors involved in the invasion of B. abortus into phagocytic cells.

Accuracy of Intraoperative Gross Examination of Myometrial Invasion in Stage I-II Endometrial Cancer

  • Sethasathien, Prauk;Charoenkwan, Kittipat;Siriaunkgul, Sumalee
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7061-7064
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    • 2014
  • Background: To assess the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of intraoperative gross examination (IGE) of uterine specimens in determining deep myometrial invasion and cervical invasion compared to final histology. Materials and Methods: The clinical, surgical and histological data of all FIGO stage I-II endometrial cancer (EC) patients who had primary surgery were reviewed. Results of the IGE for myometrial invasion and cervical invasion were compared to the final histology. The sensitivity, specificity, PPV, NPV, and accuracy of the IGE in determining deep myometrial invasion and cervical invasion were calculated. Association between clinico-pathological factors and discrepancy between IGE and final histology in the determination of myometrial invasion was also assessed. A p-value of <0.05 was considered significant. Results: From January 2007 to December 2012, 179 patients diagnosed with clinical stage I-II endometrial cancer underwent surgical staging. The sensitivity and specificity of IGE in detecting deep myometrial invasion were 42.4% and 90.0%, respectively, and the PPV and NPV were 67.6% and 76.1%. The overall accuracy of IGE was 74.3%. The sensitivity and specificity of IGE in identifying cervical invasion were 28.6% and 97.5%, respectively, while the PPV and NPV were 60.0% and 91.1%. The overall accuracy of IGE was 89.4%. Conclusions: The sensitivity of IGE for detecting deep myometrial invasion and cervical invasion in early-stage EC is too low to be used alone. Alternative methods including intraoperative frozen section analysis, preoperative three dimensional ultrasound, and preoperative magnetic resonance imaging should be strongly considered.

Prognostic Significance of Hes-1, a Downstream Target of Notch Signaling in Hepatocellular Carcinoma

  • Zou, Jing-Huai;Xue, Tong-Chun;Sun, Chun;Li, Yan;Liu, Bin-Bin;Sun, Rui-Xia;Chen, Jie;Ren, Zheng-Gang;Ye, Sheng-Long
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3811-3816
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    • 2015
  • Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

Proteases are Modulated by Fascin in Oral Cancer Invasion

  • Lee, Min Kyeong;Park, Ji Hyeon;Gi, Seol Hwa;Hwang, Young Sun
    • Journal of Cancer Prevention
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    • v.23 no.3
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    • pp.141-146
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    • 2018
  • Background: Cancer invasion is a critical factor for survival and prognosis of patients with cancer. Identifying and targeting factors that influence cancer invasion are an important strategy to overcome cancer. In this study, we investigated the role of fascin known to be associated with cancer invasion. Methods: Fascin depletion was performed with lentiviral short hairpin RNA against fascin mRNA and stable cell line ($Fascin^{dep}$) was established. Matrigel-Transwell invasion and three-dimensional (3D) culture system were used to observe fascin depletion effects. In order to observe the changes of protease secretion by fascin depleted cancer cells, protease antibody array was performed. Results: Fascin was highly expressed in invasive cancer cells. Fascin-depleted cells showed decreased cancer invasion in Matrigel-Transwell invasion and 3D culture system. In addition, inhibition of proteases secreation and decrease of intracellular proteases mRNA expression were observed in fascin deplete cells. Conclusions: These results indicates that fascin is closely involved in proteases activity and cancer invasion. Therefore, fascin is a strategically important factor for controlling cancer invasion.

Muscular invasion by oral squamous cell carcinoma of the posterior mandibular alveolar ridge is associated with cervical lymph node metastasis

  • Min, Seung-Ki;Myoung, Hoon;Lee, Jong-Ho;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.42 no.3
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    • pp.133-138
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    • 2016
  • Objectives: To assess the association between muscle invasion by oral squamous cell carcinoma of the posterior mandibular alveolar ridge and cervical lymph node metastasis on the basis of preoperative magnetic resonance imaging (MRI). Materials and Methods: Twenty-six patients with oral squamous cell carcinoma of the posterior mandibular alveolar ridge were evaluated by MRI. The associations between cervical lymph node metastasis and independent factors evaluated by MRI were analyzed. Overall survival was also analyzed in this manner. Representative biopsy specimens were stained with anti-podoplanin and anti-CD34 antibodies. Results: Mylohyoid muscle invasion was associated with cervical lymph node metastasis. A combinational factor of mylohyoid and/or buccinator muscle invasion was also associated with cervical lymph node metastasis. Cervical lymph node metastasis and masticator space invasion had a negative effect on overall survival. No lymphatic vessels were identified near the tumor invasion front within the mandible. In contrast, lymphatic vessels were identified near the front of tumor invasion in the muscles. Conclusion: This study demonstrates an association between muscular invasion by oral squamous cell carcinoma of the posterior mandibular alveolar ridge and cervical lymph node metastasis.

Risk Factors of Microscopic Invasion in Early Gastric Cancer

  • Choi, Jong-Ho;Suh, Yun-Suhk;Park, Shin-Hoo;Kong, Seong-Ho;Lee, Hyuk-Joon;Kim, Woo Ho;Yang, Han-Kwang
    • Journal of Gastric Cancer
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    • v.17 no.4
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    • pp.331-341
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    • 2017
  • Purpose: This study aimed to evaluate the clinical significance of microscopic invasion to determine the adequate resection margin in early gastric cancer (EGC). Materials and Methods: A retrospective review was performed that included patients who underwent gastrectomy for clinical early gastric cancer (cEGC) at Seoul National University Hospital between January 2007 and December 2010. After subtracting the microscopic resection margin from the gross resection margin for each proximal or distal resection margin, microscopic invasion was represented by the larger value. Microscopic invasion and its risk factors were analyzed according to the clinicopathologic characteristics. Results: In total, 861 patients were enrolled in the study. Microscopic invasion of cEGC was $6.0{\pm}12.8mm$, and the proportion of patients with microscopic invasion ${\geq}0mm$ was 78.4%. In the risk group, tumor location, pT stage, and differentiation did not significantly discriminate the presence of microscopic invasion. The microscopic invasion of EGC-IIb was $13.9{\pm}16.8mm$, which was significantly greater than that of EGC-I. No linear correlation was observed between the overall tumor size and microscopic invasion (R=0.030). The independent risk factors for microscopic invasion ${\geq}20mm$ were EGC-IIb vs. EGC-I/IIa/IIc/III (odds ratio [OR], 3.103; 95% confidence interval [CI], 1.533-6.282; P=0.002) and male vs. female sex (OR, 1.655; 95% CI, 1.012-2.705; P=0.045). Conclusions: Male sex and EGC-IIb were independent risk factors for microscopic invasion ${\geq}20mm$. Examination of intraoperative frozen sections is highly recommended to avoid resection margin involvement, especially in cases of EGC-IIb.