Purpose: Accurate evaluation of cervical lymph node (LN) metastasis of head and neck squamous cell canter (SCC) is important to treatment planning. We evaluated the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of cervical LN metastasis of head and neck SCC and performed a retrospective comparison with CT/MRI findings. Materials & Methods: Seventeen patients with pathologically proven head and neck SCC underwent F-18 FDG PET/CT and CT/MRI within 4 week before surgery. We recorded lymph node metastases according to the neck level system of imaging-based nodal classification. F-18 FDG PET/CT images were analyzed visually for assessment of regional tracer uptake in LN. We analyzed the differences in sensitivity and specificity between F-18 FDG PET/CT and CT/MRI using the Chi-square test. Results: Among the 17 patients, a total of 123 LN levels were dissected, 29 of which showed metastatic involvement. The sensitivity and specificity of F-18 FDG PET/CT for detecting cervical LN metastasis on a level-by-level basis were 69% (20/29) and 99% (93/94). The sensitivity and specificity of CT/MRI were 62% (18/29) and 96% (90/94). There was no significant difference in diagnostic accuracy between F-18 FDG PET/CT and CT/MRI. Interestingly, F-18 FDG PET/CT detected double primary tumor (hepatocellular carcinoma) and rib metastasis, respectively. Conclusion: There was not statistically significant difference of diagnostic accuracy between F-18 FDG PET/CT and CT/MRI for the detection of cervical LN metastasis of head and neck SCC. The low sensitivity of F-18 FDG PET/CT was due to limited resolution for small metastatic deposits.
Hong, Young Seon;Park, Cho Hyun;Park, Jin-No;Lee, Kyung Shik;Kim, In Chul
IMMUNE NETWORK
/
v.1
no.1
/
pp.36-44
/
2001
Background : Peritoneal metastasis is one of the maj or types of the stomach cancer recurrence and the role of the adhesion molecules is thought to be very much important in this event. Retinoic acid (RA) has been known to induce the growth inhibition and differentiation of various malignancies, and apoptpsis and the change of expression of adhesion molecules have been reported to be involved in the action of RA. Methods : We studied the adhesion abilities of SNU-1, SNU-5, and SNU-6 cells to the peritoneal endothelial cells as well as the expression of the adhesion molecules (CD44, ICAM-1) in Western blot analysis. And also we studied the expression of apoptosis and the change of expression patterns of the various isoforms of CD44 and the change of the adhsion abilities of the cell line cells after RA treatment. Results: CD44 was expressed in SNU-5 and -16, together with an isoform in SNU-16. ICAM-1 was not expressed in any of the cell line cells tested. After the treatment of RA in the concentration range of $1-5{\times}10^{-5}M$ to three stomach cancer cell lines, growth inhibition, apoptosis and the change of expression of the CD44 were noted. After RA treatment, the expression of CD44H was weakly increased in SNU-1, and was markedly increased in SNU-5. In SNU-16, the expression of CD44H was decreased while that of CD44E were markedly increased. The adhesibility of cells to peritoneal cells was increased in relation with the increase of the CD44H expression, which shows the fact that the adhesibility of tumor cells to peritoneal mesothelial cells is mediated by CD44H recognizing hyaluronic acid. Conclusion : RA induces growth inhibition of stomach cancer cell line cells and increase the adhesiblity of stomach cancer cell line cells to peritoneal mesothelium. It is believed that RA decreases the metastatic ability of stomach cancer cells by upregulating the CD44H expression.
Kim, Jae Wha;Yoon, Sun Young;Joo, Joung-Hyuck;Kang, Ho Bum;Lee, Younghee;Choe, Yong-Kyung;Choe, In Seong
IMMUNE NETWORK
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v.2
no.3
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pp.175-181
/
2002
Background: S100A6 is a calcium-binding protein overexpressed in several tumor cell lines including melanoma with high metastatic activity and involved in various cellular processes such as cell division and differentiation. To detect S100A6 protein in patient' samples (ex, blood or tissue), it is essential to produce a monoclonal antibody specific to the protein. Methods: First, cDNA coding for ORF region of human S100A6 gene was amplified and cloned into the expression vector for GST fusion protein. We have produced recombinant S100A6 protein and subsequently, monoclonal antibodies to the protein. The specificity of anti-S100A6 monoclonal antibody was confirmed using recombinant S100A recombinant proteins of other S100A family (GST-S100A1, GST-S100A2 and GST-S100A4) and the cell lysates of several human cell lines. Also, to identify the specific recognition site of the monoclonal antibody, we have performed the immunoblot analysis with serially deleted S100A6 recombinant proteins. Results: GST-S100A6 recombinant protein was induced and purified. And then S100A6 protein excluding GST protein was obtained and monoclonal antibody to the protein was produced. Monoclonal antibody (K02C12-1; patent number, 330311) has no cross-reaction to several other S100 family proteins. It appears that anti-S100A6 monoclonal antibody reacts with the region containing the amino acid sequence from 46 to 61 of S100A6 protein. Conclusion: These data suggest that anti-S100A6 monoclonal antibody produced can be very useful in development of diagnostic system for S100A6 protein.
Purpose: The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and Methods: The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results: The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion: Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.
In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.
During the period of 4 years from August 1975 to August 1979 one hundred and forty seven cases of lung cancer were seen at Paik Foundation Hospital in Seoul, Korea. Among these 147 cases, 104 patients had primary carcinoma of the lung and the remainder was metastatic carcinoma to the lung. Among these 104 primary carcinoma patients, 73 cases were proven histologically as primary carcinoma of the lung. There were three cases of alveolar cell carcinoma [Table 1 ]. This clinical observation is based on those 73 cases including three case reports of the alveolar cell carcinoma. 1. Peak incidence was observed in the 5th decade of life. Male to female ratio was 2 to 1 [Fig. 1]. 2. Pathological classifications were as follows: epidermoid carcinoma, 24 cases [32.9%]; undifferentiated carcinoma, 20 cases [27.4%]; adenocarcinoma, 15 cases [20.5%]; bronchioloalveolar carcinoma [5.5%] and positive cytology, 10 cases [13.7%] [Fig. 2]. 3. Evidence of inoperability was observed in 55 patients [75% of the 73 cases] [Table 3]. 4. Among those 73 cases, operability was evaluated in 18 patients or 25%. One patient refused operation and 17 patients [23.6%] were explored. In 11 [15%] out of 17 patients, thoracotomies were performed. Six cases were pneumonectomies and 5 cases were lobectomies or bilobectomies [Fig. 3]. 5. First case of alveolar cell carcinoma was a 46 year-old housewife complaining of cough and hemoptysis for one year. The plain chest X-ray and bronchogram showed characteristic pictures as Figures 4 and 5. A pneumonectomy was carried out. Histologically, a beautiful alveolar carcinoma consisted of the characteristic tall columnar epithelial cells, which were lining the alveolar spaces as seen in Figures 6, 7, 8, and 20. 6. In the second case of 41 year old male, predominant clinical feature was single, well defined mass in the right lower lobe [Fig. 10 and 11] on chest X-ray. Bilobectomized specimen showed fragile, soft and hard tissue containing mucoid secretions and focal yellowish necrosis with pigmentation on cut surface [Fig. 12]. Slides showed tumor cells lined up along the alveolar septa with papillary projections [Fig. 13 and 14]. 7. Third case of alveolar cell carcinoma was a 50-year-old housewife with hemoptysis. An outstanding clinical picture was a round to lobulated mass in the right upper lobe [Fig. 16]. She is living now, 2 years and 1 month post-operatively, but has arrived at terminal stage with military nodular disseminations to the contralateral lung [Fig. 19].
Background: Cervical metastasis of unknown origin is defined as histologic evidence of malignancy in the cervical lymph nodes with no apparent primary site of origin for the metastatic tumor. Patients and Methods: A retrospective review of 20 cervical metastasis of unknown origin diagnosed and managed between january 1989 and December 1999 at the Korea University was undertaken to determine outcome. Patient age ranged 46 to 78 years (mean 60). There were 17 men and 3 women. The aim of this study is to ananlyze the diagnostic approach and the result of treatment of the cervical metastasis of unknown origin. Result: Histopathologically, squamous cell carcinoma (15 case, 75%) were the most common, followed by adenocarcinoma (4 case, 20%), undifferentiated carcinoma (1 case, 5%) According to the criteria of the AJCC on staging, N1 was 2 cases, N2a 2 cases, N2b 5 cases, N2c 1 cases, N3 10 cases. Overall survival rate for all patients at 2 years was 45% and 5 years 25%, and in the combination therapy(surgery and radiotherapy group (12 cases)) it was 67% and 34% respectively, high compared with other treatment modality such as surgery or radiotherapy alone. In extracapsular spread positive group, 5 year survival rate was 12%, but was 33% in the extracapsular spread negative group. Conclusion: With no stastatical significance, extracapsular spread group was poor outcome in our study. Combination of radiotherapy and surgery was more effective treatment result than surgery alone or radiotherapy alone in our study. But, overall prognosis of cervical metastasis of unknown origin was very poor despite aggressive treatment (5 year survival rate: 25%).
Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.
Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.
Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.
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