The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver Injury

BACKGROUND/AIMS: For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model. METHODS: A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold. Later, the ADSCs were cultured in hepatic differentiation medium for 2 weeks by a 3-step method. For in vivo experiments, Foxa2-overexpressing ADSCs were loaded in the scaffold, cultured in hepatic differentiation medium and later were implanted in the dorsa of nude mice subjected to acute liver injury (thioacetamide intraperitoneal injection). RESULTS: Foxa2-overexpressing ADSCs showed greater increases in hepatocyte-specific gene markers (alpha fetoprotein [AFP], cytokeratin 18 [CK18], and albumin), cytoplasmic glycogen storage, and cytochrome P450 expression than cells that underwent the conventional differentiation method. In vivo experiments using the nude mouse model showed that 2 weeks after scaffold implantation, the mRNA expression of AFP, CK18, dipeptidyl peptidase 4 (CD26), and connexin 32 (CX32) was higher in the Foxa2-overexpressing ADSCs group than in the ADSCs group. The Foxa2-overexpressing ADSCs scaffold treatment group showed attenuated liver injury without stem cell homing in the thioacetamide-induced acute liver injury model. CONCLUSIONS: Foxa2-overexpressing ADSCs applied in a scaffold system enhanced hepatocyte-like differentiation and attenuated acute liver damage in an acute liver injury model without homing effects.

Heparin/Collagen 3D Scaffold Accelerates Hepatocyte Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells

Both mature and stem cell-derived hepatocytes lost their phenotype and functionality under conventional culture conditions. However, the 3D scaffolds containing the main extracellular matrix constitutions, such as heparin, may provide appropriate microenvironment for hepatocytes to be functional. The current study aimed to investigate the efficacy of the differentiation capability of hepatocytes derived from human Wharton's jelly mesenchymal stem cells (WJ-MSCs) in 3D heparinized scaffold. In this case, the human WJ-MSCs were cultured on the heparinized and non-heparinized 2D collagen gels or within 3D scaffolds in the presence of hepatogenic medium. Immunostaining was performed for anti-alpha fetoprotein, cytokeratin-18 and -19 antibodies. RT-PCR was performed for detection of hepatic nuclear factor-4 (HNF-4), albumin, cytokeratin-18 and -19, glucose-6-phosphatase (G6P), c-met and Cyp2B. The results indicated that hepatogenic media induced the cells to express early liver-specific markers including HNF4, albumin, cytokeratin-18 and 19 in all conditions. The cells cultured on both heparinized culture conditions expressed late liver-specific markers such as G6P and Cyp2B as well. Besides, the hepatocytes differentiated in 3D heparinized scaffolds stored more glycogen that indicated they were more functional. Non-heparinized 2D gel was the superior condition for cholangiocyte differentiation as indicated by higher levels of cytokeratin 19 expression. In conclusion, the heparinized 3D scaffolds provided a microenvironment to mimic Disse space. Therefore, 3D heparinized collagen scaffold can be suggested as a good vehicle for hepatocyte differentiation.

Factors Affecting Prognosis of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Implications for Future Therapeutic Strategies

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) exhibits poor prognosis. The aim of this study is to evaluate factors associated with survival of HCC patients with PVTT to suggest better therapeutic options. METHODS: Patients with HCC which were newly diagnosed at three tertiary hospitals between January 2004 and December 2012, were reviewed retrospectively. Among them, Barcelona Clinic of Liver Cancer stage C patients with PVTT were identified. Factors affecting overall survival (OS) were analyzed and efficacies of the treatment modalities were compared. RESULTS: Four hundred sixty five patients with HCC and PVTT were included. Liver function, tumor burden, presence of extrahepatic tumor, alfa fetoprotein, and treatment modalities were significant factors associated with OS. Treatment outcomes were different according to the initial modalities. OS of the patients who received hepatic resection, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), sorafenib, systemic cytotoxic chemotherapy, radiation therapy (without combination), and supportive care were 27.8, 7.1, 6.7, 5.3, 2.5, 3.0, 1.8, and 0.9 months, respectively (P<0.001). Curative-intent treatments such as hepatic resection or RFA were superior to noncurativeintent treatments (P<0.001). TACE or HAIC was superior to sorafenib or systemic chemotherapy (P<0.001). Combining radiotherapy to TACE or HAIC did not provide additional benefit on OS (P=0.096). CONCLUSIONS: Treatment modalities as well as baseline factors significantly influenced on OS of HCC patients with PVTT. Whenever possible, curative intent treatments should be preferentially considered. If unable, locoregional therapy would be a better choice than systemic therapy in HCC patients with PVTT.

Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis of allergic asthma / 中南大学学报(医学版)

OBJECTIVE@#To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide (ANP), and to analyze the potential role of ANP signaling in the pathogenesis of asthma.
@*METHODS@#We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-γ and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of natriuretic peptide receptor A (NPRA), transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot.
@*RESULTS@#The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell (PBMC) from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively (P<0.05). Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency (P<0.05). In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-γ/IL-4 (r=-0.85, P<0.05; r=-0.88, P<0.05, respectively).
@*CONCLUSION@#Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.

Construction of plasmid vector pAFP-HSVtk-IRES2-EGFP and its effect on the cytotoxicity of ganciclovir to hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Herpes simplex virus thymidine kinase phosphorylates ganciclovir to ganciclovir monophosphate, which is then converted to ganciclovir triphosphate by endogenous cellular nucleoside kinases. The ganciclovir triphosphate acts as a DNA chain terminator due to the lack of a functional 3'-OH group and terminates the process of DNA replication, hence leading to cell apoptosis. At present, HSVtk gene usually acts as suicide gene to kill tumor cells. The aim of this study was to investigate the selective cytotoxicity of the herpes simplex virus thymidine kinase/ganciclovir (HSVtK/GCV) suicide gene system controlled by the a-fetoprotein (AFP) promoter on hepatocellular carcinoma (HCC) cells in vitro.</p><p><b>METHODS</b>pAFP-HSVtk-IRES2-EGFP recombinant plasmid vectors driven by the AFP promoter were constructed. HL-7702 liver cells, HUH-7 HCC, and HepG2 HCC were transfected with the recombinant plasmids. HSVtK gene expression was detected using Western blotting analysis. HepG2 cells line stably expressing HSVtk gene was selected by G418 reagent. The cytotoxicity of HSVtK/GCV suicide gene system on hepatoma cells was measured by CCK-8 reagents when different doses of ganciclovir were added.</p><p><b>RESULTS</b>Plasmid pAFP-TK-IRES2-EGFP-expressed HSVtk gene was constructed successfully. HSVtk gene expression level was significantly higher in AFP-positive hepatoma cells than in AFP-negative liver cells. After G418 selection, a HepG2 cells line stably expressing HSVtk gene was acquired. With the increase of the dose of ganciclovir the optical density at 450 nm of HepG2 cells stably expressing HSVtk gene gradually decreased (P < 0.05).</p><p><b>CONCLUSION</b>The HSVtK gene-specific expression in hepatoma cells as well as the cytotoxicity of the suicide gene system in HepG2 cells provided the basis for the targeted gene therapy of HCC.</p>

Expressão imunoistoquímica de diferenciação e crescimento celular em cardiomiócitos de neonatos / Immunohistochemical expression of cell differentiation and growth in neonate cardiomyocytes

FUNDAMENTO: As alterações cardíacas na fase de transição do coração fetal para a vida extrauterina vêm sendo exploradas por inúmeras pesquisas em animais, e os mecanismos celulares responsáveis por essas modificações ainda não estão bem documentado em seres humanos. OBJETIVO: Avaliar o mecanismo de diferenciação celular em cardiomiócitos ocorridas nos primeiros dias de vida, por meio da análise imunoistoquímica de proteínas envolvidas com processos de proliferação e contração muscular, em amostras de miocárdio de recém-natos humanos. MÉTODO: Estudo transversal de amostras parafinadas de miocárdio provenientes de banco de necropsias de recémnascidos humanos, divididos em dois grupos amostrais: recém-nascidos a termo que foram a óbito com no máximo dois dias de vida (NEO1) com 10 casos, e recém- nascidos a termo que foram a óbito entre três e 10 dias de vida (NEO2) com 14 casos, a fim de seguir uma linha de tempo que contemplasse a fase de transição da circulação fetal a vida extrauterina. As amostras foram estudadas em tissue microarray e os anticorpos utilizados foram o Ki67, PCNA, PTEN, Bcl2 (proliferação) e HHF35 e actina sarcomérica (proteínas contráteis). RESULTADOS: Foi encontrada diferença com o Ki67 p = 0,02, HHF35 p < 0,01 e actina sarcomérica p = 0,02, e a expressão do Ki67 foi mais alta no grupo NEO1 e a expressão do HHF35 e da actina sarcomérica foi mais alta no grupo NEO2. CONCLUSÃO: Os resultados sugerem que os cardiomiócitos apresentam uma característica proliferativa (Ki67) nos NEO1 e que essa vai, seguindo uma linha temporal, sendo substituída por um caráter de diferenciação (HHF35 e actina sarcomérica) nos NEO2.

BACKGROUND: The cardiac alterations during the fetal heart transition to extrauterine life have been explored by several animal studies and the cell mechanisms responsible for these modifications are not well documented in humans. OBJECTIVE: To evaluate the mechanism of cell differentiation into cardiomyocytes that occur in the first days of life, through immunohistochemical analysis of proteins involved in proliferation and muscle contraction processes, in samples of human neonate myocardium. METHODS: Cross-sectional study of paraffin-sample sections of myocardium from an autopsy database of human neonates, divided into two sample groups: full-term neonates who died after a maximum of two days of life (NEO1) with 10 cases, and full-term infants who died between 3 and 10 days of life (NEO2) with 14 cases, in order to follow a temporal line that would contemplate the transition from fetal circulation to extrauterine life. The samples were studied in tissue microarray and the antibodies used were Ki67, PCNA, PTEN, Bcl2 (proliferation), HHF35 and sarcomeric actin (contractile proteins). RESULTS: Difference was observed regarding Ki67, p = 0.02; HHF35, p <0.01 and sarcomeric actin, p = 0.02, with Ki67 expression being higher in NEO1 group, whereas HHF35 and sarcomeric actin expression was higher in the NEO2 group. CONCLUSION: The results suggest that cardiomyocytes have a proliferation characteristic (Ki67) in NEO1 which, following a temporal line, will be replaced by a differentiation characteristic (HHF35 and sarcomeric actin) in NEO2.

A modified method to isolate and identify the adult mesenchymal stem cells from human bone marrow / 中国实验血液学杂志

The study was aimed to establish a protocol of isolating and culturing adult mesenchymal stem cells (MSC) from human bone marrow aspirate and identify them by surface antigen analysis and committed differentiation in order to provide an experimental foundation for achieving a therapeutic benefit in applying MSC in hematopoietic stem cell transplantation. MSCs were obtained from fresh human bone marrow aspirate by gradient centrifugation with Percoll (1.073 g/ml) and anchoring culture in L-DMEM with 10% fetal bovine serum by a full medium exchange every 3 days. The MSC surface antigens, including CD34, CD45, CD73, CD105, CD166, were analyzed on FACScan flow cytometer. Under culture in conditioned medium for osteogenesis (the hormone cocktail containing 0.1 micromol/L dexamethasone, 10 mmol/L glycerol-2-phosphate and 50 micromol/L ascorbic acid) and adipogenesis (the cocktail containing 1 micromol/L dexamethasone, 5 mg/L insulin, 0.5 mmol/L 1-methyl-3-isobutylxanthine and 60 micromol/L indomethacin), MSCs committedly differentiated into osteoblasts and adipocytes. The differentiated mesenchymal stem cells were identified by morphological observation and immunohistochemical staining. The results showed that by gradient centrifugation and adhesion culture, MSCs could be isolated and culture-expanded from human bone marrow aspirate. These cells were uniformly negative for CD34, CD45 and positive for CD73, CD105 and CD166. The osteogenic differentiated cells were positive for alkaline phosphatase (ALP) and the adipogenic differentiated cells displayed accumulation of lipid vacuoles, as detected by oil red O. It is concluded that MSC can be isolated and expand-cultured from adult human bone marrow aspirate and committedly differentiate into osteoblasts and adipocytes. MSC primary identification can be accomplished by flow cytometry and induced differentiation. The set of methods in current experiment shows somewhat practical value for basic research and clinical application.

El antígeno carcinoembrionario: a propósito de un viejo conocido / The carcinoembryonic antigen: by the way a well-known friend

The carcinoembryonic antigen (CEA) is glycoprotein localized in the apical surface of mature enterocytes. The members of the CEA gene family are clustered on chromosome 19q13.2. It is formed by 29 genes, of which 18 are expressed. Many functions of CEA have been known in healthy individuals, however its role as cell adhesion molecule is the most studied. Besides the colon, CEA is expressed in the stomach, tongue, oesophagus, cervix, and prostate. The most important clinical function is in colorectal, gastric and ovary cancer. It is used as prognosis marker, staging system, recurrence, treatment response and liver metastases. There are many no neoplasic-diseases that enhance CEA value. Actually, the CEA is being studying as target of immunotherapy.

El antígeno carcinoembrionario (ACE) es una glucoproteína localizada en el polo apical de los enterocitos. Los genes que codifican para el ACE se localizan en el cromosoma 19q13.2. El grupo total está constituido por 29 genes, divididos en tres subgrupos de los cuales se expresan sólo 18. En el individuo sano existen múltiples funciones del ACE que han sido ampliamente estudiadas, su función como molécula de adhesión ha sido la más ampliamente difundida. En pacientes sanos además de expresarse a nivel de colon el ACE se expresa en células de la lengua, esófago, estómago, cervix y próstata. Los pacientes que reciben una mayor utilidad clínica son aquellos con cáncer colorrectal (CCR), cáncer gástrico y cáncer de ovario. Su uso más amplio es en el CCR, actualmente se utiliza como marcador pronóstico, estadiaje, marcador de recurrencia, de respuesta al tratamiento y como indicador de metástasis a nivel hepático. Existen algunas patologías no neoplásicas que causan elevación de las cifras séricas de ACE. Actualmente se estudia al ACE como blanco de inmunoterapia dirigida a tumores que contengan células que expresen esta molécula.

Structural features of GR6 gene and its expression in colorectal neoplasm / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine the characteristics of GR6 gene and putative GR6 protein, and to evaluate the expression of GR6 gene in colorectal cancer and normal mucosa.</p><p><b>METHODS</b>Bioinformatic software and databases were applied to analyze the characteristics of GR6 gene and putative GR6 protein. Semi-quantitative RT-PCR was used to detect the expression of GR6 gene in colorectal carcinoma, adenoma and normal mucosa.</p><p><b>RESULT</b>GR6 gene, encoding putative GR6 protein, consisted of 3 exons and contained 4 CpG islands by sequence analysis. It was predicted that putative GR6 protein included one protein kinase C phosphorylation site, one casein kinase II phosphorylation site, and three N-myristoylation sites. PSORT II software analysis predicted that putative GR6 protein was located in nucleus (reliability: 76.7%). At the level of mRNA, the expression of GR6 gene was high in normal mucosa, moderate in mucosa adjacent to cancer and adenoma tissue, low in colorectal carcinoma tissue. Significant differences were demonstrated between normal mucosa and adenoma (P<0.05), normal mucosa and carcinoma (P<0.01).</p><p><b>CONCLUSION</b>The putative GR6 protein, encoded by GR6 gene may predictably function as an important nuclear signal transduction molecule. Decreased expression of GR6 gene may play an important role in the initiation and promotion of colorectal neoplasia.</p>

Prognostic Value of Preoperative Serum Alpha- Fetoprotein Level in Resectable Gastric Cancer

PURPOSE: Alpha-fetoprotein (AFP) is widely accepted as a useful tumor marker for diagnosis of hepatocellular carcinomas. On rare occasions, however, an abnormal elevation of serum AFP also has been reported in an adenocarcinoma of the gastrointestinal tract. We evaluated the influence of preoperative abnormal elevation of serum AFP (AFP positivity) on the prognosis of resectable gastric cancers. MATENRIALS AND METHODS: 812 gastric cancer patients, who were investigated for serum AFP before their operations and who underwent gastric resections with D2 or more extended lymph node dissection, were enrolled in the study. The survival rates were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Fifty patients (6.2%) were AFP positive (10.1~4322.6 ng/ml). The survival rate of the AFP positive group was significantly lower than that of the AFP negative group ( 46.6% vs. 67.0%; P=0.0002). The depth of tumor invasion, the degree of regional lymph node metastasis, distant metastases, the TNM stage, the gross type, differentiation, the extent of gastric resection, and the curability of the surgery also significantly influenced survival. Multivariate analysis revealed that the depth of tumor invasion, the degree of regional lymph node metastasis, the curability of the surgery, and AFP positivity were independent prognostic indicators. CONCLUSION: Preoperative serum AFP can be used as an independent prognostic factor of resectable gastric cancer.

Skeletal ossification of 20-day albino rat fetuses under the influence of maternal protein malnutrition and low doses caffeine administration during pregnancy

The purpose of the present work was to study skeletal ossification of the 20-day albino rat fetus under the influence of maternal protein malnutrition and the administration of low subtoxic doses of caffeine which are known to produce minimal effects on the fetus. Twenty-four pregnant albino rats were divided equally into 4 groups; control group [20% protein], caffeine group [20% protein + caffeine], protein malnourished group [6% protein] and combined group [6% protein + caffeine]. Maternal protein malnutrition started from the first day of gestation, while low dose caffeine [25 mg/kg BW, IG] was given daily to the mothers from day 6-12 of gestation. Fetuses were collected by caesarian section at the 20th day of gestation. Bones were stained by alizarin red using Dawson's then ossification was assessed. The results revealed that low doses of caffeine administration have mild effects on ossification of fetal bones, while maternal protein malnutrition delayed ossification markedly. The combination of caffeine and protein malnutrition increased the delaying of ossification in the combined of caffeine and protein malnutrition increased the delaying of ossification in the combined group as compared to all other studied group. A significant delay in ossification was especially noticed in sternum, cervical and sacral vertebrae, pubis and metacarpal bones of the fetuses of the combined group as compared to the caffeine group which indicates that caffeine has a synergistic role to protein malnutrition in the combined group

Hepatocellular Carcinoma after Radiofrequency Ablation: Recurrent Pattern and Influenting Factor

PURPOSE: To evaluate patterns of recurrence and factors which influence them in radiofreqency (RF) ablation for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between May 1999 and March 2000, 69 patients with 82 HCCs underwent RF ablation for complete necrosis. They were diagnosed by tissue biopsy or tumor marker, and the results of triphasic spiral CT. The indications were that nodular lesions were clearly visualized at sonography, less than 5 cm in size and less than four in number, and that patients had no history of previous treatment. Local therapeutic efficacy such as complete necrosis and marginal recurrence, and new lesions were evaluated by means of triphasic spiral CT performed at least six months after the completion of ablation. We then analyzed the correlation between local therapeutic efficacy and various influential factors such as tumor size, whether the tumor was attached to the portal vein, gross morphology, Child-Pugh classification, and alpha- fetoprotein level before the procedure, as well as the correlation between new lesions and influential factors which included the alpha-fetoprotein level before the procedure, Child-Pugh classification, and multiplicity per person. RESULTS: During a mean follow-up period of 8.95 (range, 6-14) months after RF ablation, the rate of complete necrosis and of marginal recurrence was 91% and 12%, respectively. When a tumor was larger and was attached to a large branch of the portal vien, the incidence of incomplete necrosis and marginal recurrence was greater. The occurrence rate of new lesion was 19.4%. When the alpha-fetoprotien level before the procedure was higher and a tumor was multiple in number, new lesions occurred more frequently. CONCLUSION: Sufficient knowledge of patterns of recurrence and the factors which influence them might improve the therapeutic effects of RF ablation in patients with HCC.

Cytokeratin expression in human fetal tongue and buccal mucosa.

Expression of cytokeratins (CK), a subset of intermediate filament (IF) proteins in epithelia, is developmentally regulated. CK expression may also change after malignant transformation. Our earlier studies on CK expression in human oral tumours and pre-cancerous lesions have shown specific changes in CK expression. We analysed CK expression in human tongue and buccal mucosa (BM) in fetuses in the embryonic age group of 16 to 27 weeks using biochemical and immunohistochemical techniques to find out whether there is any similarity in CK expression in human oral squamous cell carcinomas (SCC) and fetal oral tissues. CK 1, 8 and 18 were detected in a majority of samples using both techniques. Our earlier studies had shown aberrant expression of CK 1 and 18 in many of the oral SCC and leukoplakias. Studies by immunohistochemistry showed that these different CK antigens were expressed in different cell layers. CK 1(2) were present in the stratified epithelial layers whereas CK 8 and 18 were restricted to glandular epithelium. Till 27 weeks of gestation, both tongue and BM expressed CK 1, 8 and 18 along with CK 6 and 16. Thus, fetal tissues showed some similarities in CK pattern with their respective SCC.

The Evaluation of Domestic Immunoradiometric Assay Kit for Alpha-fetoprotein / 대한핵의학회잡지

PURPOSE: Although alpha-fetoprotein is one of the most commonly used tumor markers in Korea, most of the radioimmunoassay kits for alpha-fetoprotein have been imported from foreign countries. The purpose of this study was to evaluate the performance of a recently developed domestic immunoradiometric kit for alpha- fetoprotein (Riakey AFP IRMA CTR, Sin-Jin Medics, Seoul, Korea). MATERALS AND METHODS: We evaluated intra- and inter-assay precision, recovery rate, parallelism, and sensitivity of serum alpha-fetoprotein measurement using Riakey AFP IRMA CTR kit. The values of alpha-fetoprotein measured by Riakey AFP IRMA CTR kit were compared with those measured by two foreign commercial kits (alpha-fetoproteina of Radim and alpha-feto.riabead of Abbott). RESULTS: Intra-assay coefficients of variation on three different levels were 5.3% for 18.9 ng/ml, 3.4% for 133 ng/ml and 1.6% for 330 ng/ml. Inter-assay coefficients of variation were 9.7% for 20.9 ng/ml, 3.2% for 137 ng/ml and 4.1% for 330 ng/ml respectively. Recovery rate tests on all three different levels showed within 100+/-10%. Parallelism was also good and the sensitivity was 0.63 ng/ml. There was strong correlation between the measurement of alpha-fetoprotein by Riakey AFP IRMA CTR and that by two foreign commercial kits(r=0.98). CONCLUSION: The first Korean domestic immunoradiometric kit for alpha-fetoprotein, Riakey AFP IRMA CTR, performed well for clinical use.

Effectiveness of Diagnogstic Tools for The Detection of Recurrence after Curative Resection of Hepatocellular Carcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: In spite of improved diagnostic and therapeutic methods, the prognosis of hepatocarcinoma( HCC) is still poor because of the high recurrence rate. Early detection and active treatment of recurrent HCC are important to improve the survival. The objective of this study is to compare the effectiveness of diagnostic tools for early detection of the recurrence of HCC. METHODS: We retrospectively studied 236 patients who underwent curative hepatic resection for HCC at SNUH between 1993 and 1995. Postoperatively, we checked radiologic studies every three months and serum alpha- fetoprotein level monthly first, then every three months to detect recurrence. The patients were divided into four group (Low-Low;L-L, Low-High;L-H, High-Low;H-L, High-High;H-H) according to the serum levels of pre- and post-operative(3 months) alpha-fetoprotein levels (Low ; 20ng/ml). RESULTS: Overall recurrence rate was 55.1%. The recurrence rates in L-L gr., L-H gr, H-L gr., and H-H gr were 40.7%, 75.0%, 42.9% and 91.8% respectively. Increasing levels of alpha-fetoprotein at the time of dectection of recurrence were found in 13.6%, 66.7%, 25.9% and 92.9%, respectively(p<0.05). The 3- year disease-free survival rates are 62.1%, 25.0%, 57.8% and 6.3%, respectively(p<0.05). The 3-year overall survival rates are 79.2%, 50.0%, 83.6% and 51.1%, respectively(p<0.05). The detection rates of ultrasonography(US) and computed tomograpy(CT) were 82.4% and 97.2% respectively. Seven patients had lung metastasis on chest X-ray and two bone metastasis on bone scan, two spinal metastasis on spine X-ray and MRI and 2 adrenal metastasis by US and CT were detected. CONCLUSION: The patients who have high serum levels of alpha-fetoprotein postoperatively have a tendency to recur early. On the other hand, patients who have low serum levels of alpha-fetoprotein postoperatively recur late, usually without its elevation. Therefore, in former cases, early recurrence or remnant tumor should be suspected and in latter cases, regular US and/or CT is a more useful method for early detection of recurrent HCC than frequent checking of serum alpha-fetoprotein.

Alpha-Fetoprotein-Producing Carcinoma of the Gallbladder: A case report

We experienced a case of a gallbladder carcinoma detected incidentally by elevated serum alpha- fetoprotein. The patient had a symptom of mild intermittent indigestion, and a routine medical examination revealed elevation of serum alpha-fetoprotein. A mass, 4 cm 3 cm, was located in the gallbladder and it had not infiltrated the liver. The serum level of alpha-fetoprotein decreased after a cholecystectomy. The gallbladder mass was an adenocarcinoma of hepatoid differentiation. Cytoplasms of the tumor cells had positive reactivity to immunohistochemical staining of alpha-fetoprotein. In the course of postoperative follow up, the serum alpha-fetoprotein level increased continuously, and abdominal CT scanning proved multiple intrahepatic metastases.

Immunohistochemical Expression of CD34 and Vascular Endothelial Growth Factor in Hepatocellular Carcinoma / 대한암학회지

PURPOSE: Angiogenesis plays an important role in progression, invasion and metastasis of solid tumors. The Vascular Endothelial Growth Factor (VEGF) is thought to be a selective mitogen for endothelial cells. Hepatocellular carcinoma is a typical hypervascular tumor. However, the relationship between angiogenesis and angiogenic factor in hepatocellular carcinoma has not been evaluated. We investigated the relationship between microvessel density (MVD) and expression of VEGF in hepatocellular carcinoma. MATERIALS AND METHODS: Immunohistochemlcal staining, using anti-CD34 and anti-VEGF antibodies, was applied in 32 cases of hepatocellular carcinoma. Also, relationship between these neovascular factors (MVD and VEGF expression) and clinicopathologic parameters such as tumor size, bistologic grade, alpha-fetoprotein level, hepatitis B virus surface antigen, presence of cirrhosis and survival was evaluated. RESULTS: CD34 was reactive throughout the neoplastic tissue, albeit it was confined to a few periportal sinusoids and vessels in fibrous septa of adjacent cirrhotic liver. MVD was 59.6+22.7 and 44.3+21.5 in hepatocellular carcinoma and cirrhosis, respectively. VEGF was expressed in 9 cases (28.1%) of hepatocellular carcinoma, which was localized to the cytoplasm. MVD and VEGF expression was not significantly correlated (P>0.05). MVD was correlated with presence of cirrhosis and inversely conelated with alpha- fetoprotein level (p0.05). Expression of VEGF was not correlated with all clinicopathologic parameters (P>0.05). CONCLUSION: These results indicate that MVD in hepatocellular carcinoma is not directly correlated with VEGF expression, and suggest that other angiogenic factor may be involved in neovascularization of hepatocellular carcinoma. However, CD34 expression is closely associated with neovascular process in cirrhosis and hepatocelluar carcinoma.

Polyvesicular Vitelline Tumor of the Ovary: A case report

Polyvesicular vitelline tumor of the ovary is an extremely rare variant of yolk sac tumor. We present a case of pure polyvesicular vitelline tumor in a 43-year-old woman. Light microscopy revealed a predominantly polyvesicular pattern embedded in mesoblastic stroma with the cysts showing two type of lining; tall columnar and cuboidal, or mesothelioid cells. The lining atypical cells showed occasional mitoses and intracytoplasmic PAS positive hyaline globules. In some areas, the cystic space contained a large amount of intraluminal hyaline material. Immunohistochemically, alpha- fetoprotein and alpha-1-antitrypsin were detected as a fine granular deposit in the cytoplasm of epithelial cells and hyaline globules. Electron microscopically, marked specialization of the vesicular lining cells suggested a differentiation toward gut structures and mature yolk sac.

Polyvesicular Vitelline Tumor of the Ovary: A case report

Polyvesicular vitelline tumor of the ovary is an extremely rare variant of yolk sac tumor. We present a case of pure polyvesicular vitelline tumor in a 43-year-old woman. Light microscopy revealed a predominantly polyvesicular pattern embedded in mesoblastic stroma with the cysts showing two type of lining; tall columnar and cuboidal, or mesothelioid cells. The lining atypical cells showed occasional mitoses and intracytoplasmic PAS positive hyaline globules. In some areas, the cystic space contained a large amount of intraluminal hyaline material. Immunohistochemically, alpha- fetoprotein and alpha-1-antitrypsin were detected as a fine granular deposit in the cytoplasm of epithelial cells and hyaline globules. Electron microscopically, marked specialization of the vesicular lining cells suggested a differentiation toward gut structures and mature yolk sac.

A Case of a Primary Gastric Choriocarcinoma Diagnosed by Endoscopic Biopsy / 대한소화기내시경학회지

A case of primary choriocarcinoma in the stomach of a 60-year-old male is herein presented. The tumor was diagnosed as a choriocarcinoma by histologic examination and the immunohistochemical method of endoscopic biopsy of a specimen. Serum alpha- fetoprotein and beta-human chorionic gonadotropin were found to be significantly elevated. Multiple distant metastasis of the liver, intraabdominal lymph nodes and malignant ascites were also discovered. The high alpha-fetoprotein level in the serum might have been due to the coexistence of embryonal cell carcinoma or hepatoid adenocarcinoma or both in the stomach.