2.Methylmalonic acid in amniotic fluid and maternal urine as a marker for neural tube defects.
Xiaoping, LUO ; Lian, ZHANG ; Hong, WEI ; Wanjun, LIU ; Muti, WANG ; Qin, NING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2004;24(2):166-9
To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.
Amniotic Fluid/*chemistry
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Biological Markers/analysis
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Biological Markers/urine
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Folic Acid/blood
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Methylmalonic Acid/analysis
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Methylmalonic Acid/*urine
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Neural Tube Defects/*diagnosis
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Neural Tube Defects/metabolism
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Pregnancy Trimester, Second
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*Prenatal Diagnosis
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Vitamin B 12/blood
3.Gene Expression Profiling using Oligonucleotide Microarray in Atrophic Gastritis and Intestinal Metaplasia.
Kyong Rae KIM ; Soo Youn OH ; Ung Chae PARK ; Joon Ho WANG ; Jae Dong LEE ; Hyuk Jung KWEON ; Sang Yoon KIM ; Seung Hwa PARK ; Dong Kug CHOI ; Chan Gil KIM ; Seongc Ho CHOI
The Korean Journal of Gastroenterology 2007;49(4):209-224
BACKGROUND/AIMS: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach. METHODS: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization. RESULTS: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern. CONCLUSIONS: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.
Down-Regulation
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Gastritis, Atrophic/*genetics/metabolism
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Gene Expression Profiling
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Humans
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Intestines/*metabolism/*pathology
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Metaplasia/genetics/metabolism
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Microarray Analysis
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Tumor Markers, Biological/genetics/metabolism
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Up-Regulation
4.Prognostic Value of VEGF in Human Pancreatic Ductal Adenocarcinoma.
Yun Jeong LIM ; Jong Kyun LEE ; Cheol Keun PARK ; Sang Yong SONG ; Woo Young JANG ; Hye Young HA ; Dong Il PARK ; Kyu Taek LEE ; Seung Woon PAIK ; Byung Chul YOO ; Jong Chul RHEE
The Korean Journal of Internal Medicine 2004;19(1):10-14
BACKGROUND: Since pancreatic cancer metastasizes early regardless of the size of the primary tumor, it is suggested that angiogenic factor is upregulated in this disease. Among the angiogenic factors, vascular endothelial growth factor (VEGF) is the most potent and specific growth factor. The aim of this study is to elucidate the prognostic value of VEGF expression in pancreatic cancers. METHODS: We analyzed the VEGF expression using immunohistochemistry in 72 resected pancreatic ductal adenocarcinomas. We examined the prognostic value of the VEGF expression along with its relationship with the clinicopathological features. RESULTS: VEGF expression and mutant p53 expression were not associated with microvessel density. VEGF expression was positively associated with mutant p53 expression. There were no statistically significant relationships between the VEGF expression and other clinicopathological features, such as age, sex, CA19-9, tumor size, location, tumor differentiation, and stage. VEGF expression was not associated with patient survival. CONCLUSION: VEGF expression was not associated with the microvessel density and patient survival in pancreatic ductal adenocarcinoma.
Adolescent
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Adult
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Aged
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Biological Markers
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Carcinoma, Pancreatic Ductal/*metabolism/surgery
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Female
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Human
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Immunohistochemistry
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Male
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Middle Aged
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Pancreatic Neoplasms/*metabolism/surgery
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Prognosis
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Survival Analysis
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Vascular Endothelial Growth Factor A/*metabolism
5.Expression of Cdx2 Protein in Colorectal Cancer.
Jong Hae PACK ; Tae Dong KIM ; Heun Ah OH ; Eun Joo LEE ; Jun Whan KIM ; Byung Ik JANG ; Tae Nyeun KIM ; Moon Kwan JUNG ; Young Kyung BAE
The Korean Journal of Gastroenterology 2005;46(3):204-210
BACKGROUND/AIMS: The caudal-related homeobox transcription factor, Cdx2, plays an important role in proliferation and differentiation of intestinal epithelial cells. Its expression is confined to normal and neoplastic intestinal epithelium. We evaluated Cdx2 expression in advanced colorectal cancers to determine the correlation between Cdx2 expression and clinicopathologic characteristics. METHODS: Four hundreds twenty consecutive colorectal cancers were included in the study. Cdx2 expression was investigated by immunohistochemistry using tissue microarrays constructed from surgically resected specimens. 145 invasive breast cancers, normal tissues from gastric mucosa, liver, lung, kidney and ovary were used as control. Nuclear staining was considered to be positive and the result was divided into 3 categories. RESULTS: In the colorectal cancers, Cdx2 was expressed in 380 of 420 (90.5%) cases, and 349 of 380 (83%) cases showed strong and diffuse staining and 31 of 420 (7.5%) cases showed weakly positive staining. Forty patients (9.5%) of colorectal cancer were negative for Cdx2. All of the invasive breast cancers and all non-neoplastic control tissues except the regions of intestinal metaplasia in gastric mucosa, which showed strong Cdx2 expression, were negative for Cdx2. Loss of Cdx2 expression was observed more frequently in cases with deeper invasion (p<0.05), lymph node metastasis (p<0.05), poor histologic differentiation (p<0.001), and distant metastasis (p<0.05). CONCLUSIONS: Cdx2 could be a highly sensitive marker to detect metastasis from intestine and might be useful as a novel prognostic marker in colorectal cancers.
Adult
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Aged
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Aged, 80 and over
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Colorectal Neoplasms/*metabolism/pathology
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Female
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Homeodomain Proteins/*metabolism
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Humans
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Immunohistochemistry
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Male
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Middle Aged
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Tumor Markers, Biological/analysis
6.Comparison of 1.5T and 3T 1H MR Spectroscopy for Human Brain Tumors.
Ji hoon KIM ; Kee Hyun CHANG ; Dong Gyu NA ; In Chan SONG ; Seung Ja KIM ; Bae Ju KWON ; Moon Hee HAN
Korean Journal of Radiology 2006;7(3):156-161
OBJECTIVE: We wanted to estimate the practical improvements of 3T proton MR spectroscopy (1H MRS) as compared with 1.5T 1H MRS for the evaluation of human brain tumors. MATERIALS AND METHODS: Single voxel 1H MRS was performed at both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data acquisition parameters at both field strengths, the 1H MRS spectra were obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec) with the voxel size ranging from 2.0 cm3 to 8.7 cm3. The signal to noise ratios (SNRs) of the metabolites (myoinositol (MI), choline compounds (Cho), creatine /phosphocreatine (Cr), N-acetyl-aspartate (NAA), lipid and lactate (LL)) and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at both TEs between the two field strengths in each brain tumor. The degrees of spectral resolution between the Cho and Cr peaks were qualitatively compared between the two field strengths in each brain tumor. RESULTS: The SNRs of the metabolites at 3T demonstrated 49-73% increase at a short TE (p < 0.01) and only 2-12% increase at an intermediate TE (p > 0.05) compared with those of 1.5T. The SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer inversion at 3T (p < 0.05). There was no significant difference in the metabolite ratios between the two field strengths. The degrees of the spectral resolution at 3T were slightly superior to those of 1.5T at a short TE. CONCLUSION: As compared with 1.5T, 3T 1H MRS demonstrated 49-73% SNR increase in the cerebral metabolites and slightly superior spectral resolution only at a short TE, but little at an intermediate TE, in the brain tumors. There was no significant difference in the metabolite ratios between the two field strengths.
Sensitivity and Specificity
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Reproducibility of Results
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Protons/*diagnostic use
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Middle Aged
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Male
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Magnetic Resonance Spectroscopy/*methods
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Humans
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Female
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Brain Neoplasms/*diagnosis/*metabolism
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Biological Markers/*analysis
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Aged
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Adult
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Adolescent
7.Biological Profiles of Korean Atomic Bomb Survivors in Residence at Daegu and Kyungbuk, Republic of Korea.
Hyung Joon JHUN ; Byoung Gwon KIM ; Jong Tae PARK ; Su Young KIM ; Bon Min KOO ; Jin Kook KIM
Journal of Korean Medical Science 2008;23(6):1090-1093
In 1945, many Koreans, in addition to Japanese, were killed or injured by the atomic bombs dropped on Hiroshima and Nagasaki, Japan. This study compared the biological profiles of Korean atomic bomb survivors in residence at Daegu and Kyungbuk, Republic of Korea with those of a representative sample of Koreans obtained during a similar period. We evaluated anthropometric measurements, blood pressure, blood cell counts, blood chemistry, and urinalysis of survivors (n=414) and age- and sex-matched controls (n=414) recruited from the third Korea National Health and Nutrition Examination Survey conducted in 2005. Univariate analyses revealed significantly higher systolic blood pressure, white blood cell count, and serum total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and aspartate aminotransferase levels (p<0.01) in the survivors. Conversely, hemoglobin concentration, hematocrit, red blood cell count, and the proportion of positive urine occult blood (p<0.01) were lower in the survivors. Our findings suggest that biological profiles of Korean atomic bomb survivors were adversely affected by radiation exposure.
Abnormalities, Radiation-Induced
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Aged
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Biological Markers/analysis
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Female
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Humans
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Japan
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Korea
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Male
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*Nuclear Warfare
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Radiation Injuries/diagnosis/*metabolism
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Radioactive Fallout
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Survivors
8.Changes in biochemical bone markers during pregnancy and puerperium.
Byung Koo YOON ; Jeong Won LEE ; Doo Seok CHOI ; Cheong Rae ROH ; Je Ho LEE
Journal of Korean Medical Science 2000;15(2):189-193
To elucidate the changes in bone turnover during pregnancy and puerperium, we measured serially the levels of serum osteocalcin and urine deoxypyridinoline (Dpy) as markers of bone formation and bone resorption, respectively, in 22 healthy women with normal pregnancy. Nineteen non-pregnant women served as control. The Dpy levels increased significantly at 16 weeks of pregnancy and remained elevated thereafter. The levels of osteocalcin, however, were significantly decreased at 16 weeks of pregnancy and elevated later at 6 weeks postpartum. Bone turnover ratio (Dpy/osteocalcin) continued to rise during pregnancy, but returned to control levels 6 weeks after delivery. Dpy levels and bone turnover ratio during puerperium tended to be higher in 17 breast-feeding women than those of 5 exclusive bottle-feeders. In conclusion, bone resorption begins to increase from the second trimester of pregnancy and calcium release from bone tissue might play a major role in calcium homeostasis during the whole period of pregnancy as well as during lactation.
Adult
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Amino Acids/urine
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Analysis of Variance
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Biological Markers*
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Bone Resorption/physiopathology*
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Calcium/metabolism
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Female
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Human
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Lactation/physiology
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Osteocalcin/blood
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Osteoporosis/physiopathology*
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Pregnancy
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Pregnancy Complications/physiopathology*
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Puerperium/physiology*
9.Prognostic significance of E-cadherin/catenin complex expression in gastric cancer.
Young Eun JOO ; Chang Soo PARK ; Hyun Soo KIM ; Sung Kyu CHOI ; Jong Sun REW ; Sei Jong KIM
Journal of Korean Medical Science 2000;15(6):655-666
Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.
Adult
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Aged
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Cadherins/biosynthesis*
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Cytoskeletal Proteins/biosynthesis*
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Female
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Human
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Male
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Middle Age
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Prognosis
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Stomach Neoplasms/pathology
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Stomach Neoplasms/metabolism*
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Survival Analysis
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Tumor Markers, Biological/biosynthesis*
10.Pure Choriocarcinoma of Testis with Tumor-Infiltrating Lymphocytes and Granulomas.
Yonsei Medical Journal 2006;47(6):887-891
Pure choriocarcinoma is very rare in the testes, and host immune responses including tumor infiltrating lymphocytes are unusual in choriocarcinoma. This study reports a case of pure testicular choriocarcinoma with extensive lymphocytic infiltrate and granulomatous inflammation. Scrotal ultrasonography revealed a heterogeneous, hyperechoic intratesticular mass. -human chorionic gonadotropin levels were elevated in a radioimmunoassay. The hemorrhagic and necrotic solid mass was composed of two cell populations - mononuclear pleomorphic cells and intimately admixed multinucleated smudged cells. The tumor cells were positive for cytokeratin 7, epidermal growth factor receptors, human placental lactogen and p57. Many inflammatory cells were present within the tumor. The majority of infiltrating cells were CD8-positive cytotoxic cells, which also expressed granzyme-B and TIA-1. The tumor cells were positive for FasL, but negative for Fas. Therefore, this case seemed to escape the host defense response to the tumor due to the loss of Fas, although the cellular host immune response was still active.
Tumor Markers, Biological/analysis
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Testicular Neoplasms/*pathology/ultrasonography
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Male
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Lymphocytes, Tumor-Infiltrating/*pathology
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Humans
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Granuloma/*pathology/ultrasonography
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Chorionic Gonadotropin, beta Subunit, Human/metabolism
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Choriocarcinoma/*pathology/ultrasonography
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Adult