BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score > or = 2. From 2006 to 2011, among the 150 DLBCL patients aged < or = 60 years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients. RESULTS: DLBCL patients with an aaIPI score > or = 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.
Adolescent ; Adult ; Age Factors ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/blood ; Chemotherapy, Adjuvant ; Cyclophosphamide/therapeutic use ; Disease Progression ; Disease-Free Survival ; Doxorubicin/therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; L-Lactate Dehydrogenase/blood ; Lymphoma, Large B-Cell, Diffuse/blood/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Predictive Value of Tests ; Prednisone/therapeutic use ; Proportional Hazards Models ; Reproducibility of Results ; Risk Assessment ; Risk Factors ; *Stem Cell Transplantation ; Time Factors ; Transplantation, Autologous ; Treatment Outcome ; Up-Regulation ; Vincristine/therapeutic use ; Young Adult

Anti-f(ce) has been associated with hemolytic transfusion reaction (HTR) and hemolytic disease of the fetus and newborn (HDFN), however, anti-Cs(a) has not been associated with red blood cell (RBC) destruction. Although anti-Cs(a) has clinical insignificance as a high-titer low-avidity (HTLA) antibody, this antibody can cause confusion in interpreting an antibody identification test, particularly coexistence of a clinically significant antibody. A 65-year-old woman with liver metastases of Klatskin tumors and cholangitis was admitted to the hospital for abdominal pain. She developed hematochezia on hospital day 10. She was at the status of active bleeding and required transfusion. The result of antibody identification test was warm-reactive autoantibody and unidentifiable alloantibody, therefore, the least incompatible packed RBCs had to be transfused to the patient. No hemolytic transfusion reaction occurred and hemoglobin level was normalized. Thereafter, anti-f(ce) and anti-Cs(a) antibodies were identified in the patient's serum. To the best of our knowledge, this is the first report of anti-f and anti-Cs(a) antibodies in Korea.
Abdominal Pain ; Aged ; Antibodies* ; Blood Group Incompatibility ; Cholangitis ; Erythrocytes ; Female ; Fetus ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Infant, Newborn ; Klatskin's Tumor ; Korea ; Liver ; Neoplasm Metastasis

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.
Actins/immunology/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Antibodies/immunology ; Carcinoembryonic Antigen/blood ; Colorectal Neoplasms/*diagnosis/mortality/pathology ; Disease-Free Survival ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/immunology/*metabolism ; Middle Aged ; Neoplasm Staging ; Phenotype ; Prognosis ; S100 Proteins/immunology/*metabolism ; Tumor Markers, Biological/metabolism

OBJECTIVE: To investigate the relationship between tumor-associated carbohydrate antigen sTn and endometrial carcinoma, and to evaluate the diagnostic value of 2 test methods. METHODS: A total of 200 patients were enrolled, including 100 subjects with endometrial carcinoma, 42 healthy nonpregnant women, 15 pregnant women without complications, and 43 patients with benign gynecologic diseases. The serum sTn-antigen concentrations were determined by 2 test methods (3P9 combined with 4A6, and B72.3 combined with CC49). RESULTS: There was a significant difference in the value and the positive rate of sTn in the serum between the subjects and the contrasts (P<0.05). The sTn level in the pregnant women was high. The sTn level in the serum and its positive rate in endometrial carcinoma became higher with the clinical stage. 3P9 combined with 4A6 was better than B72.3 combined with CC49 in the detection of sTn in the serum as to sensitivity, specificity, positive-prediction, negative-prediction, and accuracy. CONCLUSION The sTn antigen may become a new serological marker for the diagnosis of endometrial carcinoma, but pregnant women should be excluded. 3P9 combined with 4A6 is better than B72.3 combined with CC49 in the detection of sTn in the serum.
Antibodies, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; immunology ; Biomarkers, Tumor ; blood ; Case-Control Studies ; Endometrial Neoplasms ; blood ; diagnosis ; Female ; Humans

OBJECTIVETo assess the correlation between familial clustering of hepatocellular carcinoma (HCC) and the level of anti-P53 in human serum in Guangxi.

METHODSEnzyme-linked immunosorbent assay (ELISA) was used to detect anti-P53 in 164 members from 20 HCC families and 164 members from non-cancer control families. Univariate analysis was performed to assess the correlation between seral level of P53 antibody and familial clustering of HCC.

RESULTSThe level of P53 antibody was significantly higher in the members of HCC families than controls (Z=-3.04, P=0.002). After eliminating the interference of hepatitis B virus infection, this tendency still remains (P=0.011). And there was a significant difference between relatives of different degrees from HCC families (chi-square=11.593, P=0.021), with the expression of anti-P53 declining along with decrease in relationship coefficient. Furthermore, the number of individuals with high anti-P53 expression was also significantly greater in HCC families (95/164) than controls (71/164) (P=0.006). And the expression was rising along with the increasing HCC numbers (chi-square=16.068, P=0.000). Anti-P53 level was also greater in HCC families featuring sibling affection than parental affection (chi-square=12.679, P=0.002). Univariate analysis indicated that high expression of anti-P53 is a risk factor for development of HCC (OR=2.087, 95%CI: 1.270-3.431).

CONCLUSIONHigh level of anti-P53 expression may be a factor for the clustering of HCC families in Guangxi, China.

Adolescent ; Adult ; Antibodies, Neoplasm ; blood ; genetics ; Carcinoma, Hepatocellular ; blood ; genetics ; immunology ; Child ; China ; Cluster Analysis ; Family Health ; Female ; Humans ; Liver Neoplasms ; blood ; genetics ; immunology ; Male ; Risk Factors ; Tumor Suppressor Protein p53 ; immunology ; Young Adult

INTRODUCTIONLymphangiogenesis has been reported to be important in the prognosis of several tumours. The aim of this study was to assess the correlation between lymphangiogenesis and clinicopathological prognostic parameters in patients with clear cell renal cell carcinoma.

METHODS62 patients with renal cell carcinoma were included in the study. The D2-40 antibody, assessed immunohistochemically for each patient, was used as a marker. Light microscopy was used to determine the presence of intratumoral lymphatic vessels (ILVs) and the number of peritumoral lymph vessels (PLVs)/mm2 or PLV density (PLVD). Correlation between the numbers and the Fuhrman nuclear grade, tumour stage, distant metastasis status, presence of lymph node metastasis and lymphovascular invasion was assessed.

RESULTSA significant correlation was found between the presence of ILVs and distant metastasis (p = 0.033) and lymph node metastasis (p = 0.024). However, no significant correlation was found between the Fuhrman nuclear grade (p = 0.553), tumour stage (p = 0.464) and lymphovascular invasion (p = 0.242). Mean PLVD was 20.8, and no significant difference was found between the patients with PLVD below average and those with PLVD above average in terms of distant metastasis (p = 0.337), lymph node metastasis (p = 0.792), the Fuhrman nuclear grade (p = 0.566), tumour stage (p = 0.795) and lymphovascular invasion (p = 0.942).

CONCLUSIONWe found a significant correlation between ILVs and lymph node and distant metastases in patients with renal cell carcinoma.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; blood supply ; metabolism ; secondary ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; blood supply ; metabolism ; pathology ; Lymph Nodes ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the inhibitory effects of humanized monoclonal antibody-3 (huTNT-3) mediated truncated tissue factor (tTF) on the H(22) hepatoma-bearing mice, and to explore its mechanisms.

METHODSThe coagulation activity of the huTNT-3/tTF fusion protein was detected by clotting assay and clotting factor X (FX) activation test in vitro. Mouse hepatoma cell line H(22) cells were inoculated subcutaneously into mice to establish the mouse models of hepatoma. The mice were randomly divided into two groups to be injected once with huTNT-3/tTF fusion protein or tTF protein labeled with rhodamine B isothiocyanate (RBITC), respectively. The localization of huTNT-3/tTF fusion protein in the mouse hepatoma tissue was analyzed by confocal laser scanning microscopy 24 hour after the injection. Fifteen mice were randomly divided into three groups to be injected with the huTNT-3/tTF fusion protein, tTF protein or phosphate buffered saline (PBS) once, respectively. The tumor size was measured every two days to calculate the tumor volume. Ten days after the injection the mice were sacrificed. Samples of the tumor, heart, livers, spleen, lung, kidney and brains of the mice were taken for histopathological examination.

RESULTSBoth the huTNT-3/tTF fusion protein and tTF protein effectively promoted blood coagulation. Under the conditions of Ca(2+), the coagulation time in the 1.5, 3, 6 µmol/L huTNT-3/tTF groups was (12.90 ± 0.60) min, (10.39 ± 0.40) min and(8.15 ± 0.24) min, respectively, and the coagulation time of the 1.5, 3, 6 µmol/L tTF groups was (14.23 ± 0.46) min, (12.10 ± 0.49) min and (9.83 ± 0.52) min, respectively, the difference between the two groups was not significant (F = 0.145, P = 0.705). The huTNT-3/tTF fusion protein was similar to the tTF protein in the ability of activating FX (t = 0.101, P > 0.05). The confocal laser scanning microscopic analysis showed that RBITC-fluorescence labeled huTNT-3/tTF fusion protein was enriched in the hepatoma tissue. The tumor volume of the huTNT-3/tTF fusion protein group was significantly lower than that of the tTF and PBS groups (both P < 0.001), however, there was not significant difference between the tTF and PBS groups (t = -0.616, P > 0.05). The survival time of the huTNT-3/tTF group was (25.5 ± 2.5) d, significantly longer than that of the PBS group (17.3 ± 1.9) d and the tTF group (18.6 ± 1.9) d, (both P < 0.05).

CONCLUSIONThe huTNT-3/tTF fusion protein retains the coagulation ability and has the capability of targeting to tumor vasculature, and induces thrombosis in the tumor vessels, thus to suppress the growth of hepatoma in the mice.

Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Blood Coagulation ; Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Cell Line, Tumor ; Factor X ; metabolism ; Liver Neoplasms ; blood ; pathology ; therapy ; Male ; Mice ; Neoplasm Transplantation ; Random Allocation ; Recombinant Fusion Proteins ; therapeutic use ; Thromboplastin ; therapeutic use ; Tumor Burden

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.
Adult ; Aged ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Carcinoma, Squamous Cell ; blood ; diagnosis ; pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Early Detection of Cancer ; methods ; Female ; Herpesvirus 4, Human ; immunology ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Survival Rate

PURPOSE: Distant metastasis and recurrence are major prognostic factors associated with breast cancer. Both lymphovascular invasion (LVI) and blood vessel invasion (BVI) are important routes for metastasis to regional lymph nodes and for systemic metastasis. Despite the importance of vascular invasion as a prognostic factor, application of vascular invasion as a histopathological criterion is controversial. The aim of this study was to distinguish LVI from BVI in prognosis and recurrence of breast cancer using an endothelial subtype specific immunohistochemical stain (podoplanin, D2-40, and CD31). METHODS: Sections from 80 paraffin-embedded archival specimens of invasive breast cancer were stained for podoplanin, D2-40, or CD31 expression. Immunohistochemical staining results were correlated with clinicopathological features, such as tumor size, status of lymph node metastases, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor-2 expression, and recurrence. Patients with ductal carcinoma in situ and stage IV breast cancer were excluded. RESULTS: A significant correlation was found between D2-40 LVI positivity and lymph node metastasis (p=0.022). We found a significant correlation between D2-40 LVI positivity and recurrence of breast cancer (p=0.014). However, no significant correlation was found between BVI and recurrence. A poorer disease free survival was shown for D2-40 positive LVI (p=0.003). In a multivariate analysis, the presence of D2-40 LVI positivity revealed a significant association with decreased disease-free survival. CONCLUSION: D2-40 LVI positivity was a more prognostic predictor of breast cancer than BVI.
Antibodies, Monoclonal, Murine-Derived ; Antigens, CD31 ; Blood Vessels ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Disease-Free Survival ; Epidermal Growth Factor ; Estrogens ; Glycosaminoglycans ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptors, Progesterone ; Recurrence

BACKGROUND AND OBJECTIVEEarly diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC.

METHODSA proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later.

RESULTSEight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples.

CONCLUSIONSELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.

Adult ; Aged ; Algorithms ; Antibodies, Viral ; blood ; Antigens, Viral ; blood ; Biomarkers, Tumor ; blood ; Capsid Proteins ; blood ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; Neoplasm Proteins ; blood ; Proteomics ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods