Blood group type antigens in pancreatic intraductal papillary mucinous neoplasms

BACKGROUND: There are few data on blood group(BG) types and types of pancreatic cancers. The aims of this study were to study BG types and BG-antigens in pancreatic intraductal papillary mucinous neoplasms(IPMNs). METHODS: BG type and tumor BG-antigen(glycoprotein) expression(studied by immunohistochemistry on tissue microarrays) were analyzed with regard to characteristics of 101 surgically resected pancreatic IPMNs. RESULTS: Non-O BG type predicted invasive carcinoma independently from high serum CA19-9 and male gender. BG type A was observed more frequently in women than in men. Chronic pancreatitis was more frequently seen in patients with BG type B or AB. Aberrant tumor expression(with regard to BG type) of loss of A antigen expression type occurred in 15.0% of IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm BG-antigen expression was not related to dysplasia grade or invasion. CONCLUSION: The results of the study suggest that in pancreatic IPMN, non-O BG type predicted invasive carcinoma, whereas for intratumor BG-antigen expression no specific patterns were detected with regard to the progression of glandular epithelial dysplasia or invasion.

Association of Haplotypes in Exon 4 of KLK2 Gene with Raised Serum Prostate-Specific Antigen

The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X2 = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

In vitro and in vivo analyses of a genetically-restricted antigen specific factor from mixed cell cultures of macrophage, T and B lymphocytes

An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

Serum IgG response to differentiated antigens of Helicobacter pylori

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Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma

ＩｍｍｕｎｏｈｉｓｔｏｃｈｅｍｉｃａｌｄｅｔｅｃｔｉｏｎｏｆｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎｉｎｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａＷＡＮＧＤｏｎｇ１，ＳＨＩＪｉｎｇＱｕａｎ２ａｎｄＬＩＵＦｅｎｇＸｕａｎ３Ｓｕ...

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .

Clinical significance of Fas antigen expression in gastric carcinoma

ＩＮＴＲＯＤＵＣＴＩＯＮＩｎｏｒｄｅｒｔｏｄｅｔｅｒｍｉｎｅｗｈｅｔｈｅｒＦａｓａｎｔｉｇｅｎｐｌａｙｓａｒｏｌｅｉｎｔｈｅｇａｓｔｒｉｃｃａｒｃｉｎｏｇｅｎｉｃｓｅｑｕｅｎｃｅ，ａｎｉｍｍｕｎｏｈｉｓｔｏｃｈｅｍｉｃａｌｓｔｕｄｙｏｆＦａｓａｎｔ...

Relationship between DNA ploidy, expression of ki-67 antigen and gastric cancer metastasis

ＮＴＲＯＤＵＣＴＩＯＮＫｉ６７ｉｓａｍｏｕｓｅｍｏｎｏｃｌｏｎａｌａｎｔｉｂｏｄｙｗｈｉｃｈｒｅｃｏｇｎｉｚｅｓａｎｕｃｌｅａｒａｎｔｉｇｅｎｅｘｐｒｅｓｅｄｉｎａｌｐｈａｓｅｓｏｆｔｈｅｃｅｌｃｙｃｌｅｅｘｃｅｐｔＧｏａｎｄｅａｒｌｙＧ１［１］...

Radioiodine therapy for castration-resistant prostate cancer following prostate-specific membrane antigen promoter-mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Clinical significance of changes of perioperative T cell and expression of its activated antigen in colorectal cancer patients

ＩＮＴＲＯＤＵＣＴＩＯＮＩｍｍｕｎｅｆｕｎｃｔｉｏｎｓｔａｔｕｓｉｓｃｏｒｒｅｓｐｏｎｄｅｄｔｏｇｅｎｅｓｉｓａｎｄｐｒｏｇｒｅｓｏｆｔｕｍｏｒ，ａｎｄｃｅｌｉｍｍｕｎｅｐｌａｙｓａｍａｊｏｒｒｏｌｅｉｎａｎｔｉｔｕｍｏｒｉｍｍｕｎｉｔｙ．Ｉｎｒｅ...

Activation of killer cells with soluble gastric cancer antigen combined with anti-CD3 McAb

ＩＮＴＲＯＤＵＣＴＩＯＮＴｈｅｒｅｈａｖｅｂｅｅｎｍａｎｙｒｅｐｏｒｔｓｏｎｃａｎｃｅｒｔｈｅｒａｐｙｗｉｔｈｌｙｍｐｈｏｋｉｎｅａｃｔｉｖａｔｅｄｋｉｌｅｒ（ＬＡＫ）ｃｅｌｓａｎｄｉｎｔｅｒｌｅｕｋｉｎ２（ＩＬ２），ｂｕｔｔｈｅｐｒｏｌｉｆｅ...

Expression of proliferating cell nuclear antigen in polyps from large intestine

Ｃｏｌｏｎｃａｎｃｅｒｈａｓａｈｉｇｈｉｎｃｉｄｅｎｃｅｉｎｔｈｅｗｏｒｌｄ，ｅｓｐｅｃｉａｌｙｉｎＷｅｓｔｅｒｎｃｏｕｎｔｒｉｅｓ，ａｎｄｔｈｅｉｎｃｉｄｅｎｃｅｉｓａｌｓｏｉｎｃｒｅａｓｉｎｇｉｎＣｈｉｎａｉｎｒｅｃｅｎｔｙｅａｒｓ．Ｔｏｒｅｄｕ...

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Influence of norcantharidin on proliferation,proliferation-related gene proteins prolifera-ting cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC-SD cells

BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be consi- dered for palliative treatment such as chemotherapy and ra- diotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carci- noma were cultured by the cell culture technique. The ex- periment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of prolifera- tion-related gene proteins PCNA and Ki-67 of human gall- bladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose- and time-dependent manner, with the IC50 value of 56.18 μg/ ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932 ±0.031 vs. 0.318 ±0.023, P<0.001) and Ki-67 (0.964 ±0.092 vs. 0.297 ±0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expres- sion of their proliferation-related gene proteins PCNA and Ki-67.

Carbohydrate antigen 19-9 — tumor marker: Past, present, andfuture

Carbohydrate antigen 19-9 (CA 19-9) is a cell surface glycoprotein complex mostcommonly associated with pancreatic ductal adenocarcinoma (PDAC). Koprowskifirst described it in 1979 using a mouse monoclonal antibody in a colorectalcarcinoma cell line. Historically, it is one of the most commonly used tumormarkers for diagnosing, managing, and prognosticating PDAC. Additionally,elevated CA 19-9 levels are used as an indication for surgery in suspected benignpancreatic conditions. Another common application of CA 19-9 in the biliary tractincludes its use as an adjunct in diagnosing cholangiocarcinoma. However, itsclinical value is not limited to the hepatopancreatobiliary system. The reality isthat the advancing literature has broadened the clinical value of CA 19-9. Thepotential value of CA 19-9 in patients' workup extends its reach to gastrointestinalcancers – such as colorectal and oesophageal cancer – and further beyond thegastrointestinal tract - including urological, gynecological, pulmonary, andthyroid pathologies. Apart from its role in investigations, CA 19-9 presents apotential therapeutic target in PDAC and acute pancreatitis. In a bid toconsolidate its broad utility, we appraised and reviewed the biomarker’s currentutility and limitations in investigations and management, while discussing thepotential applications for CA 19-9 in the works for the future.

Prognostic factors in resectable cholangiocarcinoma patients: Carcinoembryonic antigen, lymph node, surgical margin and chemotherapy

AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation,tumor data, and receiving adjuvant chemotherapy were determined by uniand multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.

Detection of human liver-specific F antigen in serum and its preliminary application

ＩＮＴＲＯＤＵＣＴＩＯＮＡｓｐａｒｔａｔｅａｍｉｎｏｔｒａｎｓｆｅｒａｓｅ（ＡＳＴ）ａｎｄａｌａｎｉｎｅａｍｉｎｏｔｒａｎｓｆｅｒａｓｅ（ＡＬＴ）ａｃｔｉｖｉｔｙａｒｅｕｓｕａｌｙｕｓｅｄａｓｂｉｏｃｈｅｍｉｃａｌｃｒｉｔｅｒｉａｆｏｒｔｈｅｅｖａｌ...

Effect of cytotoxic T-lymphocyte antigen-4,TNF-alpha polymorphisms on osteosarcoma: evidences from a meta-analysis

Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.

PROLIFERATING CELL NUCLEAR ANTIGEN(PCNA) IN OVARIAN CARCINOMA AND ITS RELATION TO LYMPH NODE METASTASIS AND PROGNOSIS

Objective: To investigate expression of proliferating cell nuclear antigen (PCNA) in ovarian epithelial cancer and its relation to lymph node metastasis, outcome of second look laparotomy (SLL) and prognosis Methods: Monoclonal antibody PC10 was used to stain PCNA in archival paraffin embedded tissues Results: PC10 immunostaining was performed successfully in all 74 primary and 31 intraperitoneal metastatic tumors The expression levels of PCNA were significantly increased in 31 metastatic tumors compared with their primary tumor from the same patients (7 94 vs 6 89, P=0 042) The expression levels was more elevated in bilateral than in unilateral ovarian cancer, but it was not associated with lymph node metastasis, clinical stage, histological grade and subtype In 28 patients with stage III ovarian cancer undergone SLL, the mean immunoreactive score (IRS) of PCNA of the primary tumor was significantly higher in patients with negative SLL than in those with positive SLL (7 59 vs 6 10, P =0 03) Since chemotherapy was performed following surgical debulking, negative SLL more frequently seen in patients with high PCNA expression might suggest better chemotherapeutic sensitivity due to higher proliferation fraction of tumor cell Univariate analysis of survival indicated that the overall survival was inversely associated with the level of PCNA expression, while multivariate analysis with Cox's model showed that independent prognostic factors were the residual tumor after primary debulking ( P<0 001 ) and clinical stage ( P <0 05), followed by PCNA expression( P =0 09) Conclusion: The expression of PCNA may beuseful in predicting the patients' prognosis, but is not correlated with lymph node metastasis