Antigens, Neoplasm ; analysis ; Carcinoma, Hepatocellular ; chemistry ; Humans ; Liver Neoplasms ; chemistry

Adult ; Antigens, Neoplasm ; Diagnosis, Differential ; Epithelioid Cells ; pathology ; Female ; Humans ; Immunohistochemistry ; Melanoma-Specific Antigens ; Neoplasm Proteins ; analysis ; Uterine Neoplasms ; chemistry ; diagnosis ; pathology

OBJECTIVETo determine the apoptotic and proliferative activities in various ovarian epithelial tumors.

METHODSFormalin-fixed, paraffin-embedded tissues of 86 ovarian epithelial tumors, including 52 adenocarcinomas, 23 borderline tumors and 11 cystadenoma, were retrieved. Apoptotic (AI) and proliferative (PI) index were estimated using the monoclonal antibodies: M30, Ki-67 and Ki-S1 in these tumors. Quantitative assessment of AI and PI was estimated by calculating the percentage of positive cells among no less than 1000 tumor cells.

RESULTSStatistically significant difference in AI was found between benign and borderline tumors or carcinomas (P = 0.028, 0.001, respectively). Significant differences in PI, as assessed by both Ki-67 and topo IIalpha, were demonstrated between carcinomas and benign or borderline tumors (both P < 0.001). Benign tumors had both low PI and AI; borderline tumors had lower PI but higher AI, while adenocarcinomas had both high proliferative and high apoptotic rates. Among borderline tumors, serious tumors had significantly lower AI and higher PI than mucinous ones.

CONCLUSIONThe results suggest that apoptotic and proliferative activities play important roles in the pathogenesis and development of ovarian borderline and malignant tumors. The high apoptotic rate in borderline tumor may explain its relatively indolent behavior while the high proliferative rate in carcinomas tends to explain its aggressive behavior.

Antigens, Neoplasm ; Apoptosis ; Carcinoma, Endometrioid ; chemistry ; pathology ; Cell Division ; Cystadenocarcinoma, Serous ; chemistry ; pathology ; Cystadenoma, Mucinous ; chemistry ; pathology ; Cystadenoma, Serous ; chemistry ; pathology ; DNA Topoisomerases, Type II ; analysis ; DNA-Binding Proteins ; Female ; Humans ; Ki-67 Antigen ; analysis ; Ovarian Neoplasms ; chemistry ; pathology

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.
Antigens, Neoplasm/chemistry* ; Biomarkers, Tumor/metabolism* ; Glycosylation ; Hematologic Neoplasms/drug therapy* ; Humans ; Immunotherapy, Adoptive/methods* ; Male ; Neoplasm Recurrence, Local/metabolism* ; Receptors, Chimeric Antigen ; T-Lymphocytes ; United States

Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.
Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; chemistry ; therapeutic use ; Carbonic Anhydrase IX ; Carbonic Anhydrase Inhibitors ; chemistry ; therapeutic use ; Carbonic Anhydrases ; metabolism ; Humans ; Neoplasms ; drug therapy ; enzymology

Adult ; Antigens, Neoplasm ; analysis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Melanoma ; cerebrospinal fluid ; metabolism ; pathology ; Melanoma-Specific Antigens ; Melanosis ; cerebrospinal fluid ; metabolism ; pathology ; Meningeal Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Meninges ; chemistry ; pathology ; Neoplasm Proteins ; analysis ; S100 Proteins ; analysis

Actins ; metabolism ; Adult ; Antigens, Neoplasm ; metabolism ; Diagnosis, Differential ; Epithelioid Cells ; chemistry ; pathology ; Female ; Humans ; Hysterectomy ; Immunohistochemistry ; Melanoma-Specific Antigens ; Mesenchymoma ; metabolism ; pathology ; surgery ; Neoplasm Proteins ; metabolism ; Uterine Neoplasms ; metabolism ; pathology ; surgery

One hundred large bowel carcinomas were studied immunohistochemically with regard to expression of HLA-DR antigen (DR). One or two sections from each tumor including surrounding normal mucosa were examined by a semiquantitative counting system for tumor cells and mucosal and stromal infiltrates of lymphocytes and mononuclear cells (MNCs) with DR expression and the results were applied Chi-square test. The rate of presence of DR positive (DR+) lymphocytes in lymphoid nodules and DR+ lymphocytes/ MNC in the adjacent mucosa and stroma in DR+ carcinoma (50%) was higher (P < 0.01) than in DR- carcinoma (21.9%). Thirty-six carcinomas (36%) were DR+. Three (75%) out of 4 DR+ poorly differentiated carcinomas and six (20%) out of 30 DR+ moderately differentiated carcinomas showed homogeneously strong DR+ expression. There was tendency for poorly differentiated carcinoma to be more homogeneous DR+ expression. According to Dukes' stage, four (80%) out of 5 carcinomas in Dukes' stage D were DR-. An increased infiltration of lymphocytes/MNCs into adjacent mucosa and stroma in large bowel carcinomas is possibly related with DR expression by carcinoma. From the results of this study, we postulated as follows: 1) DR+ tumor cells may act as antigen-presenting cells, 2) They may have an inhibitory effect for distant metastasis, 3) Poorly differentiated carcinoma expressed more DR+ homogeneously.
Adult ; Aged ; Antibodies ; Colorectal Neoplasms/blood/*chemistry/pathology ; Epithelium/chemistry ; Female ; HLA-DR Antigens/*analysis ; Human ; Immunohistochemistry ; Leukocytes, Mononuclear/chemistry ; Lymphocytes/chemistry ; Male ; Middle Age ; Neoplasm Staging ; Support, Non-U.S. Gov't

BACKGROUND AND OBJECTIVEAs a prospective vaccine carrier, nanoparticles can protect antigens from degradation and enhance immune response. This study prepared nanovaccines with MAGE-3-derived CD4+-CD8+T cell epitope peptides, and investigated its character and antitumor effects on transplanted gastric cancer in mice.

METHODSWe adopted the self-assembly method to prepare peptide/chitosan conjugated with deoxycholic acid (chitosan-deoxycholic acid) nanoparticles. We observed the appearance of the chitosan-deoxycholic acidnanoparticles through a transmission electron microscope (TEM) and analyzed the peptide content and its release pattern by fluorescence spectrophotometry. We observed tumor-suppression efficacy in vivo through animal experiments.

RESULTSWe successfully prepared nanoparticles with MAGE-3 peptide antigen, and its encapsulation efficiency and loading level were about 37% and 17.0%, respectively. These nanoparticles presented a delayed release pattern in phosphate buffered saline (PBS) at pH 7.4, and the full release time was about 48 h. In 2 mg/mL lysozyme, the nanoparticles showed a sudden release, and the full release time was about 24 h. ELISPOT and cytotoxic experiments showed that the MAGE-3 peptide loaded nanoparticles could stimulate immune response in vivo and could generate MAGE-3-targeted cytotoxic T lymphocytes (CTLs), and kill MAGE-3-specific tumor cells. Tumor suppression experiments showed that the regression ratio of the peptide-loaded nanoparticles group was 37.81%.

CONCLUSIONSMAGE-3 peptide/chitosan-deoxycholic acidvaccine-loaded nanoparticles can stimulate antitumor immune response in vivo and can regress the growth of mouse forestomach carcinoma cell line MFC.

Animals ; Antigens, Neoplasm ; chemistry ; immunology ; Cancer Vaccines ; administration & dosage ; Cell Line, Tumor ; Chitosan ; chemistry ; Dendritic Cells ; immunology ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Epitopes, T-Lymphocyte ; immunology ; Male ; Mice ; Nanoparticles ; Neoplasm Proteins ; chemistry ; immunology ; Neoplasm Transplantation ; Stomach Neoplasms ; pathology ; therapy ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Burden

OBJECTIVE: To search for the differentially expressed proteins of nasopharyngeal carcinoma (NPC),and provide scientific evidence for identifying molecular biomarkers for NPC. METHODS: Laser capture microdissection (LCM) was used to purify the target cells from NPC and normal nasopharyngeal epithelial tissues (NNET). Two-dimensional gel electrophoresis (2-DE) was used to separate the total proteins of microdissected NPC and NNET, PDQuest software was applied to analyze 2-DE images,and the differential proteins between the 2 types of tissues were identified by both MALDI-TOF-MS and ESI-Q-TOF-MS. Western blot and immunohistochemistry of tissue microarray were used to detect the expression of the differential protein SCCA1 in NPC and NNET. RESULTS: 2-DE patterns of microdissected NPC and NNEC were established,and 36 differential proteins in the NPC and NNEC were identified,20 of which only expressed or up-regulated in NPC and 16 only expressed or up-regulated in NNET. The differentially expressed level of SCCA1 in the NPC and NNET was confirmed by Western blot and immunohistochemistry of tissue microarray. CONCLUSION Thirty-six differentially expressed proteins identified in this study may be associated with the carcinogenesis of NPC,and may be candidate molecular biomarkers for NPC.
Amino Acid Sequence ; Antigens, Neoplasm ; isolation & purification ; Biomarkers, Tumor ; isolation & purification ; Carcinoma, Squamous Cell ; chemistry ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Lasers ; Microdissection ; methods ; Molecular Sequence Data ; Nasopharyngeal Neoplasms ; chemistry ; Neoplasm Proteins ; isolation & purification ; Proteomics ; methods ; Serpins ; isolation & purification