Antigens, Neoplasm ; metabolism ; Antigens, Surface ; metabolism ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Prognosis ; Trophoblasts ; immunology

In this study we investigate the expression pattern of mucin genes in the human testis and evaluate the relationship between the expression of mucin genes and impaired spermatogenesis in the human testis. Thirty human testis tissues were collected from patients undergoing diagnostic testicular biopsy to investigate the cause of infertility. One part of the tissue underwent histological observation, and the other part of the tissue was subjected to semiquantitative RT-PCR of mucin genes, that is, mucin1, 2, 3, 4, and 9. The relative amount of mucin mRNAs was calculated by densitometry using glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as an internal control. The samples were histologically diagnosed as either obstructive azoospermia with normal spermatogenesis (n = 13) or non-obstructive azoospermia with impaired spermatogenesis (n = 17). In the human testis with normal spermatogenesis, mRNA expression of mucin1, 9, 13 and GAPDH were found, but RT-PCR products of mucin 2, 3 and 4 were not detected. In the testis with impaired spermatogenesis, however, RT-PCR product of mucin1 was not found. There was no difference in the other mucin mRNA expression patterns between the testis with either normal or impaired spermatogenesis. To our knowledge, this study is the first that has detected the mRNA of mucin9 and 13 in human testis. This study also shows that mucin1 expression might be closely related to spermatogenesis. Our findings should be substantiated by more direct evidence, such as mucin protein expression and localization.
Testis/*metabolism ; *Spermatogenesis ; Mucins/*genetics ; Middle Aged ; Male ; Humans ; Glycoproteins/genetics ; Antigens, Neoplasm ; Antigens/genetics ; Adult

OBJECTIVETo investigate the mode of angiogenesis between highly invasive malignant melanoma and poorly invasive malignant melanoma by immunohistochemistry and periodic acid-Schiff stain (PAS) and to discuss whether the tumor cells in highly invasive malignant melanoma carry vasculogenic mimicry through self-metamorphosis, thus acquiring blood supply to sustain their growth.

METHODSThirty cases of highly invasive malignant melanoma and 30 cases of poorly invasive malignant melanoma were retrieved and reprocessed as tissue microarray for further investigations. The tissue microarray sections were then stained with CD34 and PAS; and the positivity rates were compared.

RESULTSThere was a significant difference between CD34 and PAS staining in highly invasive malignant melanoma (P < 0.01). The difference was not statistically significant in poorly invasive malignant melanoma (P > 0.05).

CONCLUSIONVasculogenic mimicry exists in some cases of highly invasive malignant melanoma. It is possible that the tumor cells can acquire blood supply to sustain growth and metastasize via this mechanism.

Antigens, CD34 ; analysis ; Antigens, Neoplasm ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Melanoma ; blood supply ; metabolism ; pathology ; Melanoma-Specific Antigens ; Neoplasm Proteins ; analysis ; Neovascularization, Pathologic ; metabolism ; pathology

BACKGROUNDThe specificity for early interventions of prostate-specific antigen (PSA) in prostate cancer (PCa) is not satisfactory. It is likely that prostate cancer antigen 3 (PCA3) can be used to predict biopsy outcomes more accurately than PSA for the early detection of PCa. We systematically reviewed literatures and subsequently performed a meta-analysis.

METHODSA bibliographic search in the database of Embase, Medline, Web of Science, NCBI, PubMed, CNKI, and those of health technology assessment agencies published before April 2013 was conducted. The key words used were "prostatic neoplasms", "prostate", "'prostate', 'carcinoma' or 'cancer' or 'tumor', or 'PCa,'" and free terms of "upm3", "pca3", "dd3", "aptimapca 3", and "prostate cancer antigen 3". All patients were adults. The intervention was detecting PCA3 in urine samples for PCa diagnosis. We checked the quality based on the QUADAS criteria, collected data, and developed a meta-analysis to synthesize results. Twenty-four studies of diagnostic tests with moderate to high quality were selected.

RESULTSThe sensitivity was between 46.9% and 82.3%; specificity was from 55% to 92%; positive predictive value had a range of 39.0%-86.0%; and the negative predictive value was 61.0%-89.7%. The meta-analysis has heterogeneity between studies. The global sensitivity value was 0.82 (95% CI 0.72-0.90); specificity was 0.962 (95% CI 0.73-0.99); positive likelihood ratio was 2.39 (95% CI 2.10-2.71); negative likelihood ratio was 0.51 (95% CI 0.46-0.86); diagnostic odds ratio was 4.89 (95% CI 3.94-6.06); and AUC in SROC curve was 0.744 1.

CONCLUSIONPCA3 can be used for early diagnosis of PCa and to avoid unnecessary biopsies.

Antigens, Neoplasm ; metabolism ; Biomarkers, Tumor ; metabolism ; Biopsy ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; metabolism

T cells play central roles in anti-tumor immune responses. Immune checkpoint therapy, which is based on modulation of T cell reactivity, has achieved breakthrough in clinical treatment of multiple tumors. Moreover, adoptive T cell therapy, which includes mainly genetically engineered T cells, has shown substantial treatment efficacy in hematoma. Immune therapy has tremendously changed the scenario of clinical tumor treatment and become critical strategies for treating multiple tumors. T cell receptor (TCR) is the fundamental molecule responsible for the specificity of T cell recognition. TCRs could recognize peptides, which are derived from intracellular or extracellular tumor antigens, presented by major histocompatibility complex (MHC) and are therefore highly sensitive to low antigen level. Thereby, TCRs are broadly recognized as promising molecules for the development of anti-tumor drugs. The approval of the first TCR drug in 2022 has initiated a new era for TCR-based therapeutics and since then, multiple TCR drugs have shown substantial treatment efficacy in multiple tumors. This review summarizes the progress of TCR-based immune therapeutic strategies, including T cell receptor-engineered T cell (TCR-T), TCR-based protein drugs, and other cell therapies based on TCR signaling, providing useful information for future design of immune therapeutics based on TCR.
Humans ; Receptors, Antigen, T-Cell/metabolism* ; T-Lymphocytes/metabolism* ; Neoplasms/metabolism* ; Immunotherapy ; Antigens, Neoplasm

T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1). These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.
Animals ; Antigens, Neoplasm ; immunology ; metabolism ; Humans ; Neoplasms ; immunology ; metabolism ; Receptors, Antigen, T-Cell ; genetics ; metabolism ; T-Lymphocytes ; immunology ; metabolism

OBJECTIVETo study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features.

METHODSThe expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject.

RESULTSImmunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue.

CONCLUSIONPSCA might play an important role in lymph node metastasis in IMPC.

Antigens, Neoplasm ; genetics ; metabolism ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Female ; GPI-Linked Proteins ; genetics ; metabolism ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Staging ; RNA, Messenger ; metabolism

Antigens, Neoplasm ; Brain ; metabolism ; pathology ; Humans ; Infant, Newborn ; Lung ; metabolism ; pathology ; Male ; Melanoma-Specific Antigens ; Melanosis ; complications ; congenital ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Neurocutaneous Syndromes ; complications ; congenital ; metabolism ; pathology ; S100 Proteins ; metabolism ; Skin ; metabolism ; pathology

BackgroundDevelopment of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy.

MethodsSixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses.

ResultsHLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/10 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders.

ConclusionMAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Antigens, Neoplasm ; immunology ; metabolism ; Carcinoma ; immunology ; metabolism ; Female ; HLA-A Antigens ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; immunology ; metabolism ; Neoplasm Proteins ; metabolism ; Sarcoma, Synovial ; immunology ; metabolism ; Young Adult

Actins ; metabolism ; Angiomyolipoma ; metabolism ; pathology ; surgery ; Antigens, Neoplasm ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Leiomyosarcoma ; metabolism ; pathology ; Mediastinal Neoplasms ; metabolism ; pathology ; surgery ; Mediastinum ; pathology ; surgery ; Melanoma-Specific Antigens ; Middle Aged ; Neoplasm Proteins ; metabolism