scholarly journals Clinical Significance of Amyloid Precursor Protein in Patients with Testicular Germ Cell Tumor

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yuta Yamada ◽  
Tetsuya Fujimura ◽  
Satoru Takahashi ◽  
Kenichi Takayama ◽  
Tomohiko Urano ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Germ Cell ◽  
Mrna Expression ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Venous Invasion ◽  
Precursor Protein ◽  
Testicular Germ Cell ◽  
Aggressive Cancer

Introduction. The biological role of amyloid precursor protein (APP) is not well understood, especially in testicular germ cell tumors (TGCTs). Therefore, we aimed to investigate the immunoreactivity (IR) and expression of APP in TGCTs and evaluated its clinical relevance.Materials and Methods. We performed an analysis of immunohistochemistry and mRNA expression of APP in 64 testicular specimens and 21 snap-frozen samples obtained from 1985 to 2004. We then evaluated the association between APP expression and clinicopathological status in TGCTs.Results. Positive APP IR was observed in 9.8% (4/41) of seminomatous germ cell tumors (SGCTs) and 39.1% (9/23) of nonseminomatous germ cell tumors (NGCTs). NGCTs showed significantly more cases of positive IR(P=0.00870)and a higher mRNA expression level compared with those of SGCTs(P=0.0140). Positive APP IR was also significantly associated withα-fetoprotein (αFP) elevation(P=0.00870)and venous invasion(P=0.0414).Conclusion. We observed an elevated APP expression in TGCTs, especially in NGCTs. APP may be associated with a more aggressive cancer in TGCTs.

Clinical significance of amyloid precursor protein in patients with testicular germ cell tumor.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Germ Cell ◽  
Clinical Significance ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Precursor Protein ◽  
Testicular Germ Cell ◽  
Nonseminomatous Germ Cell Tumor ◽  
Yolk Sac Tumors

Testicular cancer is a relatively rare cancer that accountsfor approximately 1–1.5% of male cancers, and 90–95%of these cancers are testicular germ cell tumors (TGCTs)[1]. TGCTs can be classified into two major histologicalcategories, namely, seminomatous germ cell tumor (SGCT)and nonseminomatous germ cell tumor (NGCT). NGCTs,which include yolk sac tumors, embryonal cell carcinomas,teratomas, and choriocarcinomas, are different from SGCTswith regard to clinical characteristics and therapy required.Amyloid precursor protein (APP) is a type 1transmembrane protein that is considered to play a key rolein Alzheimer’s disease. It has multiple isoforms attributableto alternative splicing and is expressed in various types ofhuman cells. APP695 predominantly exists in the neuronswhereas other isoforms such as the APP751 and APP770are expressed in nonneuronal cells [2]. The biological roleof APP is not well understood. APP and its cleaved formshave been suggested to mediate various functions, includingcell adhesion [3], cell signaling [4], and cell growth [5–7].These functions are important in carcinogenesis, and APPexpression may be involved in the development of variouscancers [8–13].We have previously shown that APP is a primaryandrogen-responsive gene that promotes the growth of2 Advances in Urologyprostate cancer cells [14]. In the present study, we investigatedAPP immunoreactivity (IR) and APP mRNA expression inTGCTs and evaluated its clinical significance.

Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors

2018 ◽  
Vol 25 (5) ◽  
pp. 575-583 ◽  
Author(s):  
Paolo Chieffi
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cells ◽  
Germ Cell Tumors ◽  
Molecular Targets ◽  
Testicular Germ Cell Tumor ◽  
Research Literature ◽  
Testicular Germ Cell ◽  
Solid Malignancy ◽  
Bibliographic Data ◽  
New Biomarkers

Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Methods: I undertook a search of bibliographic data from peer-reviewed research literature. Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies. Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.

scholarly journals Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study

2021 ◽  
Vol 27 ◽  
pp. 107602962110247
Author(s):  
Hikmat Abdel-Razeq ◽  
Faris Tamimi ◽  
Rashid Abdel-Razeq ◽  
Samer Salah ◽  
Zaid Omari ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Germ Cell ◽  
Metastatic Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Tumor Burden ◽  
Testicular Tumors ◽  
Testicular Germ Cell ◽  
Node Positive ◽  
Age Range

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

scholarly journals Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
João Lobo ◽  
Vera Constâncio ◽  
Pedro Leite-Silva ◽  
Rita Guimarães ◽  
Mariana Cantante ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Complete Response ◽  
Differential Analysis ◽  
Testicular Germ Cell ◽  
Tissue Samples ◽  
Tumor Patient ◽  
Resistant Disease ◽  
Response To Chemotherapy

AbstractTesticular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.

Testicular Germ Cell Tumor and down Syndrome

2000 ◽  
Vol 86 (5) ◽  
pp. 431-433 ◽  
Author(s):  
María José Villanueva ◽  
Fátima Navarro ◽  
Antonio Sánchez ◽  
Mariano Provencio ◽  
Félix Bonilla ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Medical Literature ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
English Medical Literature

The association between Down syndrome and testicular germ cell tumors may be more frequent than expected according to chance, but few reports have focused on this excess. We report two cases of this association and review the English medical literature.

Evidence for Altered Hypothalamic-Hypophyseal-Gonadal Axis in Untreated Patients with Testicular Germ-Cell Tumor

1989 ◽  
Vol 75 (5) ◽  
pp. 505-509
Author(s):  
Sergio Crispino ◽  
Gabriele Tancini ◽  
Sandro Barni ◽  
Paolo Lissoni
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Venous Blood ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Significant Difference

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 μg as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, nonseminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the Physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.

scholarly journals The Role of the Mouse Y Chromosome on Susceptibility to Testicular Germ Cell Tumors

2009 ◽  
Vol 69 (8) ◽  
pp. 3614-3618 ◽  
Author(s):  
Philip D. Anderson ◽  
Man-Yee Lam ◽  
Christophe Poirier ◽  
Colin E. Bishop ◽  
Joseph H. Nadeau
Keyword(s):  
Germ Cell ◽  
Y Chromosome ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Current Insights into Interethnic Variability in Testicular Cancers: Population Pharmacogenetics, Clinical Trials, Genetic Basis of Chemotherapy- Induced Toxicities and Molecular Signal Transduction

2020 ◽  
Vol 20 (20) ◽  
pp. 1824-1838 ◽  
Author(s):  
Aman Vasistha ◽  
Rishi Kothari ◽  
Adarsh Mishra ◽  
Fernando De Andrés ◽  
Adrián LLerena ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Clinical Trials ◽  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Surgical Removal ◽  
Genetic Determinants ◽  
Testicular Germ Cell ◽  
Aggressive Cancer ◽  
Molecular Signal

Testicular cancer is an aggressive malignancy with a rising incidence rate across the globe. Testicular germ cell tumors are the most commonly diagnosed cancers, and surgical removal of the testes is often a radical necessity along with chemotherapy and radiotherapy. While seminomas are receptive to radiotherapy as well as chemotherapy, non-seminomatous germ cell tumors respond to chemotherapy only. Due to the singular nature of testicular cancers with associated orchiectomy and mortality, it is important to study the molecular basis and genetic underpinnings of this group of cancers across male populations globally. In this review, we shed light on the population pharmacogenetics of testicular cancer, pediatric and adult tumors, current clinical trials, genetic determinants of chemotherapy-induced toxicity in testicular cancer, as well as the molecular signal transduction pathways operating in this malignancy. Taken together, our discussions will help in enhancing our understanding of genetic factors in testicular carcinogenesis and chemotherapy-induced toxicity, augment our knowledge of this aggressive cancer at the cellular and molecular level, as well as improve precision medicine approaches to combat this disease.

scholarly journals Rare inactivating PDE11A variants associated with testicular germ cell tumors

2015 ◽  
Vol 22 (6) ◽  
pp. 909-917 ◽  
Author(s):  
Anand Pathak ◽  
Douglas R Stewart ◽  
Fabio R Faucz ◽  
Paraskevi Xekouki ◽  
Sara Bass ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Testicular Tissue ◽  
Transcript Variant ◽  
Coding Region ◽  
Testicular Germ Cell ◽  
Rare Mutations ◽  
Gene Study

Germline inactivating mutations of isoform 4 of phosphodiesterase (PDE) 11A (coded by the PDE11A gene) have been associated with familial adrenocortical tumors and familial testicular cancer. Testicular tissue is unique in expressing all four isoforms of PDE11A. In a prior candidate gene study of 94 familial testicular germ cell tumor (TGCT) subjects, we identified a significant association between the presence of functionally abnormal variants in PDE11A and familial TGCT risk. To validate this novel observation, we sequenced the PDE11A coding region in 259 additional TGCT patients (both familial and sporadic) and 363 controls. We identified 55 PDE11A variants: 20 missense, four splice-site, two nonsense, seven synonymous, and 22 intronic. Ten missense variants were novel; nine occurred in transcript variant 4 and one in transcript variant 3. Five rare mutations (p.F258Y, p.G291R, p.V820M, p.R545X, and p.K568R) were present only in cases and were significantly more common in cases vs controls (P=0.0037). The latter two novel variants were functionally characterized and shown to be functionally inactivating, resulting in reduced PDE activity and increased cAMP levels. In further analysis of this cohort, we focused on white participants only to minimize confounding due to population stratification. This study builds upon our prior reports implicating PDE11A variants in familial TGCT, provides the first independent validation of those findings, extends that work to sporadic testicular cancer, demonstrates that these variants are uncommonly but reproducibly associated with TGCT, and refines our understanding regarding which specific inactivating PDE11A variants are most likely to be associated with TGCT risk.

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