P–055 Methylation dynamics of the sperm epigenome after chemotherapy: a case study

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A S Neyroud ◽  
A Rolland ◽  
B Evrard ◽  
N Alary ◽  
N Dejucq-Rainsford ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Methylation Status ◽  
Testicular Tumor ◽  
Testicular Germ Cell Tumor ◽  
Testicular Germ Cell ◽  
Paternal Genome ◽  
Reduced Representation ◽  
Before And After ◽  
Registration Number ◽  
Pre Treatment

Abstract Study question What is the evolution of the sperm epigenome after chemotherapy in a patient with testicular cancer (TC)? Summary answer These new data on epigenetic recovery profil after TC are useful tools for counseling and reassuring these patients. What is known already An important issue for young men affected TC is how TC and its treatment will affect, transiently or permanently, their future reproductive health. The consequences of cancer treatment on the sperm epigenome during the recovery periods are topical issues of ascendant significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. Study design, size, duration Here we report the epigenomic profiling of frozen sperm from a TC patient before and after the treatment at different time points (6, 9, 12 and 24 months) by using RRBS analysis (Reduced representation bisulfite sequencing method). Participants/materials, setting, methods A testicular tumor (testicular germ cell tumor) was diagnosed in a 30 years old patient. A cryopreservation of spermatozoa was proposed before treatment.Semen samples were obtained 2 times before treatment and 4 times after treatment (6, 9, 12 and 24 months following the initiation of treatment). Main results and the role of chance Upon collection, sampling after chemotherapy ranged from 0,6 to 4,2 million per sperm straw between 6 and 24 months after the treatment, always increasing. In order to capture the direct effect of the treatment on the methylation changes, the DMR detection has been operated between pre-chemotherapy samples (pair-wise) and the time point of 6 months. Among the 179 hqDMRs, 74 are differentially methylated between the PreCT and PostCT6m samples (16 hyper- and 68 hypo-methylated) associated with 49 DMGs (15 hyper- and 34 hypo-methylated). We further sub-clustered the 74 hqDMRs between PreCT and PostCT6m into 6 patterns, 3 hyper- and 3 hypo-methylated. Briefly, patterns P1 and P4 include hqDMRs that quickly get back to their pre-treatment methylation status just after 9th months onwards. Patterns P2 and P5 include hqDMRs that slowly get back to their pre-treatment methylation status between 12 and 24 months after treatment. Patterns P3 and P6 include hqDMRs that remain hyper- or hypo-methylated even after 24 months. We have intersected the genes (DMGs) associated with the detected hqDMRs with those known to be important or expressed during embryogenesis. We thus detected that 7 hyper-methylated and 6 hypomethylated DMGs were involved (or expressed) during embryonic / fetal development. Limitations, reasons for caution This study involves a single patient. As the patient made no major changes in his personal way of life, we hypothesized that sperm parameter variations may be attributable to the BEP treatment. Wider implications of the findings: The altered methylated status of those DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis leading to potential developmental disorders. It is important to notice that among the 110 DMGs none of them correspond to known imprinted genes. Trial registration number Not applicable

scholarly journals Frequency and morphological study of testicular germ cell tumor.

2019 ◽  
Vol 26 (10) ◽  
pp. 1794-1798
Author(s):  
Jawed Iqbal ◽  
Shahnaz Imdad Kehar ◽  
Nazish Jaffer ◽  
Farah Asad
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Testicular Tumor ◽  
Testicular Germ Cell Tumor ◽  
Clinical Information ◽  
Cell Tumor ◽  
International Studies ◽  
Testicular Germ Cell ◽  
Cross Sectional

Objectives: To assess the frequency of various histopathological types of testicular germ cell tumor in our study population. The prime identification of testicular germ cell tumor is important to prevent the advance stage of cancers. The present study was design to assess the frequency of different morphological types of testicular germ cell tumor which have a mirror effect on the treatment and prognosis of tumor. Study Design: Cross sectional study. Setting: Department of pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre Karachi. Period: 10 years period from 1st January 2006 to 31st December 2015. Material and Methods: A 34 cases of testicular germ cell tumor were studied for morphological features using all properly formalin fixed, paraffin embedded surgical pathological testicular specimens received during the above period. All relevant clinical information was recorded on designed proformas. Section were taken and stained with hematoxylin and eosin. Data entered and analysed through computer software SPSS version 21. Results: The result of study showed that the frequency of testicular germ cell tumor was 0.80% among all malignancy in male. Out of 36 cases of testicular tumor, 34 (94.5%) were germ cell tumors and remaining 02 (5.5%) cases were sex cord stromal tumor.  Among 34 cases of germ cell tumor 12 (35.2%) cases of mixed germ cell tumor found which was the most common between them, followed by seminoma 10 (29.4%) cases. However 05(14.7%) of yolk sac tumor, 04 (11.6%) of teratoma and 03(8.8%) of embryonal tumor were found. Conclusion: Results revealed that frequency of different types of testicular germ cell tumor in this study were in accordance to national and international studies. However the incidence of tumor varies noticeably in different geographical areas. Different pattern of seminomas and non – seminomas also may be emerging.

Malignant Testicular Germ Cell Tumor in Father and Son: A Case Report

1989 ◽  
Vol 75 (2) ◽  
pp. 177-180 ◽  
Author(s):  
Sergio Crispino ◽  
Giusi Lombardi ◽  
Giorgio Bratina ◽  
Paolo Lissoni ◽  
Sandro Barni ◽  
...  
Keyword(s):  
Case Report ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Embryonal Carcinoma ◽  
Malignant Tumors ◽  
Testicular Tumor ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell ◽  
Father And Son

This is the eighteenth case of testicular tumor in a father and son reported in the literature. The father had a seminoma and the son an embryonal carcinoma. The trend favoring more malignant tumors occurring at younger ages in the sons is confirmed by this report.

Abstract 40: Transcriptome and DNA Methylation Changes in Patients with Subarachnoid Hemorrhage Undergoing Remote Ischemic Preconditioning

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Elina Nikkola ◽  
Arthur Ko ◽  
Mark J Connolly ◽  
Yinn Cher Ooi ◽  
Päivi Pajukanta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Methylation Status ◽  
Gene Expression Profiles ◽  
Reduced Representation ◽  
Ischemic Conditioning ◽  
Genome Wide ◽  
Reduced Representation Bisulfite Sequencing ◽  
Before And After

Background: Remote ischemic conditioning (RIC) is a phenomenon by which brief periods of sublethal ischemia in one tissue confers protection from ischemia to distant tissues. We hypothesize that RIC triggers a cascade of integrated gene expression and methylation changes, leading to neuroprotection in subarachnoidal hemorrhage (SAH) patients. Our goal was to identify and compare changes in DNA methylation and gene expression profiles before and after RIC. Methods: Patients enrolled in a clinical trial of RIC after SAH, receiving RIC by limb cuff transient ischemia sessions. Fourteen SAH patients (64% female, mean age 51) underwent 3-4 RIC sessions and gave a blood sample before and after RIC, seven days apart. The transcriptome analysis of whole blood was performed using paired-end, 100-bp RNA-sequencing. We employed STAR and HTSeq to align and count reads; EdgeR to normalize the counts and detect differential expression (DE); and David to search for functional categories of the DE genes. Genome-wide DNA methylation profiles were assessed using reduced representation bisulfite sequencing (RRBS); Bismark with Bowtie to align the RRBS data, and the differential methylation analysis package (DMAP) to call the methylation status of CpG sites. Bedtools was used to overlap the DE genes with differentially methylated regions. Results: Of the 12,411 genes passing QC, 168 genes were differentially expressed after RIC (FDR<0.05). These genes were enriched for pathways involving mitosis and nuclear division (P50% after RIC in at least one individual. Of the 8,069 sites, 723 were differentially methylated (Bonferroni P<0.05). Our overlap analysis showed that 88 of the significantly altered methylation sites resided in 39 DE genes, including CEACAM8 and CRISP3, both implicated previously for stroke. Conclusions: Our data suggest that RIC alters expression of a specific set of genes involved in stroke via changes in regional DNA methylation. Further studies are warranted to replicate these pilot results.

scholarly journals Cryptorchidism: its influence on male fertility and the risk of the testicular tumor

2018 ◽  
Vol 5 (10) ◽  
pp. 3453
Author(s):  
Sujan Narayan Agrawal
Keyword(s):  
Undescended Testis ◽  
Testicular Tumor ◽  
Testicular Germ Cell Tumor ◽  
Abdominal Pressure ◽  
Differential Growth ◽  
Testicular Germ Cell ◽  
Ectopic Testis ◽  
Congenital Hernia ◽  
Bilateral Cryptorchidism ◽  
Calcitonin Gene

In the embryonic stage, the testes develop in the abdomen and descend to scrotum, just before or at birth. The undescended testis is the result of the arrest of descent of testis in some part along its path, to the scrotum. The bilateral undescended testis is called Cryptorchidism which means hidden testis. The factors that contribute to the descent of testis includes Gubernaculum testis, the differential growth of abdominal wall, intra-abdominal pressure and temperature, Calcitonin gene-related peptide (CGRP), male sex hormones, insulin-like hormone 3 (INSL3) and maternal gonadotrophins. The descent of testis may become erratic and gives rise to undescended testis, ectopic testis, congenital hernia, and hydrocoele etc. As a rough estimate approximately 2-4% of male infants are born with Cryptorchism, thus making it, one of the most common congenital anomalies, in the male genitalia. It was found that the incidence of azoospermia in unilateral cryptorchidism was 13%, but in untreated bilateral cryptorchidism, it reaches up to 89%. Cryptorchid boys have increased the risk of a testicular tumor, mainly seminoma. Persistent exposure to high temperature in cryptorchidism could allow maturation of the neonatal gonocytes that has failed to mature as spermatogonia or undergo apoptosis. These cells may persist in testes for years together and eventually become carcinoma in situ cells with a high risk of testicular malignancy later in life i.e., 20-40 years of age. This review addresses the cryptorchidism, its influence on fertility and the risk of developing testicular germ cell tumor. The hormonal factors involved in testicular descend or otherwise is also highlighted.

scholarly journals Collision tumor comprising metastatic cholangiocarcinoma and seminoma in an undescended testis: a case report

2019 ◽  
Vol 47 (11) ◽  
pp. 5809-5816
Author(s):  
Chang Gok Woo ◽  
Ok-Jun Lee ◽  
Yaewon Yang ◽  
Yong June Kim ◽  
Jisun Lee ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Undescended Testis ◽  
Testicular Tumor ◽  
Testicular Germ Cell Tumor ◽  
Fold Increase ◽  
Collision Tumor ◽  
Common Type ◽  
Testicular Germ Cell ◽  
Testicular Metastasis ◽  
First Case

Testicular metastasis of solid tumors is uncommon. Common primary sites of metastatic tumors to the testis are the lungs and prostate. Cryptorchidism is associated with a four-fold increase in the risk of a testicular germ cell tumor of which seminoma is the most common type. We report an extremely rare case of a collision tumor that comprised testicular metastasis of intrahepatic cholangiocarcinoma and a seminoma in an undescended testis. To the best of our knowledge, this is the first case of this type of tumor to be described. Awareness that metastatic intrahepatic cholangiocarcinoma may present as a testicular tumor may aid diagnosis and management of such patients.

METASTATIC CARDIAC TUMORS: LITERATURE REVIEW AND OWN OBSERVATION OF TESTICULAR TUMOR METASTASIS IN THE RIGHT VENTRICLE OF THE HEART

2018 ◽  
Vol 40 (4) ◽  
pp. 336-342 ◽  
Author(s):  
L M Zakhartseva ◽  
L P Zakharova ◽  
K M Shatrova ◽  
G E Chitaeva ◽  
R M Vitovsky
Keyword(s):  
Literature Review ◽  
Right Ventricle ◽  
Histological Study ◽  
Testicular Tumor ◽  
Malignant Neoplasm ◽  
Testicular Germ Cell Tumor ◽  
Diagnostic Algorithm ◽  
Cardiac Tumors ◽  
Testicular Germ Cell ◽  
The Right

Background: Tumors of the heart are uncommon and usually benign (in 93% cases myxomas are observed). More often secondary, metastatic tumors are detected in the heart, as a rule, at pronounced progression of the malignant neoplasm with multiple lesions of other internal organs (lung, pleura, liver, etc.). Literature review on cardiac metastases of different tumors is given. Case Report: Own observation of a young man with rare single metastasis of malignant testicular germ cell tumor with predominance of embryonic carcinoma in the right ventricle of the heart is presented; the primary tumor was detected after metastasis revealing. The diagnostic algorithm using routine histological study supplemented with immunohistochemistry, including detection of cytokeratin pan, cytokeratin 5/6, cytokeratin 7, CD30, OCT4, TTF-1, hCG, and AFP markers expression, is described.

Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cell Viability ◽  
Neuronal Cells ◽  
Positive Control ◽  
Post Treatment ◽  
Mitochondrial Activity ◽  
Before And After ◽  
Pre Treatment ◽  
Tocotrienol Rich Fraction ◽  
Major Mediator

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

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.

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