scholarly journals Hazard Identification: Efficiency of Short-Term Tests in Identifying Germ Cell Mutagens and Putative Nongenotoxic Carcinogens

1993 ◽  
Vol 101 ◽  
pp. 61 ◽  
Author(s):  
M. D. Waters ◽  
H. F. Stack ◽  
M. A. Jackson ◽  
B. A. Bridges
Keyword(s):  
Germ Cell ◽  
Hazard Identification ◽  
Short Term ◽  
Nongenotoxic Carcinogens

scholarly journals GCT-08. PROTON BEAM RADIOTHERAPY FOR PEDIATRIC AND YOUNG-ADULT PATIENTS WITH INTRACRANIAL GERM CELL TUMOR

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii329-iii329
Author(s):  
Minako Sugiyama ◽  
Takayuki Hashimoto ◽  
Takashi Mori ◽  
Kazuya Hara ◽  
Yukayo Terashita ◽  
...  
Keyword(s):  
Young Adult ◽  
Adverse Events ◽  
Germ Cell ◽  
Cell Count ◽  
Proton Beam ◽  
Adult Patients ◽  
Short Term ◽  
Intracranial Germ Cell Tumor ◽  
X Ray ◽  
Proton Beam Radiotherapy

Abstract BACKGROUND To reduce treatment-related adverse events in pediatric and young-adult patients with brain tumors, proton beam radiotherapy (PBT) has recently been performed instead of conventional X-ray radiotherapy. However, whether PBT is as effective as X-ray radiotherapy has not been sufficiently investigated, especially in patients receiving whole-ventricular irradiation. METHODS We report a retrospective observation of 15 patients with intracranial germ cell tumors (GCT), who received PBT at our institution from April 2014 to September 2019. We evaluated their clinical course, short-term adverse events, and prognosis. RESULTS/ CONCLUSION Fifteen patients (9 males and 6 females; median age 13 years) who received PBT following induction chemotherapy were analyzed. Nine patients received 23.4–27.0 GyE of whole-ventricular irradiation due to GCT in the pituitary gland, pineal body, or hypothalamic area. Three patients received 23.4 GyE of whole-brain irradiation: one of them had boost irradiation for basal ganglia. Three patients received 30.6 GyE of craniospinal irradiation (CSI). Six of the 15 patients experienced nausea (grade 2, according to the CTCAE version 4.0). Four patients, including two who received CSI, showed myelosuppression: decrease in white blood cell count, lymphocyte cell count, and neutrophil count (grade 3). No other severe short-term adverse events of >grade 2 was observed in any of the patients. At a median follow-up of 21 months (2-62 months) after irradiation. all patients are alive without recurrence. Our results may be encouraging and further investigations with a larger scale is warranted.

scholarly journals A Data-Based Assessment of Alternative Strategies for Identification of Potential Human Cancer Hazards

2009 ◽  
Vol 37 (6) ◽  
pp. 714-732 ◽  
Author(s):  
Alan R. Boobis ◽  
Samuel M. Cohen ◽  
Nancy G. Doerrer ◽  
Sheila M. Galloway ◽  
Patrick J. Haley ◽  
...  
Keyword(s):  
Health And Environmental Sciences ◽  
Human Cancer ◽  
Carcinogenic Risk ◽  
Hazard Identification ◽  
Testing Strategy ◽  
Short Term ◽  
Kidney Tumors ◽  
Key Events ◽  
Potential Cancer ◽  
Term Data

The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be detected in shorter-term studies. Using the National Toxicology Program (NTP) database, a retrospective analysis was conducted on sixteen chemicals with liver, lung, or kidney tumors in two-year rodent cancer bioassays, and for which short-term data were also available. For nongenotoxic compounds, results showed that cellular changes indicative of a tumorigenic endpoint can be identified for many, but not all, of the chemicals producing tumors in two-year studies after thirteen weeks utilizing conventional endpoints. Additional endpoints are needed to identify some signals not detected with routine evaluation. This effort defined critical questions that should be explored to improve the predictivity of human carcinogenic risk.

Intragonadal regulation of immune system functions

1990 ◽  
Vol 2 (3) ◽  
pp. 263 ◽  
Author(s):  
MP Hedger ◽  
JX Qin ◽  
DM Robertson ◽  
Kretser DM de
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Germ Cell ◽  
Conditioned Medium ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Interstitial Tissue ◽  
Short Term ◽  
Adult Rat

Immune responses within the mammalian gonads, and in particular the testis, are deficient in spite of adequate lymphatic drainage and the presence of lymphocytes and MHC II+ macrophages. There is considerable evidence from in vivo and in vitro studies that this 'suppression' of the immune system may be due, at least in part, to localized inhibition or regulation of normal lymphocyte and/or macrophage functions within the gonads. In the testis, both steroidal and non-steroidal products of the Leydig cells, including androgens, endorphins, and inhibin-related proteins, have been implicated in mediating this activity. In turn, a number of immune cell cytokines affect steroidogenic cell function in vitro. The studies described in this paper indicated that [3H]-thymidine incorporation by adult rat thymocytes in vitro was inhibited by conditioned medium collected from short-term incubations of Percoll-purified adult rat Leydig cells, but stimulated by testicular interstitial fluid and by conditioned medium collected from short-term incubations of adult rat seminiferous tubules. The factors responsible for these effects on thymocyte function appeared to be of large molecular weight, as they were retained by ultrafiltration membranes with exclusion limits of 10,000 or 30,000 daltons. It is hypothesized that an 'immunosuppressive' mechanism, principally mediated by non-steroidal factors secreted by the steroidogenic cells of the gonadal interstitial tissue, exists within the gonads in order to prevent activation of the immune system by germ cell antigens and growth factors associated with germ cell proliferation and differentiation. This mechanism probably acts in parallel with normal antigen-specific tolerance mechanisms operating at the gonadal level. As immune responses to germ cells are believed to be a significant causative factor in infertility, particularly in men, this represents an important area for further study.

Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies

2012 ◽  
Vol 86 (7) ◽  
pp. 1137-1151 ◽  
Author(s):  
Christoph L. Klein ◽  
Karin Wiench ◽  
Martin Wiemann ◽  
Lan Ma-Hock ◽  
Ben van Ravenzwaay ◽  
...  
Keyword(s):  
Hazard Identification ◽  
Short Term

Drug Sensitivity of Different Tumor Lesions from the Same Patient Evaluated by a Short-Term Assay

1988 ◽  
Vol 74 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Nadia Zaffaroni ◽  
Rosella Silvestrini ◽  
Ornella Sanfilippo ◽  
Maria Grazia Daidone ◽  
Giorgio Bolis ◽  
...  
Keyword(s):  
Germ Cell ◽  
Clinical Response ◽  
Strong Association ◽  
Short Term ◽  
Agreement Rate ◽  
Testicular Tumors ◽  
Primary Tumors ◽  
Response To Chemotherapy ◽  
Synchronous Metastases

A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p < 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p < 0.01), but not to that of the primary tumor.

Detection of vital germ cell tumor cells in short-term cell cultures of primary tumors and of retroperitoneal metastasis ?Clinical implications

1997 ◽  
Vol 25 (2) ◽  
pp. 121-124 ◽  
Author(s):  
T. Otto ◽  
S. Virchow ◽  
C. Fuhrmann ◽  
F. Steinberg ◽  
C. Streffer ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Cells ◽  
Germ Cell Tumor ◽  
Cell Cultures ◽  
Cell Tumor ◽  
Clinical Implications ◽  
Short Term ◽  
Primary Tumors
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