acyclovir and Testicular-Neoplasms

The frequencies of reactivated disease due to varicella-zoster virus (VZV) in immunocompromised patients were determined by enzyme-linked immunosorbent assay for antibody and also by the lymphocyte proliferation response to VZV antigen. Subclinical reactivations were as common as classical herpes zoster in all patient groups. Among bone marrow transplant (BMT) recipients, 36% developed herpes zoster and 26%, a subclinical reactivation. The corresponding frequencies for patients with leukemia during induction therapy were 5% and 10%; in renal transplant recipients, 0% and 26%; and in patients with seminoma, 0% and 6%, respectively. Subclinical reactivation of VZV thus appears to be a common finding in severely immunocompromised patients. A regained lymphocyte proliferation response to VZV antigen is a sensitive indicator of subclinical reactivation of VZV in BMT recipients. None of 19 BMT recipients with subclinical disease due to VZV later developed clinical reactivation of VZV. Acyclovir given as prophylaxis against infection with herpes simplex virus reduced the number of clinical and subclinical reactivations of VZV during treatment in BMT recipients, but not thereafter.

Topics: Acyclovir; Antibodies, Viral; Antigens, Viral; Bone Marrow Transplantation; Chickenpox; Dysgerminoma; Graft vs Host Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Immune Tolerance; Immunoglobulin G; Kidney Transplantation; Leukemia; Lymphocyte Activation; Male; Recurrence; Testicular Neoplasms

To develop a new toxic gene therapy using the tissue-specific human chorionic gonadotropin-beta (hCG-beta) promoter for testicular cancer. Although most patients presenting with disseminated testicular tumor are cured through the use of chemotherapy with or without surgery, those patients with relapse after initial therapy present a difficult clinical problem. The serum tumor marker hCG-beta is frequently elevated in patients with testicular cancer, and the pretreatment and post-treatment levels of serum hCG-beta are highly predictive of treatment outcome.. Human testicular embryonal carcinoma cell line, NEC 8, a human prostate cancer cell line, PC-3, and a human bladder cancer cell line, WH, were used in this study. A transient expression experiment was used to analyze the activity of a 729-bp hCG-beta promoter in all three cell lines. A recombinant adenovirus carrying thymidine kinase (Ad-hCG-beta-TK) under control of the hCG-beta promoter was generated. The tissue-specific activity of Ad-hCG-beta-TK was tested in vitro and in vivo.. The hCG-beta promoter had significantly greater activity in the hCG-beta-producing cell line (NEC 8) than in the non-hCG-beta-producing cell lines (PC-3 and WH). In vitro, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 growth but not PC-3 or WH cell growth. In vivo, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 subcutaneous tumor growth in nude mice.. In this study, we explored the possibility of developing a new therapeutic agent to target and induce the killing of testicular germ cell tumor selectively by using tissue-specific hCG-beta promoters.

Topics: Acyclovir; Adenoviridae; Animals; Biomarkers, Tumor; Carcinoma; Carcinoma, Embryonal; Cell Line, Tumor; Chorionic Gonadotropin, beta Subunit, Human; Enzyme Inhibitors; Genes, Transgenic, Suicide; Genetic Therapy; Genetic Vectors; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins; Prodrugs; Promoter Regions, Genetic; Prostatic Neoplasms; Recombinant Fusion Proteins; Salvage Therapy; Testicular Neoplasms; Thymidine Kinase; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays

We have previously produced transgenic (TG) mice expressing the mouse inhibin alpha-subunit promoter/Simian virus 40 T-antigen (Inhalpha/Tag) fusion gene. The mice develop gonadal somatic cell tumors at the age of 5-7 months; the ovarian tumors originate from granulosa cells, and those of the testes from Leydig cells. In the present study another TG mouse line was produced, expressing under the same inh-alpha promoter the herpes simplex virus thymidine kinase gene (Inhalpha/TK). Crossbreeding of the two TG mouse lines resulted in double TG mice (Inhalpha/TK-Inhalpha/Tag), which also developed gonadal tumors. The single (Inhalpha/Tag) and double TG (Inhalpha/TK-Inhalpha/Tag) mice, both bearing gonadal tumors, were treated at the age of 5.5-6.5 months with ganciclovir (GCV, 150 mg/kg body weight twice daily i.p.) for 14 days, or with aciclovir (ACV, 300-400 mg/kg body weight per day perorally) for 2 months. During GCV treatment, the total gonadal volume including the tumor, decreased in double TG mice by an average of 40% (P<0.05), while in single TG mice, there was a concomitant increase of 60% in gonadal size (P<0.05). GCV was also found to increase apoptosis in gonads of the double TG mice. Peroral treatment with ACV was less effective, it did not reduce significantly the gonadal volume. We also analyzed the in vitro efficacy of ACV and GCV treatments in transiently HSV-TK-transfected KK-1 murine granulosa tumor cells, originating from a single-positive Inhalpha/Tag mouse. GCV proved to be more effective and more specific than ACV in action. These results prove the principle that targeted expression of the HSV-TK gene in gonadal somatic cell tumors is potentially useful for tumor ablation by antiherpes treatment. The findings provide a lead for further development of somatic gene therapy for gonadal tumors.

Topics: Acyclovir; Animals; Antigens, Polyomavirus Transforming; Antiviral Agents; Apoptosis; Breeding; Female; Ganciclovir; Gene Expression; Genetic Therapy; Granulosa Cell Tumor; Inhibins; Leydig Cell Tumor; Male; Mice; Mice, Transgenic; Ovarian Neoplasms; Promoter Regions, Genetic; RNA, Messenger; Simplexvirus; Testicular Neoplasms; Thymidine Kinase

Topics: Acyclovir; Anilides; Cytomegalovirus Infections; Flutamide; Ganciclovir; Humans; Ifosfamide; Male; Methadone; Opioid-Related Disorders; Professional Staff Committees; Prostatic Neoplasms; Testicular Neoplasms