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Updated: Sep 20, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Regression of upper gastric cancer in mice by FHIT gene delivery
Hideshi Ishii1, Nicola Zanesi, Andrea Vecchione
1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
Fhit expression is reduced in most cancers, and Fhit replacement by FHIT expression viruses in lung, esophageal, pancreatic, and cervical cancers induces apoptosis in the cancer cells. Mice carrying one or two inactivated Fhit alleles are hypersensitive to development of N-nitrosomethylbenzylamine (NMBA)-induced forestomach tumors. In the present study, we investigated the kinetics and mechanism of tumor reversal and intervention by oral delivery of FHIT expression viruses. Tumor analysis showed that: a) by 37 days post-NMBA, control mice showed approximately 7 tumors and by 84 days approximately 10 tumors/forestomach; b) mice receiving FHIT virus at 2 or 42 days post-NMBA showed significantly reduced tumor burdens; c) Fhit was still expressed at 82 days postinfection; d) control viral infection had no effect on tumor development; and e) reduced Bcl2, increased Bax expression, and increased TUNEL-positive apoptotic nuclei characterized the restored epithelia of FHIT transduced forestomachs. Thus, FHIT viral gene delivery prevents or retards development of carcinogen-induced forestomach tumors and reverses development of established tumors by 60-70% through an apoptotic pathway. This dramatic reduction in tumor burden emphasizes the efficacy of targeting the FHIT apoptotic pathway for tumor eradication.
Insights
FHIT gene therapy using viral vectors significantly reduces carcinogen-induced forestomach tumors in mice. Oral delivery of FHIT expression viruses reverses established tumors by inducing apoptosis, highlighting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Reduced Fhit expression is common in various cancers.
- FHIT gene replacement via viral vectors induces apoptosis in cancer cells.
- Mice with inactivated Fhit alleles exhibit hypersensitivity to carcinogen-induced tumors.
Purpose of the Study:
- Investigate the kinetics and mechanism of tumor reversal and intervention using oral FHIT gene delivery.
- Evaluate the efficacy of FHIT viral gene therapy in a mouse model of forestomach tumors.
Main Methods:
- Oral administration of FHIT expression viruses to mice with N-nitrosomethylbenzylamine (NMBA)-induced forestomach tumors.
- Tumor burden analysis at different time points post-carcinogen exposure.
- Assessment of Fhit expression, apoptosis markers (Bcl2, Bax, TUNEL), and viral infection effects.
Main Results:
- FHIT virus treatment significantly reduced tumor burden compared to controls.
- FHIT expression persisted for at least 82 days post-infection.
- FHIT gene delivery led to reduced Bcl2, increased Bax expression, and increased apoptotic nuclei.
- Control viral infection did not impact tumor development.
Conclusions:
- FHIT viral gene delivery effectively prevents and reverses carcinogen-induced forestomach tumors.
- The mechanism involves inducing apoptosis in tumor cells via the FHIT pathway.
- Targeting the FHIT apoptotic pathway shows significant potential for tumor eradication.
