Cancer gene therapy I: genetic intervention strategies
Nicholas R. Lemoine, David N. Cooper in Gene Therapy, 2020
The aim of cancer treatments is to destroy as much of the malignancy as possible without damaging normal tissue. This chapter reviews some of the gene therapy strategies that are being developed for the treatment of cancer together with a consideration of how genetic intervention could be used in the context of the hereditary predisposition syndromes. The majority of cancer gene therapy protocols have concentrated on the tumour suppressor gene, TPS3. Mutations in this gene have been implicated in several cancers including retinoblastoma, prostate carcinoma, osteosarcoma, soft-tissue sarcoma, breast carcinoma and small lung carcinoma. From the data presented so far, it appears that the Genetic prodrug activation therapy system is the most effective of those reviewed for the treatment of cancer. Somatic gene therapy involves the insertion of genes into the diploid cells of an individual where the genetic material is not passed onto the subject’s progeny.
Summary and Development of a New Approach to Senescence
Nate F. Cardarelli in The Thymus in Health and Senescence, 2019
Hayflick’s cell population doubling studies in vitro indicate that normal cells have some sort of internal regulation whose changes might be associated with senescence. Transformed cells escape the Hayflick limitation. Considerable evidence has been presented indicating a pineal-thymus axis as an effector of senescence. The popular view that hard radiation is detrimental to health is seldom tempered with the recognition that dosage level is critical. Therapeutic X-radiation directed at the hypothalamus of children inevitably leads to precocious puberty. Cells from patients with progeria, ataxia telangiectasia, and retinoblastoma were found to be more sensitive to hard radiation than normal cells. Physiological systems responding to radiation input, presumably through alteration of the biological clock, include both the immune and the endocrine systems. Endocrine response is probably centered on the hypothalamus and involves various releasing hormones, such as thyrotropin releasing hormone.
Cancer genetics and genomics
Tom Strachan, Andrew P Read in Human Molecular Genetics, 2018
The selection in tumors operates over many generations of cells, but all within the lifetime of a single host individual. Specific point mutations in RAS genes are frequently found in cells from a variety of tumors including colon, lung, breast, and bladder cancers. The best-known example of activation by a translocation that creates a novel chimeric gene is the Philadelphia chromosome. An early landmark in the people understanding of tumor suppressor genes was Knudson's work in 1971 on retinoblastoma. Compared to adult cancers, embryonal tumors show strikingly little evidence of the usual extensive genetic instability. Tumor suppressor genes may be silenced by deletion (reflected in loss of heterozygosity) or by point mutations, but a very common third mechanism is methylation of the promoter. The people's new understanding of driver mutations in cancer has stimulated an intense effort to develop agents to target the specific molecules or pathways that drive tumor development.
LncRNA NKILA Inhibits Retinoblastoma by Downregulating lncRNA XIST
Published in Current Eye Research, 2019
Xueman Lyu, Yunqing Ma, Fei Wu, Ling Wang, Lina Wang
Purpose: Although retinoblastoma is rare but can be deadly in some severe cases. To find novel therapeutic targets for retinoblastoma, we explored the potential role of lncRNA NKILA in retinoblastoma. Results: We found that, comparing to healthy controls, NKILA was downregulated, while lncRNA XIST was upregulated in plasma of retinoblastoma patients and they were inversely correlated. Downregulation of NKILA distinguished early-stage patients from healthy controls. Overexpression of lncRNA NKILA mediated the downregulation of XIST in retinoblastoma cells, while XIST overexpression failed to significantly affect NKILA. Overexpression of NKILA resulted in decreased, while XIST overexpression resulted in increased proliferation, migration and invasion rates of retinoblastoma cells. In addition, rescue experiment showed that XIST overexpression attenuated the effects of NKILA overexpression on cancer cell behaviors. Conclusions: Therefore, NKILA inhibits retinoblastoma possibly by downregulating XIST, but the causality has not been fully validated.
A case of retinoblastoma metastasizing to the mandible and review of literature
Published in CRANIO®, 2016
Seigo Ohba, Akihiko Tanizawa, Hitoshi Yoshimura, Shinpei Matsuda, Yoshiaki Imamura, Kazuo Sano
Objectives: The aim of this case report and review was to determine the characteristics of retinoblastoma. Methods: One case report was introduced along with previous reports on retinoblastoma metastasizing to the mandible. Results: Sixteen cases from 14 reports were included in this study. Including the present case, 11 of 16 patients died within 8 months. Discussion: Retinoblastoma rarely metastasizes to the mandible. However, metastasis to other organs should be considered, and specialists should be consulted if retinoblastoma metastasis to the mandible is observed. Moreover, it is necessary to follow up patients after multidisciplinary therapy is completed, because subsequent complications of the teeth and jawbones associated with therapy could occur.
Orbital Retinoblastoma in an Adult
Published in Orbit, 2013
Bhavna Chawla, Maya Hada, Seema Kashyap, Sameer Bakhshi
Purpose: Retinoblastoma is usually seen in children before 5 years of age. We report an unusual case of retinoblastoma in an adult who presented to us with an orbital mass. Methods: A 24 year-old-male presented to our centre with a history of protrusion of the right eye for 6 months, and associated loss of vision. Ultrasonography B-scan revealed an intraocular mass with calcification and MRI of the orbits showed extra-ocular spread. An incisional biopsy was taken from the orbital mass. Results: On biopsy, histopathologic features and immunohistochemical stains were consistent with retinoblastoma. Conclusion: To our knowledge, this is the first report of retinoblastoma presenting as an orbital mass in adulthood and highlights the importance of considering this tumour in the differential diagnosis of an intraocular mass with orbital extension in an adult patient.
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