Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include BRCA1, BRCA2, p53, PTEN, CHEK2 and ATM. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.
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PMID:Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: evidence that they exert tumoricidal effects via tumor tropism (review). 2273 97

Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCCs) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCCs, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. In contrast, in HPV-negative OSCCs, T>C substitutions in the sequence context 5'-ATN-3' correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCCs. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1, and NFKBIA Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon (IFN) and nuclear factor kappa B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCCs, in contrast to their gains in HPV-negative OSCCs. High-ranking variant allele fractions implicated ZNF750, PIK3CA, and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.
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PMID:Human papillomavirus and the landscape of secondary genetic alterations in oral cancers. 3056 11