Deletions of p15 and p16 in schistosomal bladder cancer correlate with transforming growth factor-α expression

c-KIT Positive Schistosomal Urinary Bladder Carcinomas are Frequent but Lack KIT Gene Mutations

“…This has led to numerous studies in an effort to understand the cytogenetic and molecular biology of Schistosomal SCCs. One of these studies demonstrated mutations in exons 5-8 of the p53 gene (Warren et al, 1995) while another study demonstrated alterations in the P15 and P16 genes (Swellam et al, 2004). To the best of our knowledge, the current study is the first to evaluate the expression and mutation of c-KIT in Schistosomal SCCs.…”

Tumor Suppressor Gene p16/INK4A/CDKN2A and Its Role in Cell Cycle Exit, Differentiation, and Determination of Cell Fate

“…Concomitant overexpression of p16 and p73 has oncogenic potential and affects the development and growth of breast carcinomas (Garcia et al, 2004). Alteration of p15 and p16 expression and overexpression of TGF- are found frequently in schistomal bladder cancers and squamous cell carcinomas (Swellam et al, 2004). Loss of p16 expression has prognostic value in predicting recurrence-free probability in patients affected by low-grade urothelial bladder cancer (Bartoletti et al, 2007).…”

“…Deletion of the 9p21 region encoding the p16-INK4A/p14ARF/p15 tumor suppressor loci in humans results in tumor formation in a wide range of tissues (Kamb et al, 1994;Kleihues et al, 1994;Packenham et al, 1995). Loss of heterozygosity (Swellam et al, 2004), loss of homozygosity (Ranade et al, 1995;Quelle et al, 1997), and hypermethylation of the promoter (Herman et al, 1997) in the 9p21 region are all important mechanisms which have been shown to result in loss of p16 expression and promote p16-related neoplasms. Hyper-methylation of the p16 promoter region appears to occur early in neoplastic transformation before development of tumorigenicity in rat respiratory epithelium (Yamada et al, 2010).…”

“…p53 and p16 are thought to work via two independent pathways of growth suppression, but both of them are important in suppressing malignant transformation (Gruis et al, 1995). p16 gene deletions are associated with, and appear permissive for, late-stage, high-grade cancers such as; melanoma, bladder cancer, schistosomal bladder cancer, esophageal cancer, breast cancer, and glioblastoma (Gruis et al, 1995;Izumoto et al, 1995;Zhou et al, 1995;Swellam et al, 2004;DeInnocentes et al, 2009). Deletion of the 9p21 region encoding the p16-INK4A/p14ARF/p15 tumor suppressor loci in humans results in tumor formation in a wide range of tissues (Kamb et al, 1994;Kleihues et al, 1994;Packenham et al, 1995).…”

The effectiveness of retinoic acid treatment in bladder cancer: Impact on recurrence, survival and TGFα and VEGF as end-point biomarkers.

“…Therefore, modulation of EGFR/ TGFα expression is significant prognostic end-point biomarkers in bladder cancer and a major strategy for the anticancer and chemopreventive agents in bladder cancer. [9][10][11][12] Obstruction of VEGF and TGFα pathways inhibited the growth and metastasis of human TCC orthografts and potentiated chemotherapeutic agents, in part by inhibiting proliferation, angiogenesis, and inducing apoptosis. [13][14] Retinoids act pharmacologically to restore differentiation and inhibit growth in certain premalignant and malignant cells in vitro and in vivo, being the primary line of treatment for (acute myeloplastic) leukemia and several clinical trials were conducted including…”