PCNA levels in neuroblastoma are increased in tumors with an amplified N- myc gene and in metastatic stage tumors

N- myc oncogene amplification in neuroblastoma has been found to be significantly associated with advanced stage disease and tumor progression. However, there is a lack of data on tumors, regarding the relationship between N- myc gene amplification and proliferation activity. Proliferating cell nuclear antigen (PCNA) is a proliferation-induced 36 kD nuclear protein that is the auxiliary component of DNA polymerase δ. PCNA levels in tissues have been found to correlate with proliferative activity. We have examined PCNA levels in neuroblastomas in relation to N- myc gene amplification and tumor stage. Statistically, significantly higher levels of PCNA were observed in tumors with an amplified N- myc gene relative to tumors with a single gene copy. The highest levels of PCNA were observed in advanced stage tumors with an amplified N- myc gene. Treatment of neuroblastoma cells in culture with retinoic acid, which induces differentiation, resulted in a substantial decrease in PCNA. Our results suggest that PCNA levels may reflect differences in proliferative activity between neuroblastomas, related to stage of the disease and to N- myc gene copy number.[/p ]Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42581/1/10585_2004_Article_BF00880069.pd

Metastasis Suppressors and the Tumor Microenvironment

The most dangerous attribute of cancer cells is their ability to metastasize. Throughout the process of metastasis, tumor cells interact with other tumor cells, host cells and extracellular molecules. This brief review explores how a new class of molecules – metastasis suppressors – regulate tumor cell–microenvironmental interactions. Data are presented which demonstrate that metastasis suppressors act at multiple steps of the metastatic cascade. A brief discussion for how metastasis suppressor regulation of cellular interactions might be exploited is presented

Test of insulin resistance in nondiabetic and streptozotocin-induced diabetic rats using glycosylated hemoglobin test and other interventions

Type 2 diabetes is common globally. Pioglitazone (PGZ) is an oral TZD antidiabetic, whereas chromium-picolinate (Cr-PL) and Cr-glucose tolerance factor (Cr-GTF) are useful type 2 diabetes mellitus (T2DM) supplements. Cr-PL/GTF antioxidants cure T2DM. They may fail in diabetes with or without insulin-sensitizing medications. It examined how Cr-PL, Cr-GTF, PGZ, and their combination affected glucose, glycosylated hemoglobin, insulin, and HOMA-IR. Sixty-three adult Sprague-Dawley rats (220–300 g) were selected, and nine rats were randomly assigned to a normal nondiabetic group. In contrast, 54 rats were randomly split into 9 rats per each of the 6 major groups and injected intraperitoneally with 40 mg/kg STZ to induce T2DM. Rats were administered PGZ = 0.65 mg/kg (rat weight)/day, Cr-PL = 1 mg/kg, Cr-GTF = 1 mg/kg, and their combinations (PGZ + Cr-PL and Cr-GTF) daily for 6 weeks per intervention. The PGZ + Cr-PL and PGZ + Cr-GTF groups had substantially lower insulin levels than the PGZ group (13.38 ± 0.06, 12.98 ± 0.19 vs. 14.11 ± 0.02, respectively), with the PGZ + Cr-GTF group having the lowest insulin levels (12.98 ± 0.19 vs. 14.11 ± 0.02, 13.38±0.06, respectively). Intervention substantially reduced HOMA-IR in the PZ + Cr-PL and PZ + Cr-GTF groups compared to PGZ (7.49 ± 0.04, 6.69 ± 0.11 vs. 8.37 ± 0.04, respectively). This research found that combining PGZ with Cr-GTF resulted in considerably lower HOMA-IR levels than the PGZ and Cr-PL groups (6.69 ± 0.11 vs. 8.37 ± 0.04, 7.49 ± 0.04, respectively). Both Cr-PL and Cr-GTF may control T2DM. Both Cr complexes improved T2DM biomarkers more than the control diabetic group without medication. PGZ alone and PGZ + Cr-PL had less pharmacological synergy than Cr-GTF and PGZ in altering insulin and HOMA-IR blood levels. These encouraging discoveries need more study