The Morphologic Assessment of Rectal Neuroendocrine Tumors

AbstractBackground and aimsThe histopathologic features of rectal neuroendocrine tumors (NETs), including size, lymphovascular invasion, invasion of proper muscle, and mitotic rate, have a limited role to play in determining a treatment plan preoperatively. We aimed to investigate the morphologic parameters associated with metastasis, and to evaluate their predictive value.MethodsBetween January 2000 and May 2011, the medical records and endoscopic findings of 468 patients presenting with rectal NETs at the Samsung Medical Center were analyzed retrospectively. All tumors were classified according to size and endoscopic features such as color, shape, contour, and surface change.ResultsTwenty-one of the 468 patients (4.5%) with rectal NETs had lymph node (LN) metastasis and 11 patients (2.4%) had distant metastasis. Risk factors for metastasis included tumor size (≥10mm in diameter), hyperemic change, polypoid lesions, irregular contours, and surface ulceration (p=0.000). Independent risk factors that were predictive of metastasis on multivariate analysis included tumor size (≥10mm in diameter), hyperemic change, and surface ulceration. As the number of independent risk factors for metastasis increased, the risk of metastasis rose.ConclusionsEndoscopic features such as hyperemic change, polypoid lesions, irregular contours, and surface ulcers with tumor size ≥10mm in diameter are associated with metastasis in rectal NETs. In particular, atypical endoscopic features including hyperemic change, and surface ulcer with tumor size ≥10mm in diameter may help to predict the risk of metastasis of rectal NETs

Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation

Labisia pumila (Myrsinaceae), known as "Kacip Fatimah," has been used by many generations of Malay women to induce and facilitate child birth as well as a post partum medicine. However, its topical application on skin has not been reported yet. In this study, we have focused on the anti-photoaging effects of L. pumila. Extract of L. pumila was first analyzed for their antioxidant activities using DPPH (2,2-diphenyl-1-picrylhydrazyl) since UV irradiation is a primary cause of reactive oxygen species (ROS) generation in the skin. The 50% free radical scavenging activity (FSC(50)) of L. pumila extract was determined to be 0.006%, which was equal to that produced by 156 microM ascorbic acid. TNF-alpha and cyclooxygenase (COX-2) play a primary role in the inflammation process upon UV irradiation and are known to be stimulated by UVB. Treatment with L. pumila extract markedly inhibited the TNF-alpha production and the expression of COX-2. Decreased collagen synthesis of human fibroblasts by UVB was restored back to normal level after treatment with L. pumila extract. On the other hand, the enhanced MMP-1 expression upon UVB irradiation was down regulated by L. pumila extract in a dose-dependent manner. Furthermore, treatment of normal keratinocytes with L. pumila extract attenuated UVB-induced MMP-9 expression. These results collectively suggest L. pumila extract has tremendous potential as an anti-photoaging cosmetic ingredient

Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

Serum 25-hydroxyvitamin D levels and risk of colorectal cancer:an age-stratified analysis

Background and aims: the role of circulating 25-hydroxyvitamin D (25(OH)D) in prevention of early-onset colorectal cancer (CRC) in young adults under 50 years is uncertain. We evaluated the age-stratified associations (&lt;50 vs. ≥50 years) :circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults.Methods: our cohort study included 236,382 participants (mean [standard deviation] age, 38.0 [9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as follows: &lt;10, 10–20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders.Results: during the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5–7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged &lt;50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43–0.86) and 0.41 (0.27–0.63) for 25(OH)D 10-19 and ≥20 ng/mL, respectively, with respect to the reference (&lt;10 ng/mL) (p for trend &lt;0.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared to younger individuals. Conclusions: serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease. <br/