Skip metastases occur in a minority of patients with PTMC. We recommend, therefore, that preoperative studies in patients suspected of having PTMC focus not only on nodes in the central compartment but also lateral cervical nodes since the information obtained would guide the extent of surgery.

Disruption of the function of tumor suppressor proteins occasionally can be dependent on their subcellular localization. In about 40% of the breast cancer tissues, p53 is found in the cytoplasm as opposed to the nucleus, where it resides in normal breast cells. This means that the regulation of subcellular location of p53 is an important mechanism in controlling its function. The transport factors required for the nuclear export of p53 and the mechanisms of their nuclear export have been extensively characterized. However, little is known about the mechanism of nuclear import of p53. p53 contains putative nuclear localization signals (NLSs) which would interact with a nuclear transport factor, importin ␣. In this report we demonstrate that importin ␣ binds to NLSI in p53 and mediates the nuclear import of p53. Reverse transcriptase-polymerase chain reaction and sequencing analyses showed that a truncated importin ␣ deleted the region encoding the putative NLS-binding domain of p53, suggesting that it could not bind to NLSs of p53 proteins. Binding of importin ␣ to p53 was confirmed by using yeast two-hybrid assay. When expressed in CHO-K1 cells, the truncated importin ␣ predominantly localized to the cytoplasm. In truncated importin ␣ expressing cells, p53 preferentially localized to cytoplasmic sites as well. A significant increase in the p21 waf1/cip1 mRNA level and induction of apoptosis were also observed in importin ␣ overexpressing cells. These results strongly suggest that importin ␣ functions as a component of the NLS receptor for p53 and mediates nuclear import of p53.p53 is a tumor suppressor gene and various p53 gene mutations are found in over 50% of all human cancers (1). Although inactivation of tumor suppressor proteins is generally thought to originate in their genetic mutations, disruption of their function can occasionally be independent of such mutations. Moll et al. (2) have reported that about 37% out of 27 samples of breast cancer tissues showed cytoplasmic localization of wild-type p53, resulting in inhibition of normal p53 function (2). Nuclear exclusion of wild-type p53 has also been reported in neuroblastoma and colon carcinoma cells (3, 4). In another study, wild-type p53 was located in the cytoplasm of human cervical carcinoma cell lines with integrated human papillomavirus-18 or -16 (5). In colon carcinoma, cytoplasmic accumulation of p53 correlates with unfavorable prognosis (4). These data indicate that the regulation of p53 subcellular location is an important mechanism in controlling p53 function.In eukaryotic cells, the nucleus is separated from the cytoplasm by the nuclear envelope. This spatial segregation requires a nuclear transport system to correctly import or export nuclear components at the proper time. The prototype of the nuclear transport signal is the classical nuclear localization signal (NLS), 1 and nuclear import of proteins bearing an NLS is dependent on two cellular factors termed importin ␣ and importin ␤ (6 -11). The initial cytoplasmic event in NLS-dependent...

AIM:To determine the association of hOGG1 (8-oxoguanine glycosylase I, OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors. METHODS:A case-control study with 125 colon cancer cases and 247 controls was conducted. RESULTS:There was no major difference in Ser326Cys genotype distribution between cases and controls. The meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95 % confidence interval; CI=1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR=4.31, 95 % CI=1.64-11.48), but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/ Cys carriers. The OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR=2.75, 95 % CI=1.07-7.53) but not in Ser/Ser or Ser/ Cys carriers. CONCLUSION:These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall, but the Cys/ Cys genotype may alter the impact of some environmental factors on colon cancer development.Kim JI, Park YJ, Kim KH, Kim JI, Song BJ, Lee MS, Kim CN, Chang SH. hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol 2003; 9(5): 956-960

We present a 53-year-old man with a crystalline lens that spontaneously dislocated anteriorly with corneal touch and secondary glaucoma. A dry anterior vitrectomy and partial intercapsular lensectomy were performed using a limbal approach to control intraocular pressure (IOP) and decrease the lens volume. The lens capsule was gently separated from the corneal endothelium with viscoelastic material, after which a bimanual lensectomy was performed with a vitrectomy probe and a phacoemulsification microflow tip. The risk for expulsive choroidal hemorrhage, which can occur during large-incision, open-chamber surgery; a sudden IOP decrease; and significant damage to the corneal endothelium were avoided with this technique. After secondary intraocular lens scleral fixation, the final visual acuity was 20/25.

In PTC patients ≥45 years of age, a higher BMI was associated with more aggressive tumor features, such as lymph node metastasis, lymphatic invasion, and tumor multiplicity.

Glioblastoma stem cells (GSCs) are a subpopulation of highly tumorigenic and stem-like cells that are responsible for resistance to conventional therapy. Bcl-2-intreacting cell death suppressor (BIS; also known as BAG3) is an anti-apoptotic protein that is highly expressed in human cancers with various origins, including glioblastoma. In the present study, to investigate the role of BIS in GSC subpopulation, we examined the expression profile of BIS in A172 and U87-MG glioblastoma cell lines under specific in vitro culture conditions that enrich GSC-like cells in spheres. Both BIS mRNA and protein levels significantly increased under the sphere-forming condition as compared with standard culture conditions. BIS depletion resulted in notable decreases in sphere-forming activity and was accompanied with decreases in SOX-2 expression. The expression of STAT3, a master regulator of stemness, also decreased following BIS depletion concomitant with decreases in the nuclear levels of active phosphorylated STAT3, while ectopic STAT3 overexpression resulted in recovery of sphere-forming activity in BIS-knockdown glioblastoma cells. Additionally, immunoprecipitation and confocal microscopy revealed that BIS physically interacts with STAT3. Furthermore, BIS depletion increased STAT3 ubiquitination, suggesting that BIS is necessary for STAT3 stabilization in GSC-like cells. BIS depletion also affected epithelial-to-mesenchymal transition-related genes as evidenced by decrease in SNAIL and MMP-2 expression and increase in E-cadherin expression in GSC-like cells. Our findings suggest that high levels of BIS expression might confer stem-cell-like properties on cancer cells through STAT3 stabilization, indicating that BIS is a potential target in cancer therapy.

Endocrine therapy is provided to all patients with estrogen receptor (ER)-positive breast cancer, but only a subset of them derives clinical benefit. The discovery of ERβ and its five isoforms added another layer of complexity in the regulation of estrogen activity in breast cancer cells. Two large retrospective studies showed conflicting results with regard to the prognostic value of the different ERβ isoforms in patients treated with tamoxifen in an adjuvant setting. This study tested the hypothesis that ERβ1 and, or ERβ2 are correlated with clinical outcome. We identified patients with breast cancer who had undergone surgery at Bucheon St. Mary's Hospital, the Catholic University of Korea, between January 2004 and March 2006. We evaluated 101 consecutive cases for ERβ1 and ERβ2 expression using immunohistochemical staining and obtained other clinicopathology by reviewing medical records. ERβ1 was expressed in 81.2% (79 of 97) and ERβ2 was expressed in 50.5% (51 of 101) of primary breast cancer tissues. Disease-free survival (DFS) and overall survival (OS) of patients with cancers expressing ERβ2 was significantly worse. Moreover, in subgroup analysis according to the tamoxifen treatment, ERβ2 expression was significantly associated with shorter DFS of tamoxifen-treated patients. This study indicates that breast cancer with ERβ2 expression was associated with worse DFS and OS, especially in tamoxifen treated patients. Our results suggest a role for ERβ2 as an independent prognostic marker and might serve as a new therapeutic target.

The clinical relevance of regulatory T cell (Treg) infiltration in breast cancer (BC) remains controversial, and no recent meta-analysis has been published on this subject. Our aim was to identify the precise relationship between Tregs and the prognosis and clinic-pathological features of BC. Eligible articles were identified with a MEDLINE database search over a period up to March 2015. Our meta-analysis was performed using STATA software 11.0 and Review Manager 5.3. The correlations between Treg infiltration and clinico-pathological features and BC prognosis were analyzed. Subgroup and sensitivity analyses, as well as meta-regression, were conducted. Eighteen published studies (including 8,562 patients) were eligible. Overall survival (OS) and disease-, recurrence-, and progression-free survival (DFS/RFS/PFS) were correlated with Treg infiltration (OR=2.03 (95% CI, 1.40-2.95; P=0.000) and 1.48 (95% CI, 1.00-2.19; P=0.050), respectively), including 3-, 5-, and 10-year mortality rates. In addition, low Treg infiltration was present in estrogen receptor (ER)-positive tumors (P=0.000), progesterone receptor (PR)-positive tumors (P=0.003), Her2-negative tumors (P=0.000) and histological grade I/II tumors (P=0.001). No publication bias was observed with the exception of OS. Subgroup analysis suggested that the mortality rate of the high Treg infiltration subgroup was increased compared with the low Treg infiltration subgroup among ER-positive patients. Treg infiltration indicated a poorer prognosis for BC and is related to ER, PR, and Her2 status and histological grade. Thus, Treg infiltration could help predict outcomes and guide clinical therapy.