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Background: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. Methods: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. Results: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P =0.019 and 6.90 vs 5.49 months, P =0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS ( P =0.467 and P =0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. Conclusions: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

Higher expression of human telomerase reverse transcriptase (hTERT) and subsequent activation of telomerase occur during cellular immortalization and are maintained in cancer cells. To understand the mode of hTERT expression in cancer cells, we identified cancer-specific trans -regulatory proteins that interact with the hTERT promoter, using the promoter magnetic precipitation assay coupled with mass spectrometry. The identified proteins include MutS homolog 2 (MSH2), heterogeneous nuclear ribonucleoprotein (hnRNP) D, hnRNP K and grainyhead-like 2 (GRHL2). We noticed a higher expression of these proteins in human oral squamous cell carcinoma (OSCC) cells than in normal cells, which do not exhibit telomerase activity. Knockdown of MSH2, hnRNP D and GRHL2 resulted in a notable reduction of the hTERT promoter activity in tested cancer cells. Silencing of the above genes resulted in a significant reduction of the telomerase activity in OSCC cells. Interestingly, among the four identified genes, silencing of GRHL2 was essential in reducing telomerase activity and viability of tested cancer cells. These results suggest a possible role of GRHL2 in telomerase activation during cellular immortalization.

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Telomerase activity in human cells closely correlates with the expression of its catalytic subunit, telomerase reverse transcriptase ( hTERT ). Previously, we reported the lack of telomerase activity in normal human oral fibroblasts (NHOF) and the diminution of telomerase activity during senescence in normal human oral keratinocytes (NHOK). To investigate the underlying mechanisms of telomerase regulation in both cell types, we analysed the expression, promoter activity, and methylation status of the hTERT gene. The expression of hTERT mRNA diminished in senescent NHOK, but was not detected in NHOF at any stage of replication. An exogenous hTERT promoter was active in NHOF and in senescing NHOK, indicating that the lack of hTERT gene expression resulted from alteration of the endogenous hTERT promoter. Since methylation is involved in the silencing of numerous genes, we carried out DNA methylation assays. The assay revealed that the hTERT promoter was hypermethylated in NHOF and was gradually methylated during senescence in NHOK. Treatment of NHOF and senescent NHOK with the demethylating agent 5-aza-2′-deoxycytidine restored the expression of endogenous hTERT mRNA. Our results suggest that hypermethylation of the hTERT promoter plays a critical role in the negative regulation of telomerase activity in normal human oral cells.

A heuristic algorithm using new block strategy for the heterogeneous single and multiple containers loading problem (CLP) is proposed in this paper. In order to solve the single CLP, this algorithm fills unused spaces with the homogeneous load-blocks of identically oriented boxes and splits residual space into three child-spaces starting with an empty container. An initial container pattern is first built applying this approach recursively until all boxes are stowed or no unused spaces are left. And then, alternative container patterns are generated after replacing the load-blocks of the pattern-determining spaces in the initial container pattern with the alternative-blocks previously stored. Finally, an improvement procedure compares these alternatives with the initial container pattern to identify an improved container pattern. An algorithm for the multiple CLP uses the single CLP algorithm to generate an initial solution and uses improvement procedures to improve the initial solution. Numerical experiments with 715 test cases for the single CLP and 47 test cases for the multiple the CLP revealed the excellent performance of this algorithm.

A material property measurement system for steel sheets using laser-based ultrasonics was developed. The system consists of a pulsed Nd:YAG laser for ultrasonic generation and multi-channel interferometer coupled with a CW single frequency laser for ultrasonic detection. The system can measure the frequency of the S1 Lamb wave mode of zero group velocity (S1f) as well as the longitudinal resonance frequencies without ablative damage to the steel surface. It was confirmed that Poisson's ratio could be directly obtained by combining the measured S1f value and the longitudinal resonance frequencies. To evaluate the applicability of this system in an actual steel production setting, the system was installed in hot rolling pilot plant that produces steel samples. As a result, it was demonstrated that the system can measure dynamic changes in Poisson's ratio values within steel sheets, even in the hot rolling pilot plant environment. Material property data, such as Poisson's ratio, during the thin sheet production process will be very useful for manufacturing high value-added steel, such as sheets with uniform quality.

We recently identified Grainyhead-like 2 (GRHL2), a mammalian homolog of Grainyhead in Drosophila , to be a novel transcription factor that regulates hTERT gene expression and enhances proliferation of normal human epidermal keratinocytes (NHEK). In the current study, we show that GRHL2 impairs keratinocyte differentiation through transcriptional inhibition of the genes clustered at the epidermal differentiation complex (EDC), located at chromosome 1q21. Gene expression profiling and subsequent in vitro assays revealed consistent downregulation of EDC genes, for example, IVL , KRT1 , FLG , LCEs , and SPRRs , in NHEK expressing exogenous GRHL2. In vivo binding assay by chromatin immunoprecipitation revealed GRHL2 association at the promoter regions of its target genes, many of which belong to EDC. Exogenous GRHL2 expression also inhibited recruitment of histone demethylase Jmjd3 to the EDC gene promoters and enhanced the level of histone 3 Lys 27 trimethylation enrichment at these promoters. Survey of GRHL2 expression in human skin tissues demonstrated enhanced protein and mRNA levels in chronic skin lesions with impaired keratinocyte differentiation, for example, atopic dermatitis and psoriasis, compared with normal epidermis. These data indicate that GRHL2 impairs epidermal differentiation by inhibiting EDC gene expression through epigenetic mechanisms and support its role in the hyperproliferative skin diseases.

Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16 INK4A , a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16 INK4A /pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16 INK4A -independent pathways to regulate cellular proliferation during oral cancer progression.

Anatomical descriptions of the maxillary sinus are critical in pathological diagnosis and the treatment planning of surgical procedures. This study was undertaken to develop a new technique for simulating anatomical structures and to clarify the morphological and clinical characteristics of the maxillary sinus. Thirty-three hemi-sectioned Korean heads were used in this study. CT scans and DentaScan reformatted cross-sectional images were taken on all specimens. From the CT images, three-dimensional reconstructed images were made using the V-works program. From the three-dimensional reconstructed images of the maxillary sinus, six categories of maxillary sinus were created, categorized according to their lateral aspects and shapes of the inferior walls. In 55%, a flat inferior wall of the maxillary sinus was observed. All measurements (anterior-posterior length, height, width and volume) of the sinus were larger in males than in females. From the DentaScan reformatted panoramic images, the anterior limit of the maxillary sinus was located in the first premolar area (58%), and the posterior limit was in the third molar and maxillary tuberosity area (94%). We therefore offer a new virtual technique for manipulating three-dimensional reconstructed images easily on a personal computer. On the reconstructed images the three-dimensional morphology could be observed and the anatomical characteristics of the maxillary sinus and surrounding structures could be determined.