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Background: The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients and methods: Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/ m²) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Results: Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. Conclusion: In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. [ABSTRACT FROM AUTHOR]

Background: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA., Patients and Methods: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR)., Results: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA., Conclusions: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches., Competing Interests: Disclosure DVTC has received personal fees from Archer, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Five Prime Therapeutics, Foundation Medicine, Guardant Health, Tempus Labs, Genentech/Roche, Gritstone Oncology, Lilly, Merck, Novartis, AstraZeneca, Natera, Pieris Pharmaceuticals, QED Therapeutics, Seattle Genetics, Taiho Pharmaceutical, and Zymeworks. YKK has received consulting fees from ALX Oncology, Amgen, Blueprint Medicines, Bristol Myers Squibb, Daehwa Pharmaceutical, MacroGenics, Merck & Co., Inc., Novartis, Roche, Surface Oncology, and Zymeworks. HHY has received payments to the institution for grants from Bristol Myers Squibb and Merck & Co., Inc.; consulting fees from ALX Oncology, Astellas Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, MacroGenics, Merck & Co, Inc., Novartis, OncXerna Therapeutics, and Zymeworks; honoraria from BeiGene; and advisory board or data safety monitoring board payments from ALX Oncology, Astellas Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, MacroGenics, Merck & Co., Inc., Novartis, OncXerna Therapeutics, and Zymeworks. DYO has received grants from Array BioPharma, AstraZeneca, BeiGene, Lilly, HANDOK, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Novartis, and Servier Pharmaceuticals; and participated in advisory boards for ASLAN Pharmaceuticals, AstraZeneca, Basilea Pharmaceutica, Bayer, BeiGene, Celgene, a Bristol-Myers Squibb Company, Genentech/Roche, Halozyme, Merck Serono, Novartis, Taiho Pharmaceutical, Turning Point Therapeutics, and Zymeworks. AIS has received stock payments from Lilly; payments for leadership role from NEXT Oncology; honoraria from Amgen, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, CytomX Therapeutics, Janssen Oncology, Merck, Novartis, and Takeda; and personal and institutional payments for advisory boards from Amgen, Array BioPharma, AstraZeneca, Bristol Myers Squibb, Gritstone Oncology, Incyte, Janssen Research and Development, Merck & Co., Inc., Mirati Therapeutics, Novartis, and Takeda; consulting fees from Amgen, Array BioPharma, AstraZeneca, Bristol Myers Squibb, Gritstone Oncology, Janssen Research and Development, Jazz Pharmaceuticals, Incyte, Merck & Co., Inc., Mirati Therapeutics, Novartis, and Takeda; and grants and other support from AbbVie, ADC Therapeutics, Amgen, Arch Therapeutics, Astellas Pharma, Astex Pharmaceuticals, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Gritstone Oncology, Ignyta, Incyte, Janssen Oncology, LAM Therapeutics, Loxo Oncology, MacroGenics, MedImmune, Mirati Therapeutics, NewLink Genetics, Novartis, Plexxikon, Roche, Rubius Therapeutics, Takeda, and TrovaGene. SVU has participated in advisory boards for Array BioPharma, Bayer, Eisai, Exelixis, Incyte, and Syros Pharmaceuticals; and grants to institution from AbbVie, ArQule, AstraZeneca, Atreca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, a Bristol-Myers Squibb Company, CicloMed, Evelo Biosciences, Exelixis, G1 Therapeutics, GlaxoSmithKline, IGM Biosciences, Incyte, Isofol Medical, KLUS Pharma, MacroGenics, Merck & Co., Inc., Mersana Therapeutics, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Revolution Medicines, Synermore Biologics, Takeda, Tarveda Therapeutics, Tesaro, Tempest Therapeutics, and Vigeo Therapeutics. EJA has received research funding from Bristol Myers Squibb, AstraZeneca, Seagen, AbbVie, and Lilly; consulting fees from AstraZeneca, Janssen Biotech, and McKesson. PMB has received consulting fees from Bristol Myers Squibb and Merck; grants/research support to institution from Ipsen, Processa Pharmaceuticals, AbbVie, MacroGenics, Merck, Taiho Pharmaceutical, and Athenex. JC has received consulting fees from Amgen, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Foundation Medicine, Lilly, MacroGenics, Merck & Co., Inc., Novartis, Ono Pharmaceutical, Silverback Therapeutics, and Turning Point Therapeutics; speaker’s bureau honorarium from Bristol Myers Squibb and Merck and Co., Inc.; data safety monitoring board member fees from Yiviva; and research payments to the institution from Brooklyn ImmunoTherapeutics, MacroGenics, and Merck & Co., Inc. HCC received grants/research support from Lilly, GlaxoSmithKline, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Merck Serono, Bristol Myers Squibb/Ono Pharmaceutical, Taiho Pharmaceutical, Amgen, BeiGene, Incyte, and Zymeworks; received honoraria from Lilly and Merck Serono; and did consultation for Amgen, BeiGene, Bristol Myers Squibb, Celltrion, Gloria Therapeutics, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Merck Serono, Taiho Pharmaceutical, and Zymeworks. FG has received consulting fees for participating on advisory boards from Janssen, Epizyme, and Regeneron/Sanofi; speaker’s bureau honorarium from Epizyme, Regeneron/Sanofi, and Pfizer. SJK has received consulting fees for participating on advisory boards from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Lilly, Merck & Co., Inc., Natera, and Pieris Pharmaceuticals; and stock options from Turning Point Therapeutics. KWL has received consulting fees from Bayer, Bristol Myers Squibb, Daiichi Sankyo, and ISU ABXIS; honorarium from Boryung Pharmaceutical and Ono Pharmaceutical; and research grants to the institution from ABL Bio, ALX Oncology, Astellas Pharma, AstraZeneca, BeiGene, Bolt Biotherapeutics, Daiichi Sankyo, Five Prime Therapeutics, Genexine, Green Cross Corp, InventisBio, Leap Therapeutics, LSK BioPharma, MacroGenics, MedPacto, Merck KGaA, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Oncologie, Pharmacyclics, Ono Pharmaceutical, Pfizer, Seagen, Taiho Pharmaceutical, Trishula Therapeutics, Y-Biologics, and Zymeworks for conducting clinical trials. JP has received honoraria from Agendia, Guardant Health, and Tempus; consulting fees from TerSera Therapeutics; research funding for clinical trials from AbbVie, BerGenBio, Calithera Biosciences, Inc, eFFECTOR Therapeutics, EMD Serono, Epizyme, Genentech/Roche, Immunity Bio, Immutep S.A.S., Incyte, Janssen Pharmaceuticals, Jounce Therapeutics, Lilly, KeChow Pharma, Loxo Oncology, MacroGenics, Inc., Merck, Mirati, Natera, Novocure Ltd, Sermonix Pharmaceuticals, TerSera Therapeutics, Turning Point Therapeutics, Salarius Pharmaceuticals, Immunomedics, Pfizer, and Kyowa Kirin; and owns stocks of Oncology Consultants, Zogen, Spectrum Pharmaceuticals, Roche, TerSera Therapeutics. LS has received consulting fees from Boehringer Ingelheim, Haichuang Pharmaceutical, Harbour BioMed, Merck & Co., Inc., Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., and Mingji Biopharmaceutical; speaker’s bureau fees from CStone Pharmaceuticals, Jiangsu Hengrui Pharmaceuticals, Hutchison Whampoa, and Zai Lab; participated on advisory boards for Bristol Myers Squibb, CStone Pharmaceuticals, Rongchang Pharmaceuticals, and Zai Lab; and grants to the institution from Beihai Kangcheng (Beijing) Medical Technology, Beijing Xiantong Biomedical Technology, Jacobio Pharmaceuticals, Qilu Pharmaceutical, and Zai Lab. MM has received grants and nonfinancial support from the AIO, BMBF, EORTC, and German Cancer Aid; personal fees from Amgen, Bristol Myers Squibb, Falk Foundation, Lilly, MGI Group, Merck Serono, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Pfizer, Roche, and Taiho Pharmaceutical; grants to the institution from Amgen, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., and Pfizer; and nonfinancial support from Amgen and Bristol Myers Squibb paid to the institution. JS, DL, and MKR are/were employees of MacroGenics and hold stock in the company. HP has received grants to institution from Adlai Nortye USA, Alpine Immune Sciences, Ambrx, Amgen, Aprea Therapeutics AB, Array BioPharma, Bayer, BeiGene, BJ Bioscience Inc., Bristol Myers Squibb, Daiichi Sankyo, Lilly, Elicio Therapeutics, EMD Serono, Exelixis, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Hoffman-La Roche, Hutchison MediPharma, ImmuneOncia Therapeutics, Incyte, Jounce Therapeutics, MabSpace Biosciences, MacroGenics, MedImmune, Medivation, Merck & Co., Inc., Millennium Pharmaceuticals, Mirati Therapeutics, Novartis, Oncologie, Pfizer, PsiOxus Therapeutics, Puma Biotechnology, Regeneron Pharmaceuticals, Repare Therapeutics, Seattle Genetics, Synermore Biologics, Taiho Pharmaceutical, TopAlliance Biosciences, Turning Point Therapeutics, Vedanta Biosciences, and Xencor; writing support from MacroGenics; and participated in advisory boards for Jacobio Pharmaceuticals. BYS, STK, SCO, and MBS have declared no conflicts of interest. Data sharing The data collected for the study will not be made available to others., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The RAINBOW trial showed that second-line ramucirumab with paclitaxel prolongs overall survival (OS) and progression-free survival (PFS) compared with placebo plus paclitaxel for treatment of advanced gastric/gastroesophageal junction cancer. Plasma samples were collected from patients during the trial and tested to identify predictive and prognostic biomarkers., Patients and Methods: Circulating factors in plasma samples from mutually exclusive subsets of RAINBOW patients were assayed using: Intertek assays (24 markers, 380 samples, 57% of patients) and Lilly-developed assay (LDA) platform (5 markers, 257 samples, 39% of patients). Time-trend plots were generated for each marker from the Intertek assays. Baseline patient data were dichotomized into low- and high-marker subgroups. Markers were analyzed for predictive effects using interaction models and for prognostic effects using main-effects models., Results: The Intertek and LDA populations were representative of the full trial population. Plasma levels of VEGF-D and PlGF increased from baseline levels during treatment, then declined after treatment discontinued. Angiopoietin-2 exhibited a decrease during treatment, then increased after treatment discontinuation. No clear time trend was evident with the other markers. Analyses of baseline biomarker expression and its relationship with efficacy variables found no biomarker was predictive for efficacy outcomes, including VEGF-D. However, CRP, HGF, ICAM-3, IL-8, SAA, and VCAM-1 were identified as potential prognostic markers with low baseline levels corresponding to longer OS and PFS., Conclusions: Pharmacodynamic and prognostic relationships were found from the exploratory biomarker analyses in RAINBOW; however, no predictive markers for ramucirumab in gastric cancer were identified in this trial., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients., Methods: From urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m 2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group., Results: Fifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283-4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947-479.578; P = .054)., Conclusions: A uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30-59 mL/min/1.73 m 2 ) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure., Methods and Materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25., Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%)., Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC., Clinicaltrials.gov: NCT01839773.

We generated new fusion genes carrying positive- and negative-selection markers, and a reporter gene in a single reading frame. The new genes were constructed by sequentially linking the coding sequences of drug-resistance genes (hygro, or puro), a green fluorescence protein (GFP) gene (gfp), and the thymidine kinase gene (tk). The new synthetic genes (hygro/gfp/tk and puro/ gfp/tk) were inserted into retroviral vectors to test their usefulness as selective markers and reporters. The genes were functional in a positive selection in the presence of hygromycin (hygro/gfp/tk) or puromycin (puro/gfp/ tk). In addition, cells expressing the new fusion genes were clearly identifiable by their green fluorescence emitted from GFP. At the same time, these cells were sensitive to a gancyclovir treatment, allowing efficient removal of the transduced cells. The presently described synthetic genes will be valuable tools in both gene therapy and basic gene transfer studies, where positive selection of the transduced cells, monitoring gene expression, and negative selection of the transduced cells are simultaneously required.

PRK1, a receptor-like kinase that is expressed in pollen, pollen tubes, and ovaries, has been shown to play important roles in pollen development and embryo sac development in Petunia inflata. We have used the kinase domain of PRK1 as a bait in the yeast two-hybrid system to identify PRK1-interacting proteins. The screening resulted in isolation of a cDNA encoding a protein highly homologous to the human and yeast beta-subunit of translation initiation factor 2B (eIF2B-beta), which was designated NeIF2Bbeta. eIF2B is a guanine nucleotide exchange protein that functions in the regulation of translation in eukaryotic cells. Deletion mutants of NeIF2Bbeta were analyzed for their interaction with PRK1, and the results suggested that the N-terminal half of NeIF2Bbeta, especially the region between residue 103 and 235, is important for the interaction. This protein association was confirmed by in vitro binding assay of the recombinant NeIF2Bbeta and PRK1 proteins. Despite high sequence homology between NeIF2Bbeta and its yeast counterpart, the NeIF2Bbeta cDNA could not rescue the phenotype of the yeast mutant strain lacking the GCD7 gene encoding eIF2B-beta, when transferred into the mutant strain.

Purpose: This investigation was designed to determine whether heat pressing and/or simulated heat treatments affect the flexure strength and microstructure of the lithium disilicate glass-ceramic of the IPS Empress 2 system., Materials and Methods: Four groups of the lithium disilicate glass-ceramic were prepared as follows: group 1 = as-received material; group 2 = heat-pressed material; group 3 = heat-pressed and stimulated initial heat-treated material; and group 4 = heat-pressed and simulated heat-treated material with full firings for a final restoration. Three-point bending tests and scanning electron microscopy (SEM) analysis were conducted., Results: The flexure strength of group 2 was significantly higher than that of group 1. However, there were no significant differences in strength among groups 2, 3, and 4, or between groups 1 and 4. The SEM micrographs of the lithium disilicate glass-ceramic showed a closely packed, multidirectionally interlocking microstructure of numerous lithium disilicate crystals protruding from the glass matrix. The crystals in the glass matrix of the heat-pressed materials (groups 2, 3, and 4) were a little more homogeneous and about 2 times bigger than those of the as-received material (group 1). These changes of the microstructure were greatest between groups 1 and 2. However, there were no marked differences among groups 2, 3, and 4., Conclusion: Although there were significant increases in the strength and some changes of the microstructure after the heat-pressing operation, the combination of heat pressing and simulated subsequent heat treatments did not produce an increase of strength of IPS Empress 2 glass-ceramic.

The idea of combining the network of HMMs and the dynamic programming-based search is highly relevant to online handwriting recognition. The word model of HMM network can be systematically constructed by concatenating letter and ligature HMM's while sharing common ones. Character recognition in such a network can be defined as the task of best aligning a given input sequence to the best path in the network. One distinguishing feature of the approach is that letter segmentation is obtained simultaneously with recognition but no extra computation is required.

Purpose: This article reviews recent research on the esthetics of the smile, covering the attractiveness of the smile, the effect of aging on the smile, oral condition and the smile, personality and smile, and smile exercises., Material and Methods: The subjects were Koreans with normal occlusion. Photographs of a full smile were taken and the esthetic quality of the subjects' smiles was estimated. Smile scores were correlated with oral condition, personality, the practice of smile exercises, and elements of the smile, such as the position of the lip in a smile. The personality of the subjects was assessed by means of a Sixteen Personality Factor Questionnaire. Gibson's smile exercises were used to investigate the effect of smile exercise., Results: In an attractive smile, the full shape of the maxillary anterior teeth was shown between the upper and lower lip, the upper lip curved upward or was straight, the maxillary anterior incisal curve was parallel to the lower lip, and teeth were displayed to the first molar. The amount of maxillary incisal exposure gradually decreased with age, accompanied by a gradual increase in mandibular incisal exposure. Personality traits such as warmth, calmness, extroversion, and low anxiety were closely related to an attractive smile. Smile exercises were an effective means of improving the esthetic level of the smile if patients exercised continuously., Conclusion: An attractive smile is important for esthetic treatment. The lip position, oral condition, personality traits, and smile exercise affect the esthetics of the smile.

The effect of intravesical Bacillus Calmette-Guérin (BCG) on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced urinary bladder carcinogenesis was pathologically evaluated. As a suppressive study of BCG on initiation, F344 female rats given 0.05% BBN orally for 6 weeks had intravesical instillation of either BCG or saline 3 times during BBN administration (Group A). As an inhibitory study of BCG on promotion, F344 female rats given the same strength BBN for 10 weeks had intravesical instillation of either BCG or saline 4 times starting at 7th week of BBN administration (Group B). The bladders were extirpated at 18th or 36th week after BBN administration in Group A and at 10th or 18th week in Group B. The lesions in the bladder were classified into 4 pathological findings; simple hyperplasia, papillary or nodular hyperplasia, papilloma and transitional cell carcinoma. The incidence of the lesions and the number of the lesions per 10 cm basement membrane were observed. BCG did not inhibit the growth of transitional cell carcinoma in Group A nor in Group B, rather partly promoted carcinogenesis. These results indicate that BCG have no inhibitory effect on carcinogenesis. We concluded that prophylactic effect of intravesical BCG is not due to inhibition of carcinogenesis but elimination of residual tumors by strong antitumor effect of BCG.

Fifty-two patients with ulcerative colitis and colorectal cancer undergoing colectomy at the Mount Sinai Hospital between 1973 and 1988 were studied retrospectively to determine the correlation of age, sex, duration of colitis, tumor location, number of cancers, tumor differentiation, colloid content, presence of signet ring cells, Dukes' classification, and DNA ploidy with survival. The mean age was 45 years, with a mean duration of colitis of 21 years. Five patients (10%) had Dukes' A lesions, 17 (33%) had Dukes' B lesions, 17 (33%) had Dukes' C lesions, and 13 (25%) had distant metastases. Thirty patients (58%) had well- or moderately differentiated tumors, whereas tumors were poorly differentiated in 22 (42%). Twenty-eight patients (54%) had colloid tumors, and, in 14 (27%), signet ring cells were present. Thirty-one patients (60%) had nondiploid tumors. Actuarial analysis revealed that the 5-year survival rate was significantly worse for patients with nondiploid tumors (76% versus 32%). When stratified by stage, only patients with Dukes' C lesions showed a significant difference in survival for diploid versus nondiploid tumors. Multivariate analysis showed that the Dukes' classification was the best prognostic indicator, followed by tumor differentiation and DNA ploidy. Tumor location, colloid content, number of cancers, duration of disease, age, and sex did not correlate with the prognosis.

Existing approaches to routing hazardous material shipments by rail recognize that track condition is an important influence, but have not included it in the risk assessment and routing models. This note explores the influence of track condition based on predictions of internal defects in the rail. The method developed predicts the expected frequency of accidents and subsequent consequences in terms of the expected number of fatalities accounting for one aspect of track condition-internal defects. It is intended to indicate the magnitude and impact of track condition. The formulation integrates models of consequences and the risk of a hazardous spill found in the literature with the frequency of accidents as a function of the number of defects. The number of defects may be based on observations or predicted as a function of the cumulative traffic. The models are used to calculate the expected number of fatalities per year for a particular route. Application of the methodology to a hypothetical route shows that the risk associated with the transportation of hazardous material shipments varies significantly with the expected number of defects in the track. Therefore, risk not only varies from route to route but over time for any section of track as the condition deteriorates.

Several studies have shown that the presence of DNA ploidy abnormalities, measured by flow cytometry, may correlate with a poor prognosis in a variety of cancers. The predictive value of these DNA abnormalities in young patients with colorectal cancer has not been well studied. Fifty patients aged 40 years and younger with colorectal adenocarcinoma were studied to determine the correlation of tumor DNA abnormalities with survival. DNA content was determined by flow cytometric analysis and each tumor was categorized as diploid or nondiploid. Of the parameters studied, Dukes' classification and tumor DNA ploidy were found to be significant prognostic indicators. Determination of DNA content seems to provide additional useful prognostic information in young patients with colorectal cancer.