BACKGROUNDpAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.METHODSThe expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.RESULTSExpression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.CONCLUSIONSPatients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.
Abstract Transmembrane 4 super family member 4(TM4SF4) protein has been shown to be involved in EMT-associated stemness through autocrine of insulin-like growth factor 1(IGF1) and osteopontin(OPN) in non-small cell lung cancer(NSCLC) cells. However, its potential as a therapeutic target has not been evaluated. In this study, anti-human TM4SF4 monoclonal antibodies(anti-hTM4SF4 mAbs) were prepared in mouse as part of a strategy for developing anticancer drug using humanized antibody. A synthetic peptide(15 mer, 126-140th AA) derived from the extracellular loop(ECL) 2 of human TM4SF4 exposed on outer cell surface was used as an immunization antigen. Among the selected anti-hTM4SF4 mAbs, ECL-2B7 and ECL-12A8 showed the best affinity for the antigen(Kd), approximately 2.66 nM and 8.34 nM, as determined by surface plasmon resonance analysis. Using mouse xenograft of NSCLC cell line, it was confirmed that ECL-2B7 was superior to ECL-12A8 in producing humanized antibody. ECL-2B7 inhibited EMT-associated stemness of TM4SF4 positive cancer cells by blocking cellular signaling events such as IGF1Rβ and CD44 and their downstream signals, PI3K/AKT/GSK3β/NF-κB and JAK2/STAT3 pathways. ECL-2B7 also enhanced antitumor activity by downregulating cellular and exosomal level of PD-L1 and B7-H4, immune-checkpoint ligands that elicit immunosuppression of T cell, and by mediating antibody-dependent cellular cytotoxicity. Treatment with OPN- and IGF1-neutralizing antibodies suppressed intracellular PD-L1 and B7-H4 level. It means that the regulation of PD-L1 and B7-H4 levels by TM4SF4 is closely related to the autocrine action of OPN and IGF1 induced by TM4SF4. Using patient-derived xenograft model, it was confirmed that the ECL-2B7 has excellent antitumor activity that effectively inhibits tumor progress. These results strongly suggest that it is necessary to construct humanized antibody based on ECL-2B7 to confirm its potential as a novel anticancer drug. Citation Format: Rae Kwon Kim, Chang-Kyu Heo, Yeon-jee Kahm, Uhee Jung, Byung-Chul Shin, Won-Yong Kim, Bum-Jin Kim, Sung-Chul Kim, Chun-jeih Ryu, Eun-Wie Cho, In-Gyu Kim. A novel monoclonal antibody targeting TM4SF4 enhances antitumor activity through regulation of cellular levels of immune checkpoint ligands and antibody dependent cellular cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3189.
The present paper deals with characteristics of resistance performance according to the variation of synthetic ice thickness and hull form. The resistance test has been conducted with pack ice condition in Pusan National University towing tank. Stem angle has been chosen as main parameters for the variation of hull form characteristics, which is the most important factor especially in icebreaking cargo vessel. The serial comparisons of resistance test have been done with the variation of hull form parameter as well as with the different thickness of synthetic ice. The different trend of resistance performances with increasing of stem angle has been shown at each synthetic ice thickness. The present test results is expected to be confirmed by comparing the test results in ice tank in the near future.
Tc-Labeled N-(3-bromo-2,4,6-trimethylacetanilido)-iminodiacetic acid (Tc-mebrofenin) has been used to assess the functional integrity of the hepatobiliary system. A fast and convenient procedure was established for the synthesis of mebrofenin and radiochemical labeling with Tc. 3-Bromo-2,4,6-trimethylacetanilide was synthesized in large scale under microwave irradiation (300 W, 5 min) by acylation (60% yield) and bromination (96% yield). And it was treated with the disodium salt of iminodiacetic acid under microwave irradiation (300 W, 20 min) to afford mebrofenin in 86% yield. The attractive feature in this procedure involves microwave irradiation that results in shorter reaction times, higher yields, cleaner reaction products and an easier work-up than classical heating. The synthesis time of 2,4,6trimethylacetanilide was reduced from 1 h to 5 min; the synthesis time of 3-bromo-2,4,6-trimethylacetanilide was reduced from 24 h to 5 min; the synthesis time of mebrofenin was reduced from 48 h to 20 min, when compared with that of the conventional method. Iminodiacetic acid of mebrofenin is a metal complexing moiety that strongly binds Tc. Tc-Mebrofenin between the reduced technetium, prepared by a stannous reduction of the pertechnetate ion, and mebrofenin was formed under microwave irradiation (300 W, 1 min). The synthesis time of Tc-mebrofenin was reduced from 30 min to 1 min, when compared with that of the conventional method. 99.5% of Labeling efficiency (LE) of Tc-mebrofenin was determined by using radio-TLC.
Heart rate variability was compared in 20 subjects taking traditional herbal remedy (Ondamtanggamibang) or placebo control pill, in placebo controlled design experiment. Herbal remedy group reported more pleasant and clam emotions than did the placebo group. Herbal remedy reduced the heart rate and increased heart rate variability (HRV) as indicated by a reduced low frequency/high frequency power ratio of heart rate variability. With nonlinear analysis, the Poincaré plot index of HRV and approximate entropy was greater in the herbal remedy group than in the control group. These findings suggest that herbal remedy stabilizes the sympathovagal function and cardiac autonomic nervous system by inducing more positive emotions than does placebo therapy. In conclusion, herbal remedy may act by stabilizing both the autonomic nervous system and the emotional state.
우리나라 약사법과 외국의 방사성의약품 제조관리기준 가이드라인을 참고하여 방사성의약품 제조관리기준 제정 시 고려해야할 사항들에 대해 의견을 제시하였다. 의약품은 안전성, 유효성과 더불어 제품의 균일성이 검증되어야 한다. 따라서 방사성의약품의 특성을 충분히 고려한 합리적인 제조관리기준을 제정하면 방사성의약품 관리의 효율성을 증대시키고 국민건강 증진에 기여할 수 있을 것으로 기대된다. This study suggests considerations for legislation of radiopharmaceutical manufacturing practice according as the Korea Pharmaceutical Affairs Act and guidelines on foreign radiopharmaceutical manufacturing practice. Pharmaceuticals should be verified safety, effectiveness, and uniformity. Therefore, it is expected that the efficiency of the administration of radiopharmaceuticals increase and nation's health promote if rational manufacturing management to consider of radiopharmaceutical properties is legislated.
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