• Title/Summary/Keyword: bombesin

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Dendritic-like Cells Accumulate in BPD Lung of Baboon (만성 폐질환인 폐이형성증을 보이는 baboon 폐조직에 Dendritic-like cell의 축적)

  • Lee, Jong-Hwan;Kim, Kwang-Hyeon
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1202-1206
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    • 2008
  • The present investigation demonstrates HLA-DR and PGP9.5 double positive cells accumulate thymus cortical region in normal baboon thymus and baboon lung. But, these cells disappeared in thymus and lung of bronchopulmonary dysplasia (BPD) animals. 125d GC animal model is more suitable for BPD than 140d GC animal. Anti-bombesin antibody, 2A11 treated baboon recover normal level of HLA-DR positive cells from BPD animal. In addition, thymocytes show responsiveness for bombesin. These observation suggest that blocking BLPs protects a chronic lung injury by BPD and 2A11 is possible agent for passive therapy of BPD.

Development of bombesin peptide kit for prostate cancer diagnosis and treatment using 64Cu/177Lu.

  • Kim, Mi Hyun;Kim, Min Hwan;Kim, Kwang Il;Kim, Jung Young;Lee, Tae Sup;Kang, Joo Hyun;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.59-64
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    • 2017
  • It has been reported that $^{64}Cu$ was radiolabeled with bombesin (BBN) peptide binding to the gastrin releasing peptide receptor expressed in human prostate cancer cells (PC3), confirming tumor target efficacy in mouse model. In this study, we developed the kit for the diagnosis and treatment of prostate cancer that can be used clinically using bombesin peptide available of $^{64}Cu$ and $^{177}Lu$ radioisotope labeling. The NODAGA-galacto-BBN peptide containing the NODAGA chelator and galactose was dispensed into a sterilized glass vial and lyophilized to prepare a kit. The stability of the kit after long-term storage in the $4^{\circ}C$ cold chamber and the radiolabeling efficiency after $^{64}Cu$ or $^{177}Lu$ labeling were confirmed by thin layer chromatography. When labeling with $^{64}Cu$ at the initial stage of storage, labeling efficiency of NODAGA-galacto-BBN peptide kit was over 96%, labeling efficiency was over 90% when $^{177}Lu$ was labeled. At 11 months after storage, the radiolabeling efficiency of kit against $^{64}Cu$ and $^{177}Lu$ was each over 95% and 90%. The cell viability was significantly reduced in the $^{177}Lu$-NODAGA-galacto-BBN treated group compared with the control and $^{177}Lu$ alone treated group in clonogenic assay. In conclusion, the NODAGA-galacto-BBN kit prepared by the lyophilization showed high stability over time and high yield of radioisotope labeling. Also $^{177}Lu$-NODAGA-galacto-BBN confirmed high cytotoxicity to prostate cancer cells. Therefore, the NODAGA-galacto-bombesin kit is expected to be useful for the diagnosis and treatment of prostate cancer patients.

Novel Bombesin Analogues Conjugated with DOTA-Ala(SO3H)-4 aminobenzoic acid and DOTA-Lys(glucose)-4 aminobenzoic acid: Synthesis, Radiolabeling, and Gastrin Releasing Peptide Receptor Binding Affinity

  • Lim, Jae Cheong;Choi, Sang Mu;Cho, Eun Ha;Kim, Jin Joo
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.191-200
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    • 2013
  • In this study, a novel bombesin (BBN) analogues, DOTA-Ala($SO_3H$)-4 aminobenzoyl-Gln-Trp-Ala-Val-Gly-His-Leu-Met-$NH_2$ (DOTA-sBBN) and DOTA-Lys(glucose)-4 aminobenzoyl-Gln-Trp-Ala-Val-Gly-His-Leu-Met-$NH_2$ (DOTA-gluBBN), were synthesized and radiolabeled, and their binding affinities were evaluated. Peptides were prepared by a solid phase synthesis method and their purities were over 98%. DOTA is the chelating agent for $^{177}Lu$-labeling, and the DOTA-conjugated peptides were radiolabeled with $^{177}Lu$ by a high radiolabeling yield (>98%). The Log P values of DOTA-sBBN and DOTA-gluBBN were -2.20 and -2.79, respectively. 50.41% of $^{177}Lu$-DOTA-sBBN and 72.97% of $^{177}Lu$-DOTA-gluBBN were left undegraded by the serum incubation at $37^{\circ}C$ for 48 hr. A competitive displacement of $^{125}I-[Tyr^4]$-BBN on the PC-3 human prostate carcinoma cells revealed that 50% inhibitory concentration ($IC_{50}$) were 1.46 nM of DOTA-sBBN and 4.67 nM of DOTA-gluBBN indicating a highly nanomolar binding affinity for GRPR. Therefore, it is concluded that $^{177}Lu$-DOTA-sBBN and $^{177}Lu$-DOTA-gluBBN can be potential candidates as a targeting modality for the Gastrin-releasing peptide receptor (GRPR)-over-expressing tumors, and further studies to evaluate their biological and pharmacological characteristics are needed.

Immunohistochemistry of Endocrine Cells in the Alimentary Tract of the Tree Frog, Hyla arborea japonica

  • Ku, Sae-Kwang;Lee, Hyeung-Sik;Lee, Jae-Hyun
    • Animal cells and systems
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    • v.4 no.1
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    • pp.95-100
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    • 2000
  • The regional distribution and relative frequencies of endocrine cells were studied immunogistochemically (PAP methods) in the alimentary tract of the tree frog, Hyla areorea japonica, using specific antisera against serotonin, somatostatin, bovine Sp-1/chromogranin (BCG), cholecystokinin (CCK)-8, vasoactive intestinal polypeptide (VIP), gastrin, bombesin, secretin and pancreatic polypeptide (PP). Six kinds of endocrine cells were identified in this study, These immunoreactive cells were located in the gastric glands of stomach regions and in the basal portion of the epithelium of the intestinal tract or esophagus with variable frequencies. They were spherical or spindle-shaped. Serotonin-immunoreactive cells were observed in the whole alimentary tract including the esophagus. Somatostatin-immunoreactive cells were also detected throughout the alimentary tract except the rectum. CCK-8-immunoreactive cells were observed from the pylorus to ileum. Vip-immunoreactive cells were restricted to the rectum. Bombesin-immunoreactive cells were restricted to the fundic gastric regions and gastrin-immunoreactive cells were restricted to the pylorus. However, no BCG-, secretin and PP-immunoreactive cells were demonstrated in this study. In conclusion, the regional distribution and relative frequency of the endocrine cells in the alimentary tract of the tree frog were similar to other anuran species, but some differences which may be caused by feeding habits and species specification were also observed.

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Isolation of Bombesin-Like Substances from the Skin of the Frog, Bombina orientalis: Its Molecular Heterogeneity and Biological Activity (한국에 서식하는 무당개구리의 피부에서 추출된 Bombesin 유사물질의 분자적 이질성 및 생물학적 활성)

  • Park, Hyoung-Jin;Lee, Yun-Lyul;Kwon, Hyeok-Yil;Shin, Won-Im;Suh, Sang-Won
    • The Korean Journal of Physiology
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    • v.23 no.1
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    • pp.79-87
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    • 1989
  • Molecular property as well as biological activities of bombesin-like substance (BBS-LS) isolated from the skin of B. orientalis in Korea was compared with those of synthetic BBS-14. BBS-LS in the crude extract was applied on a Sephadex G-50, superfine column $(1.6{\times}112\;cm)$. On chromatogram, the first peak (3.5% of BBS-LS) was found ahead of synthetic GRP-27, and the second peak (rest) between synthetic GRP-27 and synthetic BBS-14. The main form of BBS-LS was successfully purified by using a column of alkaline alumina followed by sequential gel-filtrations on a column of Sephadex G-10, fine and a column of Sephadex G-50, superfine. Chromatographic analysis of the purified BBS-LS using a column of Sephadex G-50, superfine and reversed phase HPLC revealed that the main form of BBS-LS in the skin of B. orientalis could be distinctly different from either BBS-14 or GRP-27 in molecular size. The purified BBS-LS exerted biological activities quite identical to those of synthetic BBS-14. The results of the present investigation indicate that the skin of B. orientalis contains BBS-LS composed of two distinct forms. The main form of BBS-LS purified in the present study is heterogenous to both synthetic BBS-14 and GRP-27 in molecular size but identical to BBS in biological activities.

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An immunohistochemical study of endocrine cells in the alimentary tract and pancreas of the toad, Bufo bufo gargarizans Cantor (두꺼비(Bufo bufo gargarizans cantor)에서 위장췌내분비세포의 면역조직화학적 연구)

  • Lee, Hyeung-sik;Ku, Sae-kwang;Park, Ki-dae;Lee, Jae-hyun
    • Korean Journal of Veterinary Research
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    • v.40 no.1
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    • pp.17-26
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    • 2000
  • The regional distribution and relative frequencies of endocrine cells were studied immunohistochemically (PAP methods) in the alimentary tract and pancreas of the toad, Bufo bufo gargarizans Cantor using specific antisera against bovine Sp-1/chromogranin (BCG), serotonin, bombesin, gastrin, substance P (SP), somatostatin, insulin, glucagon, pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP) and secretin. Nine kinds of endocrine cells were identified in this study. Spherical or spindleshaped immunoreactive (IR) cells were located in the gastric glands of stomach regions, in the basal portion of the epithelium of intestinal tract or esophagus, and in the exocrine or pancreatic islets with variable frequencies. In the alimentary tract, BCG-IR cells were found in the fundus and pylorus with rare and a few frequencies, respectively. Serotonin-IR cells were demonstrated in the whole alimentary tract including the esophagus. Bombesin- and SP-IR cells were restricted to the stomach regions and gastrin-IR cells were restricted to the pylorus. Somatostatin-IR cells were detected throughout the whole alimentary tract except for the large intestine, However, insulin-, glucagon-, PP-, VIP- and secretin-IR cells were not detected in the alimentary tract. In the pancreas of toad, the distribution and relative frequency of endocrine cells were similar to those of other mammals. Insulin-IR cells were located in the central portion of the pancreatic islets and interspaces of exocrine portions, and glucagon-, somatostatin- and PP-IR cells were detected in the marginal regions of the pancreatic islets and interspaces of exocrine. However, other IR cells were not found in the pancreas. In conclusion, the regional distribution and relative frequency of the endocrine cells in the alimentary tract and pancreas of the toad were similar to other anuran species but some differences which might be caused by feeding habits and species specification were also observed.

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Neuromedin B modulates phosphate-induced vascular calcification

  • Park, Hyun-Joo;Kim, Mi-Kyoung;Kim, Yeon;Kim, Hyung Joon;Bae, Soo-Kyung;Bae, Moon-Kyoung
    • BMB Reports
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    • v.54 no.11
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    • pp.569-574
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    • 2021
  • Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification.

An immunohistochemical study of endocrine cells in the gut of the Prussian carp, Carassius auratus (붕어(Carassius auratus) 장 내분비세포에 관한 면역조직화학적 연구)

  • Lee, Hyeung-Sik;Ku, Sae-Kwang;Park, Gi-Dae;Lee, Jae-Hyun
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.477-484
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    • 2001
  • The regional distribution and relative frequency of neurohormonal peptides-producing cells were demonstrated in the gut of the stomachless teleost, the Prussian carp, Carassius auratus Linnaeus, using 10 types of specific antisera raised against mammalian regulatory peptides. The gut of the Prussian carp was divided into five portions from proximal to distal (Segments I~V). Most of immunoreactive cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shape having long cytoplasmic process that reached to the lumen (open typed cell) while cells showing round in shape (close typed cell) were found in the basal portions of epithelial lining occasionally. Somatostatin-, cholecystokinin (CCK)-8- and pancreatic polypeptide (PP)- immunoreactive cells were observed in this study. However, no serotonin-, glucagon-, chromogranin A-, secretin-, vasoactive intestinal peptide (VIP)-, substance P- and bombesin-immunoreactive cells were found. Somatostatin-immunoreactive cells were restricted to most proximal segments of the gut (Segment I) with rare frequency and CCK-8-immunoreactive cells were demonstrated in the proximal segments of the gut (Segments I and II) with a few to rare frequencies. In addition, pancreatic polypeptide-immunoreactive cells were demonstrated in the proximal to middle segments (Segments I~III) with moderated to rare frequencies. In conclusion, the distribution and relative frequency of these immunoreactive cells are well corresponded to the previous reports in stomachless teleost but somewhat peculiar patterns are also detected.

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Immunocytochemical Study on the Enteroendocrine Cells in the Gastrointestinal Tracts of the Korean Snakes (한국산 뱀목 위장관 점막이 장내분비세포에 대한 면역세포화학적 연구)

  • 진원주;조운복;최월봉
    • The Korean Journal of Zoology
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    • v.33 no.3
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    • pp.276-296
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    • 1990
  • This study attempts to investigate several enteroendocrine cells in the gastrointestinal epithelia of the Korean snakes (Dinodon rufozonatum rufozonotum Rhabdophis tigrina tigrina, Enhydris rufodorsata, Agkistrodon blomhoffii brevicaudus, Agkistrodon saxatilis, Agkistodon calginosus). For a light-microscopical examination of immunocytochemistry, the paraffin sections (5 $\mu$ m) of tissue specimens taken from the various parts of the gastrointestinal tract were stained immunocytochemically by PAP procedure with 10 antisera. The frequency of enteroendocrine cells per unit area (mm$^2$) of each mucosa were counted and the shapes of the cells were observed. In Dinodon rufozonatum rufozonatum, Rhobdophis tigrina tigrina, Enhydris rufodorsata, Agkistrodon saxatilis and Agkistrodon caliginosus, cholecystokinin (CCK)-8, gastrin, pancreatic polypeptide (PP) and serotonin cells were observed. But the freuqency of these immunoreactive cells differ trom each portion of gastrointestinal tracts of all species, respectively. In Agkistrodon blomhoffii brevicaudus, CCK-8, gastrin and serotonin cells were observed. CCK-8 and serotonin cells were found in whole gastrointestinal tracts and gastrin cells were observed in pylorus and mucosa of small intestine. The frequency of these cells was different from each portion. The shapes of CCK-8, gastrin, PP and serotonin cells were pyramidal or oval and closed type in stomach. A large number of these cells were spindle in shape and open type in small intestine and anterior pant of large intestine, whereas some cells were closed type. In posterior part of large intestine and rectum, these cells were oval in shape and closed type.

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Distribution, Content and Molecular Heterogeneity of Gastrin-Releasing Peptide in Rat Pancreas

  • Park, Hyung-Seo;Park, Hyoung-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.4
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    • pp.427-432
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    • 1999
  • Although importance of intrapancreatic neurons containing gastrin-releasing peptide (GRP) in control of exocrine secretion has been raised, the nature of GRP in the pancreas is unclear. Thus, the present study was undertaken to see distribution, content and molecular heterogeneity of immunoreactive GRP in the rat pancreas. Content of immunoreactive GRP in the rat pancreas was $2.99\;{\pm}\;0.66$ ng/g wet tissues determined by radioimmunoassay. Immunoreactive GRP was most abundantly expressed in the duodenal part among 3 parts of the pancreas; duodenal, body and splenic part. Vagotomy failed to change the content of immunoreactive GRP in the pancreas. Three distinct forms of immunoreactive GRP, very identical to GRP-27, bombesin-24 and neuromedin C, were observed in the rat pancreas by using reversed phase $C_{18}$ HPLC and Sephadex G-50 superfine column chromatography. Cell bodies of neurons containing immunoreactive GRP were scattered in pancreatic connective tissues and their nerve fibers innervated pancreatic acini and large ducts as determined by immunohistochemistry. The present results suggest that three distinct forms of GRP exist in intrapancreatic GRPergic neurons, which exert a stimulatory role in pancreatic exocrine secretion in rats.

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