• 생명과학회지
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• 제18권9호
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• pp.1202-1206
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• 2008

본 연구에서 정상적인 baboon의 흉선조직 및 폐조직에서 HLA-DR과 PGP9.5항원에 대한 반응성을 나타내는 수지상세포 형태의 세포가 축적되는 것을 보았다. 하지만, 이런 세포들은 baboon 이 BPD즉 폐이형성증에 걸리게 되면 사라진다는 것을 확인하였다. 그리고 140일 제태기간보다 125일 제태 기간을 보낸 미성숙 baboon이 HLA-DR을 가지는 세포가 더 많아 진다는 것을 관찰할 수 있었고 이로 인해 BPD동물모델을 구축하는데 125일 제태 기간을 보낸 동물이 훨씬 적합하다는 것을 알았다. 또한 bombesin의 항체인 2A11을 처리한 baboon (125d-14d/PRN)의 폐조직에서는 정상수준의 HLA-DR positive세포들이 관찰되었다. 더욱이, Baboon의 흉선으로부터 분리한 thymocyte로 bombesin에 대한 chemotaxis를 수행한 결과 세포이동 반응성을 보였다. 이러한 결과들은 생체 내 BLP들을 차단하면 BPD에 의해 야기된 폐이형성증을 막을 수 있고 2A11항체가 수동 면역제로 폐이형성증을 치료할 수 있는 치료제로써의 가능성을 제시하는 것이다.

• 대한방사성의약품학회지
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• 제3권2호
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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.

• 방사선산업학회지
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• 제7권2_3호
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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.

• Animal cells and systems
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• 제4권1호
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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.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.79-87
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• 1989

Bombesin (BBS)은 유럽에 서식하는 무당개구리(Bombina bombina)의 피부로 부터 발견되었으며 이것은 14개의 amino acid로 구성되어 있음이 잘 알려져 있다. 한국에도 유럽의 무당개구리와 종(species)이 다른 무당개구리인 Bombina orientalis가 서식함이 알려졌으나 이 무당개구리의 피부에 BBS가 존재하는 지는 확실치 않다. 그러므로 본 실험에서는 한국에 서식하는 무당개구리의 피부로부터 BBS 유사물질(BBS-LS)을 추출하여 분자적 이질성과 생물학적 활성을 측정하고자 하였다. 박리한 무당개구리 피부를 100% methanol로 처리하여 얻은 추출물의 일부를 Sephadex G-50, superfine column에 부하하고 여기에서 얻은 chromatogram을 분석한 결과 BBS-LS의 3.5%는 합성 gastrin releasing peptide (GRP-27) 보다 앞에 용출되었으며 나머지 96.5%는 GRP-27과 합성 BBS-14의 사이에 용출되었다. alkaline alumina column과 Sephadex G-10, fine column 그리고 Sephadex G-50, superfine column을 연속적으로 이용하여 methanol 추출물로 부터 BBS-LS를 정제 하였다. 정제된 BBS-LS를 Sephadex G-50, superfine column으로 분석한 결과 합성 GRP-27과 합성 BBS-14 사이에 용출되어 BBS-LS가 이미 알려진 BBS-14와 분자의 크기에 있어서 다른 물질임을 알 수 있었다. 정제된 BBS-LS를 reversed phase HPLC로 분석한 실험은 이러한 결과를 더욱 확실히 뒷받침하였다. 정제된 BBS-LS를 합성 BBS-14와 비교하여 생물학적 활성을 검토한 결과 흰쥐에서 gastrin의 분비, 췌장액의 분비, 회장의 수축을 촉진하고 guinea pig 담낭의 수축을 증가시키는 등 이들 두물질이 매우 유사한 생물학적 활성을 지니고 있음을 발견하였다. 이러한 결과로 보아 한국에 서식하는 무당개구리의 피부는 서로 다른 두가지 형태의 BBS-LS를 함유하고 있으며 그 중에서 96.5%를 차지하는 BBS-LS는 합성 BBS-14와 분자적 이질성을 지니나 유사한 생물학적 활성을 지니고 있음을 알 수 있었다.

• 대한수의학회지
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• 제40권1호
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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.

• BMB Reports
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• 제54권11호
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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.

• 대한수의학회지
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• 제41권4호
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• pp.477-484
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• 2001

붕어 (Carassius auratus Linnaeus)의 장에 존재하는 소화관 내분비세포의 부위별 분포 및 출현빈도를 포유류의 peptide에 대한 10종류의 항혈청을 사용하여 면역조직화학적 방법으로 관찰하였다. 붕어의 장은 근위부에서부터 원위부까지 5 등분했으며 (Segments I~V), 대부분의 면역반응세포들은 상피부분의 상피세포들 사이 공간에서 관찰되었으며, 장 내강까지 신장되어 있는 긴 세포질돌기를 함유한 방추형의 개방형 세포 (open type cell)들이 주로 관찰되었으나, 세포질돌기 없이 원형 또는 타원형의 형태를 나타내는 폐쇄형 세포 (close type cell)들 역시 소수 관찰되었다. 본 실험에서는 somatostatin, cholecystokinin (CCK)-8 및 pancreatic polypeptide (PP) 면역반응세포들이 관찰되었으나, serotonin, glucagon, chromogranin A, secretin, vasoactive intestinal peptide (VIP), substance P 및 bombesin 면역반응세포들은 관찰되지 않았다. 한편 somatostatin 면역반응세포들은 장의 가장 근위부인 Segment I에 국한되어 극소수 관찰되었으며, CCK-8 면역반응세포들은 장의 근위부인 Segment I과 II에서 소수 또는 극소수의 빈도로 관찰되었다. PP 면역반응세포들 역시 장의 근위부에서 중간 부위인 Segment I에서부터 III에 걸쳐 중등도 또는 극소수의 빈도로 출현하였다. 이상에서 붕어 위 내분비세포들의 부위별 분포 및 출현 빈도는 다른 위가 없는 경골어류 (stomachless teleost)에서의 보고들과 유사하였으나, 독특한 분포를 나타내는 면역반응세포들 역시 관찰되었다.

• 한국동물학회지
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• 제33권3호
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• pp.276-296
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• 1990

우리 나라에 서식하는 뱀목 중 뱀과의 유혈목이, 능구렁이 및 무자치와 살모사과의 살모사, 까치살모사 및 쇠살모사를 재료로 하여 그 위장관에 출현하는 장내분비세포들 중 bombesin, CCK-8, gastrin, glucagon, insulin, PP, serotonin, somatostatin, substance P 및 VIP 등 10종류의 세포를 면역세포화학적 방법으로 염색한 후 광학현미경하에서 세포의 분포, 출현빈도, 모양 및 특징 등을 관찰하였던 바 다음과 같은 결론을 얻었다. 1. 능구렁이, 유혈목이, 무자치, 까치살모사 및 쇠살모사의 위장관 점막상피에서는 CCK-8, gastrin, PP 및 serotonin 등 4종류의 분비세포가 관찰되었으며 동물의 종 및 위장관 각 부위별에 따라 내분비세포의 다과의 차이는 다소 있었다. 2. 살모사의 위장관 점막상피에서는 CCK-8, gastrin 및 serotonin 등 3종류의 분비세포가 관찰되었다. CCK-8, gastrin 및 serotonin 세포는 위장관 전반에 걸쳐 관찰되었으며 gastrin세포는 유문부와 소장 점막에 출현하였으며 각 부위에 따른 수의 차이가 있음을 알게 되었다. 3. 위장관 점막상피에서 관찰된 장내분비세포들의 모양은 위에서는 추체형 및 난원형을 띠었고 폐쇄형이었으며 소장 및 대장 전부에서는 주로 방추형을 띤 개구형이었으나 소수는 폐쇄형도 있었다. 대장 후부 및 직장에서는 난원형의 폐쇄형이었다. 4. 본 실험에서 사용된 10종류의 항혈청 중에서 bombesin, glucagon, insulin, somatostatin, subsatance P 및 vasoactive intestinal polypeptide 항체 등에 양성반응을 보인 장내분비세포들은 관찰되지 않았다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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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.