Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.     

随意皮瓣术后内皮素变化及其受体阻滞剂对皮瓣微循环的影响

目的:探讨随意皮瓣术后内皮素(ET)水平变化及内皮素受体阻滞剂BQ-123(A选择性)对随意皮瓣微循环的影响.方法:SD大鼠背部肉膜下形成随意皮瓣,测皮瓣组织ET的变化趋势.分用药组(BQ-123组)和对照组(生理盐水组),测皮瓣存活率,取材进行HE染色光镜检查,使用激光多谱勒血流仪测量皮瓣血运情况.结果:皮瓣术后ET水平急剧上升,24 h内维持较高水平.术后第10天,用药组皮瓣的存活率显著高于对照组.HE染色光镜检查见用药组组织损害较对照组小.激光多谱勒测量发现用药组较对照组激光多谱勒血流量相对值(LDF)下降少,恢复快.结论:皮瓣术后ET水平急剧上升,并维持较高水平,内皮素受体阻滞剂BQ-123(ETA高度选择性)可以阻断ET作用途径,有利于改善皮瓣微循环.     

Expression of CC Chemokine Ligand 20 and CC Chemokine Receptor 6 mRNA in Patients with Psoriasis Vuigaris

Itiswell knownthatimmune inflammatorymechanism playsanimportantroleinpsoriasis .Therelationshipbetweenchemokine ,receptorsandpsori asishasbeenconfirmed[1] .CCchemokineligand 2 0(CCL2 0 )isanewmemberinthefamilyof β chemokineandalsotheonlyligandofCCchemoki…     

Characterization of high-affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC-3 and DU-145: Internalization of receptor bound 125I-(Tyr4) bombesin by tumor cells

Specific receptors for bombesin/gastrin releasing peptide (GRP) on the androgen-independent human prostate cancer cell lines PC-3 and DU-145 were characterized. No specific binding of ¹²⁵I-[Tyr⁴]-bombesin to the androgen-dependent human prostate cancer cell line LNCaP was detectable. The binding of ¹²⁵I-[Tyr⁴]-bombesin to PC-3 and DU-145 cells was found to be time- and temperature-dependent, saturable, and reversible. Scatchard analysis revealed a single class of binding sites with high affinity (K_d 9.8 × 10^?11 M for PC-3, and 9.1 × 10-¹¹ M for DU-145 cells at 25°C) and with a binding capacity of 44,000 binding sites/cell and 19,000 binding sites/cell, respectively. Bound ¹²⁵I-[Tyr⁴]-bombesin was rapidly internalized by PC-3 cells. The nonhydrolyzable GTP analog GTP-gamma-S caused a dose-dependent inhibition of ¹²⁵I-[Tyr⁴]-bombesin binding to PC-3 and DU-145 cells, indicating that a G-protein (guanine nucleotide-binding protein) couples the bombesin receptor to intracellular effector systems. Bombesin and GRP(14-27) inhibited the binding of ¹²⁵I-[Tyr⁴]-bombesin to both cell lines in a dose-dependent manner with inhibition constants (K_i of 0.5 nM and 0.4 nM, respectively. Both cell lines express the bombesin/GRP preferring bombesin receptor subtype, since, in displacement studies, neuromedin B was more than 200 times less potent than bombesin and GRP(14-27) in inhibiting the binding of ¹²⁵I-[Tyr⁴]-bombesin. Two synthetic bombesin/GRP antagonists, RC-3095 and RC-3110, powerfully inhibited the specific binding of ¹²⁵I-[Tyr⁴]-bombesin with K_i 0.92 nM and 0.26 nM on PC-3 cells, and 3.3 nM and 0.89 nM on DU-145 cells, respectively. These findings indicate that the PC-3 and DU-145 human prostate cancer cell lines possess specific high-affinity receptors for bombesin/GRP, and are suitable models for the evaluation of the antineoplastic activity of new bombesin/GRP antagonists in the treatment of androgen-independent prostate cancer. © 1994 Wiley-Liss, Inc.     

Modification of the Phe3 aromatic moiety in delta receptor-selective dermorphin/deltorphin-related tetrapeptides Effects on opioid receptor binding

The previously described cyclic delta opioid receptor-selective tetrapeptide H-Tyr-d -Cys-Phe-d -Pen-OH (JOM-13) was modified at residue 3 by incorporation of both natural and unnatural amino acids with varying steric, electronic, and lipophilic properties. Effects on mu and delta opioid receptor binding affinities were evaluated by testing the compounds for displacement of radiolabeled receptor-selective ligands in a guinea pig brain receptor binding assay. Results obtained with the bulky aromatic 1-Nal³ and 2-Nal³ substitutions suggest that the shape of the receptor subsite with which the side chain of the internal aromatic residue interacts differs for delta and mu receptors. This subsite of either receptor can accommodate the transverse steric bulk of the 1-Nal³ side chain but only the delta receptor can readily accept the more elongated 2-Nal³ side chain. Several analogs with pi-excessive heteroaromatic side chains in residue 3 were examined. In general, these analogs display diminished binding to mu and delta receptors, consistent with previous findings for analogs with residue 3 substitutions of modified electronic character. Several analogs with alkyl side chains in residue 3 were also examined. While delta receptor binding affinity is severely diminished with Val³, Ile³, and Leu³ substitutions, Cha³ substitution is very well tolerated, indicating that, contrary to the widely held belief, an aromatic side chain in this portion of the ligand is not required for delta receptor binding. Where possible, comparison of results in this delta-selective tetrapeptide series with those reported for analogous modification in the cyclic delta-selective pentapeptide [d -Pen², d -Pen⁵]enkephalin (DPDPE) and linear pentapeptide enkephalins reveals similar trends.     

结直肠癌中雄激素受体及其与临床病理学特征关系的研究

应用放射性配基结合分析法，检测了４０例结直肠癌及部分癌旁正常粘膜组织中的雄激素受体（ＡｎｄｒｏｇｅｎＲｅｃｅｐｔｏｒ，ＡＲ），同时分析了ＡＲ水平与临床病理学变化的关系。证实结直肠癌ＡＲ数目（３３．７±２３．３ｆｍｏｌ／ｍｇ蛋白）明显低于癌旁５ｃｍ以外粘膜（５３．９±３２．４ｆｍｏｌ／ｍｇ蛋白），Ｐ＜０．０１，而其亲和力则无变化；结直肠癌时ＡＲ数目变化与女性、直肠癌、高分化癌及早期癌关系密切。提示ＡＲ与结直肠癌关系密切，本实验为临床上结直肠癌的诊断及内分泌治疗提供了初步资料。     

Subcellular localization of the inositol 1,4,5-triphosphate receptor, P400, in the vestibular complex and dorsal cochlear nucleus of the rat

The subcellular localization of the inositol 1,4,5-trisphosphate receptor protein, P₄₀₀, was studied in the vestibular complex, an area to which Purkinje cells project, as well as in neurons of the dorsal cochlear nucleus and in ectopic Purkinje cells of adult rat brain. The receptor was demonstrated by electron microscopical immunocytochemistry using the avidin-biotin peroxidase complex procedure, with the monoclonal antibody 4C11 raised against mouse cerebellar inositol 1,4,5-trisphosphate receptor protein. Immunoreactivity was found in preterminal fibres and terminal boutons in the nuclei of the vestibular complex, generally associated with the subsurface systems and stacks or fragments of smooth endoplasmic reticulum. Ectopic Purkinje cells and cartwheel cells of the dorsal cochlear nucleus also displayed immunoreactivity, but this was much less intense in the latter. The results of the present study suggest that this receptor protein, involved in the release of Ca²⁺, is located in sites that enable it to influence the synthesis, transport and release of neurotransmitters.     

Characterization of an anti-idiotypic MoAb bearing an internal image of the receptor-binding epitope of cholera toxin.

A mouse anti-cholera toxin (CT) MoAb, mAb1, specific for the GM1-binding epitope of CT, was used to raise a syngenic anti-idiotypic MoAb, mAb2. Purified mAb2 was specific for mAb1 as shown by latex particle counting immunoassay and ELISA. Several experiments of competition between mAb2 and CT for binding to mAb1 demonstrated that mAb2 bore an internal image of the GM1-binding epitope of CT. Binding of mAb2 to GM1 unambiguously corroborated the mAb1-paratopic specificity of mAb2. Furthermore, mAb2 acted as a CT-surrogate antigen: rabbits injected with mAb2 produced some anti-CT antibodies, Ab3, which resembled mAb1 in specificity as expected. The potential use of this mAb2 as vaccine or as prophylactic agent to prevent CT from binding to its cellular receptor is discussed.     

THE ROLE OF P_1-PURINERGIC RECEPTORS IN THE SPINAL MECHANISMS OF ACUPUNCTURE ANALGESIA

It has been extensively proved that electro-acupuncture elicit analgesia in bothextensive areas and local region via supraspinal structures and spinal cord.The present investigationwas to study the role of P_1-purinergic receptors in the spinal mechanisms of weak electroacupuncture-induced analgesia.Leg withdrawal latency(LWL)to noxious radiant heat focused on the ankle regionwas used to assess the effects of acupuncture and that of P_1-purinergic(adenosine)receptor antago-nists,theophylline and caffeine on the electro-acupuncture(EA)analgesia.EA prolonged the LWLby 16.7%±20.3%,with an after-effect lasting about 15 min.Both theophylline and caffeineblocked the EA-induced prolongation of LWL in a dose-dependent manner at the doses of 1.6-16 mg/kg.These results suggest that P_1-purinegic receptor is involved in the spinal mechanisms of weak EAproduced analgesia in the rat.     

In vitro and in vivo effects of BT563, an anti-interleukin-2 receptor monoclonal antibody

Abstract BT563, a murine anti-IL-2R MoAb, was found to be more potent than anti-Tac in inhibiting proliferation in the mixed lymphocyte reaction. Results obtained with 33 B3.1 in these experiments were similar to those with BT563. The anti-IL-2R MoAb 2A3 was shown to be a suitable agent for monitoring the effect of BT563 on peripheral blood. IL-2R-positive cells were not detected in peripheral blood samples from 1 h after the first dose until 8 days after the last dose. Plasma trough levels were measured in patients receiving 5 or 10 mg daily. The administration of BT563 to allograft recipients did not lead to clinically significant side effects.