The introduction of peptide receptor radionuclide therapy (PRRT) to the Philippines has allowed for novel approaches in the management of neuroendocrine tumors (NETs). This case report details the management of a 66-year-old Filipino man diagnosed with metastatic pancreatic NET after biopsy and staging with Ga-68 DOTATATE PET-CT. After poor response to somatostatin analogue therapy, the patient was advised to undergo PRRT. Upon completing four cycles of PRRT with Lu-177 DOTATATE, the metastatic hepatic lesions showed resolution and the pancreatic tail tumor exhibited regression, allowing the patient to undergo surgical resection of the primary tumor. On follow-up, he was declared to be in remission with good quality of life and no imaging evidence of recurrence. The case underscores the diagnostic and therapeutic utility of radiolabeled somatostatin analogues along with the importance of a multidisciplinary approach in the management of an initially unresectable metastatic pancreatic NET
Receptors, Peptide ; Pancreatic Neoplasms ; Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.
Neuroendocrine Tumors ; Quality of Life ; Receptors, Peptide ; Receptors, Somatostatin ; Somatostatin

OBJECTIVETo analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations.

METHODSPROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS.

RESULTSOf these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients.

CONCLUSIONPROKR2 may be the susceptibility gene of PSIS.

To explore the role of intrapulmonary neuropeptides in the development of airway hyperresponsiveness, we established an animal model of airway hyperresponsiveness (AHR) in rabbits by using ozone exposure. With the model, after test of the mechanics of respiration and bronchoalveolar lavage assay, the levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the lungs were determined by radioimmunoassay, and the expression of mRNA coding receptors of these two neuropeptides was evaluated by reverse transcriptional-polymerase chain reaction (RT-PCR). At the same time, the distribution of VIP receptor-1 (VIPR1) and CGRP receptor-1 (CGRPR1) in lung tissues and its time-course were examined by in situ hybridization. The results showed: (1) in ozone-stressing groups, airway resistance increased significantly and typical inflammatory pathological changes were observed in pulmonary tissue slides, including neutrophil and eosinophil infiltration, mucus exudation and bronchial epithelial cells (BECs) shedding; (2) with elongation of ozone exposure, the levels of VIP and CGRP in the lungs increased at first, reaching a peak on d 2 to 4, then decreased slowly, and CGRP peaked somewhat earlier than VIP; (3) mRNA expression of the two neuropeptide receptors in the lungs changed in a similar manner like VIP and CGRP, but the high level of mRNA expression of VIPR1 lasted longer than that of CGRPR1; and (4) in situ hybridization for neuropeptide receptors demonstrated that, in unstressed control, VIPR1 and CGRPR1 positive cells appeared in the airway epithelium, pulmonary interstitial and focal areas of airway and vascular smooth muscles. With the elongation of ozone exposure, hybridization stained deeper and the majority of positive cells were located around the vessels and bronchus except a few in the alveoli. At 8 d, only a small number of positive cells were seen in the lungs. From the results, it is concluded that ozone-stressing can induce the development of AHR, in which VIP and CGRP may play important roles. That implies, through binding to CGRPR1, CGRP stimulates an early inflammation response which contributes in cleaning up of irritants, while VIP exerts a later dampening of pulmonary inflammation response. These two neuropeptides may play sequential and complementary roles in the development of AHR.
Animals ; Bronchi ; pathology ; Bronchial Hyperreactivity ; chemically induced ; metabolism ; Bronchoalveolar Lavage Fluid ; Calcitonin Gene-Related Peptide ; metabolism ; Epithelium ; metabolism ; Lung ; metabolism ; Ozone ; Rabbits ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Receptors, Vasoactive Intestinal Peptide ; metabolism ; Vasoactive Intestinal Peptide ; metabolism

At present, surgery has become one of the treatments for type 2 diabetes, but it is still unclear about the therapeutic mechanism. Many experiments has proved that the anatomical and physiological structure has been altered leading to significant changes related to the secretion of gastrointestinal hormones and neuropeptides. These molecular are related to the metabolism of glucose, functions of islet cells and sensitivity of insulin. Intensive studies of glucagon-like peptide-1 (GLP-1) play an important role in the surgical treatment of diabetes and now it has gained increasing recognition. However, GLP-1 must be combined with GLP-1 receptor (GLP-1R) to execute its function. In this paper we reviewed the role of GLP-1 and its receptor in the mechanism of metabolic surgery.
Diabetes Mellitus, Type 2 ; surgery ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Receptors, Glucagon

Calcitonin gene-related peptide (CGRP) play a key role in some physiological and pathological progresses. The latest studies indicate that CGRP might involve in some disease progress and has a close relation with wound healing. It is significant to further investigate and then apply it to clinical diagnosis and therapy as well as forensic pathology.
Animals ; Calcitonin Gene-Related Peptide/physiology* ; Forensic Medicine ; Humans ; Receptors, Calcitonin Gene-Related Peptide/physiology* ; Wound Healing

PURPOSE: We analyzed the expression of vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), VIP receptor 1 (VIPR1), VIP receptor 2 (VIPR 2) and PACAP receptor (PACAPR) genes in human neuroblastoma, neuroblastoma cell line, human stomach cancer, and human stomach cancer cell lines using RT-PCR and Sourthern hybridization. The results should permit identification of potential clinical applications for VIP and PACAP. METHODS: We isolated RNA from 1 neuroblastoma cell line, 8 stomach cancer cell lines, 13 neuroblastoma, and 10 stomach cancer tumor specimens. And then we performed RT-PCR, Sourthern hybridization, and sequencing. RESULTS: We detected the RNAs coding for VIP, VIPR1, VIPR2, PACAP, and PACAPR in 1, 11, 2, 12, and 13 out of 13 neuroblastoma tumor specimens, respectively. VIP and PACAPR RNA was expressed in SKNSH. VIPR1 RNA was expressed in 4 of 8 the stomach cancer cell lines and 6 of 10 stomach cancer tumor specimens. CONCLUSION: VIP/PACAP RNA and VIP/PACAP receptors RNA were expressed in SKNSH and neuroblastoma tumor specimens. VIPR1 was expressed in stomach cancer cell lines and tumor specimens. The present results suggested that VIP/PACAP analogues could be a candidate as the growth inhibitor of neuroblastoma and stomach cancer.
Adenylyl Cyclases* ; Cell Line ; Clinical Coding ; Humans ; Neuroblastoma* ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Peptide* ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Vasoactive Intestinal Peptide ; RNA ; Stomach Neoplasms* ; Stomach* ; Vasoactive Intestinal Peptide

BACKGROUND: Neuroimmunocutaneous system alteration can be responsible for the induction and maintenance of the inflammatory process of psoriasis. OBJECTIVE: This study was carried out to examine the expression of Substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin (SOM), neutral endopeptidase (NEP), SP receptor, and CGRP receptor in psoriatic lesions. METHODS: A skin biopsy was obtained from 10 psoriatic patients and 10 normal control subjects. Confocal laser scanning microscopy was performed. RESULTS: The SP and CGRP receptors consistently increased in psoriatic lesions, compared to the normal controls. CONCLUSION: The increased expression of neuropeptides and their receptors may be involved in the pathogenesis of psoriasis.
Biopsy ; Calcitonin Gene-Related Peptide ; Humans ; Microscopy, Confocal ; Neprilysin ; Neuropeptides* ; Psoriasis ; Receptors, Calcitonin Gene-Related Peptide ; Receptors, Neuropeptide ; Skin ; Somatostatin ; Substance P

BACKGROUND: The present study was aimed to determine the pathophysiological implications of local atrial natriuretic peptide (ANP) system in the kidney in two- kidney, one clip (2K1C) hypertension. METHODS: Rats were made 2K1C hypertensive, and their mRNA expressions of ANP and natriuretic peptide receptors (NPR) were determined in the clipped and contralateral kidneys by reverse transcription-polymerase chain reaction. RESULTS: The expression of ANP was decreased in the clipped kidney and increased in the contralateral kidney. Similarly, the expression of both NPR-A and NPR-C was decreased in the clipped kidney and increased in the contralateral kidney. CONCLUSION: These findings indicate a differentially-altered ANP system in the clipped and the contralateral kidneys in 2K1C hypertension.
Animals ; Atrial Natriuretic Factor ; Hypertension* ; Kidney* ; Rats ; Receptors, Peptide ; RNA, Messenger

Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various antigens associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. Furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based carrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the carrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications.
Antibodies, Monoclonal ; Compliance ; Half-Life ; Peptides ; Radioisotopes* ; Radiopharmaceuticals ; Radiotherapy ; Receptors, Peptide