deamino-arginine-vasopressin and Lung-Neoplasms

GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing's disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type 1a (GHSR-1a). However, there are no studies correlating the in vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing's syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients.. Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied.. Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR.. GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting in vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients.. Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and in vivo response to the secretagogue in both the CD and the EAS patients.

Topics: ACTH Syndrome, Ectopic; Adolescent; Adrenocorticotropic Hormone; Adult; Antidiuretic Agents; Carcinoid Tumor; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Hydrocortisone; Lung Neoplasms; Male; Middle Aged; Oligopeptides; Prospective Studies; Receptors, Ghrelin; Receptors, Vasopressin; RNA, Messenger; Thymus Neoplasms

We herein report a rare case of advanced lung adenocarcinoma with central diabetes insipidus due to pituitary metastasis. Although treatment with gefitinib was dramatically effective, the symptoms of diabetes insipidus did not improve. Radiotherapy for pituitary metastasis was effective to control diabetes insipidus; however, we could not cease the administration of 1-deamino-8-D-arginine vasopressin (DDAVP). It is important for physicians to positively consider radiotherapy for pituitary metastases even if favorable tumor control is achieved with chemotherapy when diabetes insipidus becomes clinically overt. Furthermore, continuous DDAVP administration may be needed to treat central diabetes insipidus.

Topics: Adenocarcinoma of Lung; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Gefitinib; Humans; Lung Neoplasms

Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance.. Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo.. In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells.. The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging.. suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.

Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Deamino Arginine Vasopressin; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Humans; Liver Neoplasms; Lung Neoplasms; Mice; Neoplasm Metastasis; Neoplasm Staging; Neovascularization, Pathologic; Receptors, Vasopressin; Xenograft Model Antitumor Assays

[V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of the compound for the management of aggressive breast cancer.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Receptors, Vasopressin; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Desmopressin (dDAVP) is a synthetic peptide analog of vasopressin with antidiuretic and hemostatic properties. Recent experimental evidence have suggested that dDAVP can inhibit metastasis formation by agonist action on V2 vasopressin receptors present in both tumor and endothelial cells. We have examined the kinetics of dDAVP effect during metastatic colonization and its potential association with hemostasis.. The experimental metastasis assay was performed by injecting F3II mammary carcinoma cells into the lateral tail vein of syngeneic female BALB/c mice.. Clinically relevant doses of dDAVP (0.3 to 2 μg/kg intravenously (i.v.)) produced a dose-dependent inhibition in the formation of lung nodules when administered during the first 24 hours after F3II tumor cell injection. The hemostatic agent tranexamic acid (10 mg/kg, i.v.) had no effect on metastasis formation in the same experimental conditions, while the anticoagulant enoxaparin (1 mg/kg, subcutaneously (s.c.)) did not modify the antimetastatic action of dDAVP. In vitro, dDAVP had a strong inhibitory effect on F3II cell colony formation.. dDAVP interferes with early metastatic disease, and direct association of this effect with hemostatic mechanisms is unlikely.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Deamino Arginine Vasopressin; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Lung Neoplasms; Mice; Mice, Inbred BALB C; Tumor Burden

Bronchuscarcinoma ist the most frequent death cause with tumor patients. At time of diagnosis the stadium is often already advanced, the patient is inoperable. We present a patient (non-smoker) with polydipsia, visual troubles and polyuria. The lab results confirmed diabetes insipidus, but the following x-rays proved multiple intracerebral spots. And also multiple spots in the lungs, the mediastinum, in the liver, the coloumn and the adrenals. Histological diagnosis was non small cell lung cancer (NSCLC).

Topics: Antidiuretic Agents; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Carcinoma, Non-Small-Cell Lung; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Palliative Care; Polyuria; Radiography, Thoracic; Radiotherapy Dosage; Vinblastine; Vinorelbine

Topics: Carcinoma, Mucoepidermoid; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Hypothalamic Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Parotid Neoplasms; Polyuria; Thirst

Tumor metastasis to the pituitary gland has been infrequently reported, and this is probably because only a small proportion of these patients are symptomatic. Most of the symptoms of this malady are related to diabetes insipidus. A 78-year-old man was diagnosed 2 years previously with stage IIIA adenocarcinoma of the lung and treated with sequential chemoradiation therapy and later with whole-brain radiation therapy because of newly developed brain metastasis; he was then admitted to our hospital with symptoms of polydipsia and polyuria. He was confirmed to have central diabetes insipidus that was caused by the pituitary metastasis from lung cancer. His symptoms resolved after treatment with desmopressin. Because of the rarity of this manifestation in lung cancer patients, we report on this case along with a brief review of the relevant literature.

Topics: Aged; Antidiuretic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Lung Neoplasms; Male; Pituitary Neoplasms; Polyuria; Radiography; Thirst

A 71-year-old man was admitted with high fever, thirst, polyposia and polyuria. After examination, lung cancer (adenocarcinoma T1NOM1, Stage IV) and central diabitus insipidus caused by pituitary metastasis of lung cancer, were diagnosed. We gave him desmopressin acetate, gamma knife surgery for pituitary metastasis and chemotherapy with paclitaxel and carboplatin, and his symptoms improved. However, his lung cancer progressed. Diabitus insipidus caused by lung cancer is rare.

Topics: Adenocarcinoma; Aged; Antidiuretic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Docetaxel; Humans; Lung Neoplasms; Male; Paclitaxel; Pituitary Neoplasms; Radiosurgery; Taxoids

Desmopressin (DDAVP) is a synthetic derivative of vasopressin with hemostatic and fibrinolytic properties that has been used during surgery in patients with bleeding disorders. Our aim was to investigate the effect of DDAVP on lung and lymph node metastatic cell colonization using a preclinical mouse mammary carcinoma model of subcutaneous tumor manipulation and surgical excision.. Female BALB/c mice bearing the highly aggressive F3II mammary carcinoma were subjected to repeated manipulations of primary tumors (0.5 kg/cm(2) during 2 min), followed (or not) by surgical excision. DDAVP was administered intravenously 30 min before and 24 h after each manipulation or surgery, at a dose of 2 microg/kg. At the end of the experiment, mice were sacrificed and necropsied.. Tumor manipulation induced dissemination to the axillary nodes and increased up to 6-fold the number of metastatic lung nodules. Perioperative treatment with DDAVP dramatically reduced regional metastasis. The incidence of lymph node involvement in manipulated animals was 12% with DDAVP and 87% without treatment (P < 0.02). Histopathological analysis of axillary nodes from DDAVP-treated animals showed sinusal histiocytosis and no evidence of cancer cells. Metastatic lung nodules were also reduced about 65% in animals treated with DDAVP (P = 0.026).. Our results suggest a potential clinical application of DDAVP in the management of breast cancer, as well as other aggressive solid tumors. DDAVP may be useful to reduce the risk of metastatic cell colonization both during and after surgical manipulation.

Topics: Animals; Axilla; Deamino Arginine Vasopressin; Disease Models, Animal; Hemostatics; Lung Neoplasms; Lymphatic Metastasis; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Time Factors

A 67-year-old man with von Willebrand's disease, was referred to our hospital for operation of the lung cancer. He underwent right upper lobectomy of the lung and mediastinal lymph node dissection under general anesthesia. Three days before surgery, 1-desamino-8-D-arginine-vasopressin (DDAVP) was infused with good response of bleeding time shortening from 6 minutes to 3 minutes. Therefore, immediately before operation, DDAVP was infused. During the operation bleeding tendency was observed. Heat-treated factor VIII concentration and fresh frozen plasma were administered. Bleeding tendency was controlled. Total blood loss was 613 ml. During intraoperative and postoperative period, factor VIII activity and von Willebrand factor (vWF) activity were kept at adequate levels (factor VIII: 105-150%; vWF: 65-225%). The postoperative course was uneventful and he was discharged 18 days after the operation.

Topics: Aged; Anesthesia, General; Deamino Arginine Vasopressin; Factor VIII; Humans; Lung Neoplasms; Lymph Node Excision; Male; Perioperative Care; Pneumonectomy; von Willebrand Diseases

Von Willebrand's disease (vWD) is one of the most common inherited hemorrhagic disorders, and there have been few reports on major thoracic surgery performed in a patient with the disease. We report a vWD patient who underwent of surgical resection of lung cancer. A 67-year-old gentleman, was diagnosed to have vWD when he was an infant, but he needed no medical treatment. Abnormal shadow in the lung was detected on a mass screening chest X-ray. We performed open biopsy, which proved the shadow to be large cell cancer, and performed right upper lobectomy and lymph node dissection. We used Contact-F, monitoring factor VIII, vWD factor and factor VIII-related antigen, during and after the operation, with a successful result.

Topics: Aged; Carcinoma, Large Cell; Deamino Arginine Vasopressin; Hemostatics; Humans; Intraoperative Care; Lung Neoplasms; Lymph Node Excision; Male; Pneumonectomy; von Willebrand Diseases

We have investigated the effects of desmopressin (DDAVP), a synthetic analog of the natural hormone vasopressin, on experimental lung colonization of mammary tumor cells using a syngeneic BALB/c mouse model. Coinjection of DDAVP (1-2 microg/kg body weight) at the time of i.v. inoculation of F3II carcinoma cells or LM3 adenocarcinoma cells significantly inhibited the formation of experimental lung metastases. In both cases, the number of pulmonary nodules was reduced about 70%. Inhibition of metastasis was also obtained with i.v. administration of DDAVP 24 h after tumor cell inoculation. Interestingly, the inhibition of lung metastasis was not due to direct cytotoxic effects of DDAVP on mammary tumor cells. The in vitro formation of multicellular aggregates in the presence of citrated plasma from control and DDAVP-treated mice was also examined. Control plasma rapidly induced a significant tumor cell aggregation. In contrast, in the presence of plasma from DDAVP-treated mice, tumor cells remained as a single cell suspension. DDAVP may help to dissolve the protective fibrin shield of circulating tumor cells. Our data suggest, for the first time, that adjuvant DDAVP therapy may impair successful implantation of circulating mammary tumor cells.

Topics: Animals; Cell Aggregation; Deamino Arginine Vasopressin; Female; Hemostatics; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C