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1.
Clin Case Rep ; 6(12): 2303-2308, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30564317

ABSTRACT

Pheochromocytomas are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

2.
J Med Case Rep ; 11(1): 32, 2017 Feb 06.
Article in English | MEDLINE | ID: mdl-28162094

ABSTRACT

BACKGROUND: Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. CASE PRESENTATION: A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. CONCLUSIONS: The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.


Subject(s)
Antithyroid Agents/therapeutic use , Graves Disease/diagnosis , Graves Disease/immunology , Immunoglobulins, Thyroid-Stimulating/blood , Methimazole/therapeutic use , Autoantibodies/blood , Graves Disease/blood , Graves Disease/drug therapy , Humans , Male , Middle Aged , Radionuclide Imaging , Receptors, Thyrotropin/blood , Thyroid Function Tests , Thyroid Gland/diagnostic imaging , Thyroid Gland/physiopathology , Thyroxine/therapeutic use , Treatment Outcome
3.
Respir Med Case Rep ; 20: 77-81, 2017.
Article in English | MEDLINE | ID: mdl-28070481

ABSTRACT

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by heterozygous germline mutations in the tumor suppressor gene MEN1, which encodes a nuclear protein, menin. MEN1 is characterized by the combined occurrence of tumors involving the pituitary gland, pancreatic islets, and parathyroid glands. Additionally, patients with MEN1 often exhibit adrenal tumors. Although most MEN1-associated tumors are benign, malignant lesions arising in these endocrine organs have been reported. Additionally, malignant diseases of non-endocrine organs concomitant with MEN1 have also been reported. Here, we report a rare case of a MEN1 patient who exhibited adrenocortical carcinoma (ACC) and lung adenocarcinoma (LAC). A 53-year-old Japanese woman was diagnosed with genetically proven MEN1 that initially manifested as parathyroid, pancreatic, and adrenal tumors. During the course of the disease, she developed LAC harboring the epidermal growth factor receptor gene mutations and cortisol-secreting ACC. Both tumors were surgically resected. The tumor cells were immunohistochemically negative for menin. Studies have suggested a causative link between MEN1 gene mutations and ACC, and menin expression may decrease in MEN1-related ACCs. In contrast, there are few reports suggesting a specific role of MEN1 gene mutations in LAC. Menin is often inactivated in the LACs of patients without MEN1. Thus, our patient's ACC probably occurred as part of MEN1, whereas the latter had no evident etiological association with her LAC. This case demonstrates the need for physicians to consider the potential development of malignant diseases originating from both endocrine and non-endocrine organs in MEN1 patients.

4.
Clin Case Rep ; 4(12): 1101-1106, 2016 12.
Article in English | MEDLINE | ID: mdl-27980741

ABSTRACT

Central diabetes insipidus (CDI) results from a deficiency of arginine vasopressin (AVP) secretion. It is treated by replacement therapy with the synthetic AVP analogue desmopressin. To prevent heart failure in patients with CDI accompanied by cardiac dysfunction, controlling sodium and water intake is essential, using the minimum effective dose of desmopressin.

5.
J Med Case Rep ; 10(1): 279, 2016 Oct 12.
Article in English | MEDLINE | ID: mdl-27729064

ABSTRACT

BACKGROUND: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. CASE PRESENTATION: A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. CONCLUSIONS: Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Adrenalectomy , Hypertension/etiology , Hypotension/etiology , Laparoscopy , Necrosis/pathology , Pheochromocytoma/diagnosis , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/surgery , Aged , Antihypertensive Agents/administration & dosage , Asian People , Blood Pressure , Catecholamines/metabolism , Chest Pain , Headache , Humans , Hypertension/physiopathology , Hypotension/physiopathology , Male , Pheochromocytoma/complications , Pheochromocytoma/surgery , Treatment Outcome
6.
Intern Med ; 55(18): 2649-58, 2016.
Article in English | MEDLINE | ID: mdl-27629962

ABSTRACT

A 73-year-old Japanese woman with untreated Graves' hyperthyroidism developed glucocorticoid-induced adrenal insufficiency (AI) after a supraphysiological dose of prednisolone therapy for bronchial asthma. Days later, she had high plasma adrenocorticotropic hormone (ACTH) levels and was expected to recover from glucocorticoid-induced AI. Her plasma ACTH levels remained high over 3 months during a physiological dose of hydrocortisone replacement. However, she suffered a further decrease in her serum cortisol level and was diagnosed with isolated adrenocorticotropin deficiency (IAD), in which bioinactive ACTH likely caused the high ACTH value. IAD should be considered as an unusual disorder associated with Graves' disease, especially in older patients.


Subject(s)
Adrenal Insufficiency/chemically induced , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/deficiency , Asthma/drug therapy , Endocrine System Diseases/chemically induced , Genetic Diseases, Inborn/chemically induced , Glucocorticoids/adverse effects , Graves Disease/drug therapy , Hydrocortisone/therapeutic use , Hypoglycemia/chemically induced , Prednisolone/adverse effects , Adrenal Insufficiency/drug therapy , Adrenal Insufficiency/physiopathology , Adrenocorticotropic Hormone/drug effects , Aged , Anorexia/blood , Anorexia/drug therapy , Antithyroid Agents/therapeutic use , Fatigue/blood , Fatigue/drug therapy , Female , Glucocorticoids/therapeutic use , Graves Disease/complications , Graves Disease/physiopathology , Humans , Hydrocortisone/blood , Prednisolone/therapeutic use , Treatment Outcome
7.
J Med Case Rep ; 10(1): 225, 2016 Aug 12.
Article in English | MEDLINE | ID: mdl-27520566

ABSTRACT

BACKGROUND: Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. CASE PRESENTATION: A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. CONCLUSIONS: The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.


Subject(s)
Acute Lung Injury/chemically induced , Adamantane/analogs & derivatives , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Nitriles/adverse effects , Pyrrolidines/adverse effects , Adamantane/adverse effects , Adult , Female , Humans , Vildagliptin
8.
Intern Med ; 55(6): 643-6, 2016.
Article in English | MEDLINE | ID: mdl-26984083

ABSTRACT

A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8°C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D.


Subject(s)
Coxsackievirus Infections/complications , Coxsackievirus Infections/diagnosis , Diabetes Mellitus, Type 1/diagnosis , Diabetic Ketoacidosis/diagnosis , Enterovirus/isolation & purification , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Acute Disease , Aged , Antibodies, Viral/blood , Coxsackievirus Infections/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/virology , Diabetic Ketoacidosis/complications , Diabetic Ketoacidosis/etiology , Enterovirus/immunology , Fatigue/etiology , Fever/etiology , Fluid Therapy/methods , Humans , Male , Polyuria/etiology , Thirst , Treatment Outcome
9.
Intern Med ; 55(5): 485-9, 2016.
Article in English | MEDLINE | ID: mdl-26935368

ABSTRACT

A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency.


Subject(s)
Autoantibodies/blood , C-Peptide/blood , Diabetes Mellitus, Type 1/blood , Glutamate Decarboxylase/blood , Insulin/metabolism , Pancreas/metabolism , Biomarkers/blood , Diabetes Mellitus, Type 1/drug therapy , Disease Progression , Female , Glutamate Decarboxylase/drug effects , Humans , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Secretion , Middle Aged , Pancreas/drug effects , Predictive Value of Tests , Treatment Outcome
10.
Intern Med ; 55(4): 389-94, 2016.
Article in English | MEDLINE | ID: mdl-26875965

ABSTRACT

A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia.


Subject(s)
Adrenocorticotropic Hormone/metabolism , Cushing Syndrome/complications , Idiopathic Pulmonary Fibrosis/etiology , Autopsy , Cushing Syndrome/drug therapy , Cushing Syndrome/physiopathology , Disease Progression , Fatal Outcome , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/physiopathology , Male , Middle Aged
11.
Intern Med ; 54(18): 2361-5, 2015.
Article in English | MEDLINE | ID: mdl-26370862

ABSTRACT

We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody-positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable.


Subject(s)
Anemia, Pernicious/complications , Diabetes Mellitus, Type 1/complications , Aged , Anemia, Pernicious/drug therapy , Anemia, Pernicious/immunology , Asian People , Autoantibodies/analysis , Diabetes Mellitus, Type 1/immunology , Diabetic Ketoacidosis/etiology , Humans , Hyperglycemia/etiology , Male , Stomach/immunology , Vitamin B 12/analogs & derivatives , Vitamin B 12/therapeutic use
13.
Pancreatology ; 5(4-5): 354-60, 2005.
Article in English | MEDLINE | ID: mdl-15980664

ABSTRACT

BACKGROUND/AIMS: Recent studies have shown an association between the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic pancreatitis (CP). We here examined the prevalence of SPINK1 mutations in Japanese patients with pancreatitis. METHODS: Genomic DNA was prepared from 80 Japanese patients with CP, 36 patients with acute pancreatitis (AP), and 165 healthy controls. All exons and the promotor region of the SPINK1 gene were amplified by the polymerase chain reaction, and directly sequenced. RESULTS: We found four types of mutation (N34S, IVS1-37T>C, -215G>A, and IVS3 + 2T>C) and two types of polymorphism (-253T>C and 272C>T). The N34S mutation cosegregated with IVS1-37T>C, and was present in 8 CP and 1 AP patients. The -215G>A mutation was in a complete linkage with IVS3 + 2T>C, and was present in 8 CP and 1 AP patients. The prevalences of [N34S; IVS1-37T>C] and [-215G>A; IVS3 + 2T>C] were significantly higher in patients with familial pancreatitis (38 and 13%, respectively) and with idiopathic CP (13 and 16%) than normal subjects (0.6 and 0%). In addition, the frequency of [N34S; IVS1-37T>C] mutation was higher in patients with autoimmune CP (33%). CONCLUSION: The SPINK1 gene mutations were associated with pancreatitis also in Japan.


Subject(s)
Carrier Proteins/genetics , Genetic Predisposition to Disease , Mutation , Pancreatitis/genetics , Acute Disease , Adolescent , Adult , Aged , Carrier Proteins/metabolism , Child , Chronic Disease , DNA/genetics , DNA Mutational Analysis , DNA Primers/chemistry , Female , Gene Frequency , Humans , Japan , Male , Middle Aged , Pancreatitis/metabolism , Pancreatitis/pathology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Trypsin Inhibitor, Kazal Pancreatic
14.
Gan To Kagaku Ryoho ; 32(6): 855-8, 2005 Jun.
Article in Japanese | MEDLINE | ID: mdl-15984531

ABSTRACT

A 73-year-old woman was admitted to our hospital for evaluation of hypochondralgia, and a thorough examination revealed an AFP producing gastric cancer with multiple liver metastases. One course of TS-1 100 mg/day for 4 weeks and discontinuation for 2 weeks was started from February, 2003. After 3 months, the level of AFP reduced remarkably from 53,700 ng/ml to the normal limit. The metastatic tumors in the liver showed regression, and after 14 months, CT scanning showed that the tumors had disappeared. Since the size of the original tumor showed no change, distal gastrectomy was performed, and curability A was achieved. We consider this rare case has significant value in terms of treatment of AFP producing gastric cancer with multiple liver metastases. We think the combination of surgery and chemotherapy such as TS-1 will lead to a better prognosis in such cases.


Subject(s)
Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/therapeutic use , Gastrectomy , Liver Neoplasms/secondary , Oxonic Acid/therapeutic use , Pyridines/therapeutic use , Stomach Neoplasms/drug therapy , Tegafur/therapeutic use , alpha-Fetoproteins/biosynthesis , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Combined Modality Therapy , Drug Administration Schedule , Drug Combinations , Female , Humans , Preoperative Care , Prognosis , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
15.
Pancreas ; 26(4): 350-6, 2003 May.
Article in English | MEDLINE | ID: mdl-12717267

ABSTRACT

INTRODUCTION: Although many experimental studies have implicated the activation of nuclear factor kappa B (NF-kappaB) as a pivotal step in the pathobiology of acute pancreatitis, no clinical investigations have been reported. AIMTo investigate the expression of NF-kappaB and its characteristics in peripheral blood mononuclear cells (PBMCs) of patient with acute pancreatitis. METHODOLOGY: Forty-five patients were prospectively enrolled. The expression of NF-kappaB in PBMCs was measured in the patients by electrophoretic mobility shift assay at admission and 14 days after the onset of acute pancreatitis. Twelve healthy individuals were also included as control subjects. RESULTS: At admission, the PBMCs from patients with acute pancreatitis showed higher levels of NF-kappaB activities than did those from control subjects. In vitro, the lipopolysaccharide (LPS) treatment of the PBMCs from the control subjects and patients with mild pancreatitis induced further activation of the NF-kappaB. The response was significantly reduced in patients with severe pancreatitis. Patients who had persistently high NF-kappaB activities, a reduced response of NF-kappaB to LPS, and a low p50p65:p50p50 ratio after LPS stimulation at 14 days developed serious systemic complications in the later clinical course. CONCLUSIONS: An alteration of the characteristics of PBMCs occurs in the early phase of acute pancreatitis and may predispose patients to a higher risk of serious systemic complications.


Subject(s)
Leukocytes, Mononuclear/metabolism , NF-kappa B/blood , Pancreatitis/blood , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Humans , Leukocytes, Mononuclear/drug effects , Lipopolysaccharides/pharmacology , Male , Middle Aged
16.
Pancreas ; 24(3): 251-7, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11893932

ABSTRACT

INTRODUCTION: Invasion and metastasis of cancer cells require cell motility and adhesion. The small GTPase Rho and one of its effector molecules ROCK regulate cytoskeleton and actomyosin contractility, and play a crucial role in cell adhesion and motility. Results of previous studies showed that the elevated activity of ROCK-1, one of the isomers of ROCK kinases, led to an increase in the activity of invasion and metastasis of cancer cell lines. AIM: To investigate the importance of ROCK-1 in cancer invasion and metastasis. METHODOLOGY: We investigated the expression of ROCK-1 in two cancer cell lines and 31 human pancreatic tissues (21 pancreatic cancers [PC] and 10 histologically normal tissues) by immunoblotting and immunohistochemistry. We also examined by haptotaxis assay whether the migratory activity of PC cells could be suppressed by treatment with the morpholino antisense oligonucleotide in vitro. RESULTS: The expression of ROCK-1 was found in 18 of 21 PC tissues (85.7%), but not in normal pancreatic tissues by immunoblotting and immunohistochemistry. Antisense oligo against ROCK-1 significantly inhibited the haptotaxis of Panc-1 in a dose-dependent manner, compared with the control oligo. CONCLUSION: These results suggest that ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration.


Subject(s)
Gene Expression Regulation/drug effects , Oligonucleotides, Antisense/pharmacology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Protein Serine-Threonine Kinases/genetics , Cell Movement/drug effects , Cell Survival/drug effects , Humans , Immunoblotting , Immunohistochemistry , Intracellular Signaling Peptides and Proteins , Oligonucleotides, Antisense/genetics , Pancreas/metabolism , Protein Serine-Threonine Kinases/physiology , Transfection , rho-Associated Kinases
17.
Pancreas ; 24(1): 34-41, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11741180

ABSTRACT

INTRODUCTION: Invasion and metastasis of pancreatic cancer (PC) require cell motility and adhesion, which depend on the activity of cytoskeleton. A cytoskeletal component indispensable for these processes is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. AIMS AND METHODOLOGY: Because the activity of myosin II is accelerated by phosphorylation of myosin II on its regulatory light chain (RLC) by myosin light chain kinase (MLCK), we used two specific MLCK inhibitors, ML-7 and ML-9, for suppression of motility and adhesion of PC cell lines. RESULTS: Both drugs were potent inhibitors, as measured by in vitro motility assay and adhesion assay. When treated with the same concentration of ML-7, the PC cells were rounded up, and the number of stress fibers was reduced markedly. The in vitro migration and adhesion of PC cells were inhibited by ML-7 and ML-9 in a dose-dependent manner, supporting a specific and competitive inhibition of MLCK by these drugs. The inhibition occurred at nontoxic concentrations. CONCLUSIONS: These results highlight the importance of myosin II in the invasion and metastasis of PC cells and suggest the possibility that blocking of myosin II activity by a specific MLCK inhibitor may be a therapeutic strategy for preventing the invasion and metastasis of PC.


Subject(s)
Enzyme Inhibitors/pharmacology , Myosin-Light-Chain Kinase/antagonists & inhibitors , Pancreatic Neoplasms/pathology , Tumor Cells, Cultured/drug effects , Azepines/pharmacology , Cell Adhesion/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Humans , Integrin beta1/analysis , Naphthalenes/pharmacology , Neoplasm Invasiveness , Neoplasm Metastasis , Pancreatic Neoplasms/metabolism
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