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1.
Animals (Basel) ; 12(13)2022 Jun 21.
Article in English | MEDLINE | ID: mdl-35804499

ABSTRACT

Approximately 300 species of cnidarian jellyfish have been reported in Japanese waters. However, many specimens remain unidentified. In this study, taxonomic investigations, including morphological observations and molecular 16S phylogenetic analyses, were conducted on unknown specimens collected off Oarai, Sagami Bay, and Tosa Bay, Japan. The specimens have the following morphological characteristics: distinct peaks in jelly above the base of the manubrium, a red band on the manubrium, and cylindrical marginal bulbs, each with an abaxial ocellus that is common to the family Halimedusidae. However, the specimens can be distinguished from other Halimedusidae species by their eight radial canals, eight tentacles with numerous stalked nematocyst knobs, and eight nematocyst tracks on the exumbrella. Moreover, molecular phylogenetic analyses revealed that the Kimura two-parameter distance between the specimens and other Halimedusa species was 0.066-0.099, which is considered to represent intergeneric variability. Based on this result, we described it as a new species and established a new genus for taxonomic stabilization. We also emended the diagnostic characters of the family Halimedusidae owing to the establishment of the new genus. Halimedusidae comprises five species in four genera. This paper provides taxonomic keys for the identification of species in the family Halimedusidae.

2.
Clin Case Rep ; 9(5): e04118, 2021 May.
Article in English | MEDLINE | ID: mdl-34026158

ABSTRACT

Long-acting somatostatin analogs, including lanreotide slow release (LAN-SR) and octreotide long-acting release (OCT-LAR), can improve hypoglycemia in insulinoma. LAN-SR may be more beneficial in some patients with insulinoma than OCT-LAR.

3.
Pediatr Int ; 61(9): 852-858, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31283864

ABSTRACT

BACKGROUND: Human calmodulin (CALM) gene mutation has been reported to be related to inherited arrhythmia syndromes, but the genotype-phenotype relationship remains unclear. METHODS AND RESULTS: We report here a 4-year-old boy who had cardiac arrest while playing in a kindergarten playground. Cardiopulmonary resuscitation was initiated immediately. Eleven minutes after the cardiac arrest, ambulance crews arrived and an automated external defibrillator was attached. His heart rhythm, which was ventricular fibrillation (VF), was returned to sinus rhythm after only one shock delivery. The boy was brought to hospital by air ambulance. During transfer, electrocardiogram (ECG) showed transient VF. On arrival, chest radiograph showed a cardiothoracic ratio of 55% without pulmonary congestion. A 12-lead ECG showed a normal sinus rhythm, biphasic T wave, and prolongation of the corrected QT interval. On ECG, VF was preceded by torsade de pointes or frequent polymorphic premature ventricular contractions (PVC). Echocardiography showed a normal heart structure with decreased cardiac function. On the second day of hospitalization, ECG showed remarkable QT prolongation, T-wave alternans, and frequent PVC. Thereafter, propranolol was started. The ECG showed rapid improvement of QT prolongation and T-wave abnormality. Genetic test indicated a CALM2 mutation, and he was diagnosed with long QT syndrome-15 (LQT15). CONCLUSIONS: CALM mutations cause long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and idiopathic VF. This patient with a CALM2 p.N98S mutation had both phenotypes of LQTS and CPVT.


Subject(s)
Calmodulin/genetics , Long QT Syndrome/diagnosis , Long QT Syndrome/genetics , Mutation , Child, Preschool , Genetic Markers , Humans , Male
4.
J Obstet Gynaecol Res ; 41(12): 1991-4, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26311610

ABSTRACT

Pancytopenia in the first trimester is very rare. A 33-year-old multiparous woman presented with nausea, loss of appetite, and bodyweight loss of 7.4 kg at 9(1/7) weeks of gestation due to hyperemesis gravidarum. Her laboratory data demonstrated pancytopenia involving white blood cell count of 3500/µL, a hemoglobin level of 9.8 g/dL, and a platelet count of 10.5 × 10(4)/µL. An extensive investigation into the causes of the pancytopenia detected true hyperthyroidism: thyroid-stimulating hormone, <0.02 µU/mL; free triiodothyronine, 11.25 pg/mL; free thyroxine, 4.74 ng/dL; and anti-thyroid-stimulating hormone receptor antibodies, 12.2 IU/L. Propylthiouracil was started at a dose of 300 mg/day at 10(5/7) weeks of gestation, which resulted in the normalization of her blood parameters and concomitant improvements in her free triiodothyronine and free thyroxine levels at 12(0/7) weeks of gestation. Pancytopenia in the first trimester might be indicative of hidden hyperthyroidism.


Subject(s)
Hyperthyroidism/complications , Pancytopenia/etiology , Pregnancy Complications/etiology , Adult , Female , Humans , Hyperthyroidism/drug therapy , Pregnancy , Pregnancy Trimester, First , Propylthiouracil/therapeutic use
5.
J Surg Case Rep ; 2015(5)2015 May 07.
Article in English | MEDLINE | ID: mdl-25952954

ABSTRACT

A 72-year-old woman with a history of rectal cancer was admitted to our hospital to undergo thyroidectomy and left adrenalectomy. She had undergone low anterior resection and regional lymph node dissection for rectal cancer 52 months pre-admission (T3 N1 M0, stage IIIb according to International Union Against Cancer tumor-node-metastasis), and she had also undergone metastasectomy for lung metastases and right adrenal gland metastasis after the rectal surgery. Follow-up computed tomography scans detected nodules in the bilateral lobes of the thyroid gland and in the left adrenal gland. Subtotal thyroidectomy and left adrenalectomy were performed, and pathological examination revealed metastases of rectal cancer to the thyroid gland and left adrenal gland.

6.
Int Surg ; 100(1): 58-62, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25594640

ABSTRACT

A 57-year-old woman without any past medical history underwent abdominoperineal resection for rectal cancer in our department. On postoperative day 15, the patient complained of sudden abdominal pain, and high fever was noted in addition to the appearance of erythema around the stoma. The diagnosis of phlegmon was made, and antibiotic infusion was started. However, a few days later, the patient developed hypovolemic shock with hypoalbuminemia and hemoconcentration. Fasciotomy was performed to exclude the necrotizing fasciitis, though all cultures were negative. Upon exclusion of the differential diagnoses, idiopathic systemic capillary leak syndrome (ISCLS) was diagnosed. She was successfully treated with massive fluid infusion under ventilation and continuous hemodiafiltration. Here, we report the first case of ISCLS that occurred during the postoperative period of colorectal surgery.


Subject(s)
Capillary Leak Syndrome/diagnosis , Postoperative Complications/diagnosis , Rectal Neoplasms/surgery , Abdomen/surgery , Capillary Leak Syndrome/etiology , Female , Humans , Middle Aged , Perineum/surgery , Postoperative Complications/etiology , Rectum/surgery
7.
Crit Care ; 16(1): R33, 2012 Feb 28.
Article in English | MEDLINE | ID: mdl-22373120

ABSTRACT

INTRODUCTION: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. METHODS: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. RESULTS: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00940654.


Subject(s)
Antipyretics/adverse effects , Body Temperature/drug effects , Critical Illness/mortality , Critical Illness/therapy , Fever/mortality , Sepsis/mortality , Aged , Body Temperature/physiology , Female , Fever/drug therapy , Humans , Male , Middle Aged , Prospective Studies , Sepsis/drug therapy , Treatment Outcome
8.
Gan To Kagaku Ryoho ; 38(10): 1627-32, 2011 Oct.
Article in Japanese | MEDLINE | ID: mdl-21996957

ABSTRACT

We investigated the effectiveness of prophylactic FOLFOX after curative resection of synchronous metastases in patients with colorectal cancer (CRC). Clinicopathological information including postoperative chemotherapy, such as a therapeutic regimen, relapse-free survival (RFS), site of recurrence, etc., was retrospectively analyzed in 116 CRC patients with synchronous distant metastases, and 63 patients with metachronous metastases who had received surgery in our hospital between 2000 and 2009. Fifty-three patients (84%) out of 63 without adjuvant chemotherapy, and 38 (83%) out of 46 patients that received oral or intravenous 5-fluorouracil (5-FU) (alone or with leucovorin (LV)or isovorin) developed recurrent tumor(s) afterwards. The median RFSs were 119 and 281 days, respectively. By contrast, a single patient among 6 who underwent FOLFOX (up to 12 therapeutic courses) showed recurrence 476 days after surgery. The RFS of the FOLFOX was significantly higher than that of the 5-FU (+LV) or surgery alone (p=0. 03, p=0. 007, respectively). In conclusion, the FOLFOX regimen is more beneficial for CRC patients with synchronous metastasis as adjuvant chemotherapy than 5-FU (+LV) or other followup strategies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , Middle Aged , Neoplasm Metastasis/drug therapy , Organoplatinum Compounds/therapeutic use , Recurrence , Retrospective Studies
9.
Oncology ; 80(1-2): 84-91, 2011.
Article in English | MEDLINE | ID: mdl-21677451

ABSTRACT

OBJECTIVES: The prophylactic effect of FOLFOX regimen, a standard regimen for unresectable colorectal cancer (CRC), was investigated in the adjuvant setting of CRC cases with distant metastases. METHODS: The study population included 116 CRC patients with synchronous metastases and 91 patients with metachronous metastases who had undergone curative operation in our hospital between 2000 and 2009. Clinicopathological parameters of CRC, postoperative chemotherapeutic regimen, recurrence rate, and relapse-free survival (RFS) were analyzed retrospectively. RESULTS: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only 1 (17%) among 6 patients who underwent FOLFOX treatment showed recurrence. The FOLFOX group exhibited significantly improved RFS as compared to the 5-FU (+ LV) or surgery-alone group (p = 0.03, p = 0.007, respectively). On the other hand, in patients with metachronous metastases, tumor-relapse rate and RFS were not significantly influenced by post-metastasectomy therapies. CONCLUSIONS: In this retrospective analysis, the adjuvant administration of FOLFOX appeared to reduce the risk of relapse in a small group of CRC patients with synchronous metastases. Prospective randomized trials will be required to confirm the benefits of this management strategy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Colorectal Neoplasms/surgery , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Logistic Models , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Retrospective Studies , Survival Rate
10.
Eur J Cancer ; 44(3): 383-90, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18060766

ABSTRACT

Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5x10(7) HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs' membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. Our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer.


Subject(s)
Brain Neoplasms/prevention & control , Cancer Vaccines/administration & dosage , Colorectal Neoplasms/prevention & control , Endothelium, Vascular/immunology , Neovascularization, Pathologic/prevention & control , Umbilical Veins/immunology , Adult , Aged , Brain Neoplasms/blood supply , Colorectal Neoplasms/blood supply , Cytotoxicity, Immunologic/drug effects , Cytotoxicity, Immunologic/immunology , Dendritic Cells/immunology , Endothelium, Vascular/cytology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Interferon-gamma/metabolism , Male , Middle Aged , Neoplasm Metastasis/prevention & control , Neoplasm Recurrence, Local/prevention & control , Pilot Projects , T-Lymphocytes, Cytotoxic/immunology , Treatment Outcome , Umbilical Veins/cytology
11.
Masui ; 56(4): 418-20, 2007 Apr.
Article in Japanese | MEDLINE | ID: mdl-17441449

ABSTRACT

An 88-year-old man was admitted to the intensive care unit after the ingestion of 150 mg of dehydrocodeine. The ECG showed severe brodycardia and he was diagnosed as sick sinus syndrome. The recovering of sinus node function took 5 days after the ingestion. The complication observed suggests that transient hypoxia induced by ingestion of high dose DHC had affected sinus node.


Subject(s)
Analgesics, Opioid/adverse effects , Codeine/analogs & derivatives , Neuralgia, Postherpetic/drug therapy , Sick Sinus Syndrome/chemically induced , Aged, 80 and over , Analgesics, Opioid/administration & dosage , Codeine/administration & dosage , Codeine/adverse effects , Electrocardiography , Humans , Male , Sick Sinus Syndrome/diagnosis , Sick Sinus Syndrome/therapy
12.
Eur J Cancer ; 42(5): 668-73, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16427272

ABSTRACT

Id genes (inhibitor of DNA binding/differentiation) play important roles in tumour growth. We have previously described crucial roles of Id gene over-expression in endothelial cells for tumour angiogenesis. Here, we have evaluated direct effects of Id gene down-regulation on tumour cells, namely on cell proliferation, motility, and adhesion to lung microvasculature during haematogenous metastasis. For this purpose, Id genes were stably down-regulated by RNA interference in human colorectal cancer cells. These cells showed delayed proliferation, inhibited motility and decreased expression of integrin alpha6 and consequently reduced adhesion to lung microvasculature in mice. Static adhesion assays and laminar flow assays revealed decreased laminin binding capacity of these cells, and blocking experiments confirmed that it could be attributed to decreased expression of integrin alpha6. The present results indicate important roles of Id genes in tumour cells during early steps of haematogenous metastasis and suggest dual effects from their therapeutic inhibition.


Subject(s)
Colorectal Neoplasms/genetics , Hematologic Neoplasms/etiology , Inhibitor of Differentiation Proteins/genetics , Animals , Cell Adhesion Molecules , Cell Line, Tumor , Cell Transformation, Neoplastic , Down-Regulation , Female , Flow Cytometry , Humans , Laminin/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude
13.
Cancer Sci ; 95(1): 85-90, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14720332

ABSTRACT

Overcoming immune tolerance of tumor angiogenesis should be useful for adjuvant therapy of cancer. We hypothesized that vaccination with autologous endothelium would induce an autoimmune response targeting tumor angiogenesis. To test this concept, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of Colon-26 cancer. Vaccination with autologous HSEs induced both preventive and therapeutic anti-tumor immunity that significantly inhibited the development of metastases. ELISA revealed an immunoglobulin response involving IgM and IgG subclasses. These antibodies had a strong affinity for antigens of both murine and human endothelium, and lyzed endothelial cells in the CDC assay. Flow-cytometry and chromium-release cytotoxicity assay revealed a specific CTL response against endothelial cells, which were lyzed in an effector: target ratio-dependent manner. Neither antibodies nor CTLs reacted with Colon-26. The effect of autologous HSEs was more pronounced than that of xenogeneic human umbilical vein endothelial cells (HUVECs), which were tested in the same experimental setting. Our results suggest that vaccination with autologous endothelium can overcome peripheral tolerance of self-angiogenic antigens and therefore should be useful for adjuvant immunotherapy of cancer.


Subject(s)
Cancer Vaccines/therapeutic use , Colonic Neoplasms/drug therapy , Endothelium/immunology , Lung Neoplasms/secondary , Neovascularization, Pathologic/drug therapy , Animals , Autoantigens/immunology , Colonic Neoplasms/pathology , Colonic Neoplasms/prevention & control , Cytotoxicity Tests, Immunologic , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Lung Neoplasms/drug therapy , Mice , Neoplasm Invasiveness , T-Lymphocytes, Cytotoxic/immunology , Umbilical Veins/cytology
14.
J Immunol Methods ; 295(1-2): 183-93, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15627623

ABSTRACT

Analysis of specific properties of tumor endothelium should be useful for development of novel antiangiogenic strategies. However, the isolation of pure endothelial cells from tumor tissues is still a fundamental problem. In this study, we have attempted to develop a reliable method for the isolation of endothelial cells from murine tumors. We found that the labeling with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated-low density lipoprotein (Dil-Ac-LDL), commonly used for this purpose, can result in the contamination of isolated endothelium by macrophages due to the overlapping staining patterns of these two distinct cell types. Therefore, we chose the CD16, which is expressed on macrophages but not endothelial cells, to better distinguish them when labeled with Dil-Ac-LDL. By using this method, we obtained pure populations of endothelial cells and macrophages from murine colorectal cancer tissues, showing characteristic morphological and functional properties of the either cell type. The endothelial cells were long spindle-shaped, spread on gelatin, formed tube-like structures on Matrigel and expressed MECA-32 but not CD68. In contrast, the macrophages were round-shaped, partially spread on gelatin, formed unorganized aggregates on Matrigel and expressed CD68 but not MECA-32. The additional analysis of normal and tumor tissues revealed a positive correlation between the relative numbers of tumor endothelial cells and macrophages, calculated as % total cells, as well as the respective relative number and tumor weight. The present method is hoped to be useful for the evaluation of tumor angiogenesis and antitumor immunity.


Subject(s)
Cell Separation/methods , Endothelial Cells/cytology , Lipoproteins, LDL/metabolism , Macrophages/cytology , Receptors, IgG/metabolism , Animals , Colonic Neoplasms/metabolism , Endothelial Cells/metabolism , Flow Cytometry/methods , Humans , Macrophages/metabolism , Mice , Microscopy, Confocal
15.
J Gastroenterol ; 38(3): 229-37, 2003.
Article in English | MEDLINE | ID: mdl-12673445

ABSTRACT

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is reported to be highly expressed in tumors and inflammatory tissues, but its expression and role in inflammatory bowel disease (IBD) are still unclear. In this study we examined the location and tissue density of cells immunoreactive for PD-ECGF in the colonic mucosa of IBD. METHODS: Paraffin-embedded sections of colonic tissue from patients with ulcerative colitis (UC) or Crohn's disease (CD) were immunostained for PD-ECGF. As controls, noninflamed mucosa of IBD, as well as normal colonic mucosa from patients with colorectal cancer, were used. Also, cancer tissues were evaluated. In addition, changes in the expression of PD-ECGF in human umbilical vein endothelial cells (HUVEC) after treatment with inflammatory cytokines and angiogenic factors, as well as after coculture with colon cancer cell lines, were evaluated by flow cytometry. RESULTS: In normal colonic mucosa and noninflamed mucosa of IBD, PD-ECGF expression was negligible. In inflamed colonic mucosa, strong expression was observed, predominantly in macrophages and fibroblasts. Vascular endothelial cells of the inflamed colonic mucosa, but not of normal colonic mucosa or of neoplastic tissues, stained for PD-ECGF, and the microvessel density was significantly increased in the severely inflamed mucosa. Flow cytometry demonstrated that PD-ECGF was constitutively expressed in HUVEC. Inflammatory cytokines and vascular endothelial growth factor (VEGF) increased its expression, whereas basic fibroblast growth factor (bFGF) decreased it. Coculture with colon cancer cell lines in direct contact, but not in those without contact, also resulted in an important decrease in the expression of PD-ECGF in HUVEC. CONCLUSIONS: Autocrine production of PD-ECGF by endothelial cells may be a mechanism of inflammatory angiogenesis, but not tumor angiogenesis, and may be particularly important for the maintenance of damaged vasculature in IBD.


Subject(s)
Colitis, Ulcerative/metabolism , Colonic Neoplasms/metabolism , Crohn Disease/metabolism , Thymidine Phosphorylase/metabolism , Endothelium/metabolism , Flow Cytometry , Humans , Immunohistochemistry , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Umbilical Veins/metabolism
17.
Surg Today ; 32(4): 343-50, 2002.
Article in English | MEDLINE | ID: mdl-12027200

ABSTRACT

PURPOSE: In the present study, we investigated the effect of troglitazone, a selective ligand and agonist of PPAR-gamma, on the metastatic potential of human colon cancer cells. METHODS: High- and low-PPAR-gamma expression clones of the colon cancer cell line, HT29, namely clones 21 and 3 respectively, were used. We investigated the effect of troglitazone on the proliferation, on the adhesion to extracellular matrix proteins and on the synthesis of matrix metalloproteinases (MMPs) of colon cancer cells. RESULTS: Troglitazone inhibited the proliferation of both subclones, in a dose-dependent manner, and the inhibitory effect correlated with the level of PPAR-gamma expression. Troglitazone strongly inhibited the production of MMP-7, an enzyme associated with invasiveness of cancer cells, by both subclones. In addition, troglitazone caused a strong decrease in the adhesion of clone 21 to extracellular matrix (ECM) proteins, laminin and type IV collagen. This effect was independent of beta1-integrins expression CONCLUSION: In addition to inhibition of cancer cell growth, troglitazone had an inhibitory effect on two important events associated with the metastatic potential of cancer cells, production of MMPs and adhesion to ECM proteins. Consequently, troglitazone is a promising agent for the treatment and prevention of colon cancer metastasis.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Adhesion/physiology , Chromans/pharmacology , Colonic Neoplasms/physiopathology , Extracellular Matrix Proteins/physiology , Matrix Metalloproteinase 7/biosynthesis , Thiazoles/pharmacology , Thiazolidinediones , Apoptosis , Blotting, Western , Cell Adhesion/drug effects , Cell Division/drug effects , Collagen Type I/physiology , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Fibronectins/physiology , Flow Cytometry , Humans , Integrins/metabolism , Laminin/physiology , Receptors, Cytoplasmic and Nuclear/agonists , Receptors, Cytoplasmic and Nuclear/metabolism , Transcription Factors/agonists , Transcription Factors/metabolism , Troglitazone , Tumor Cells, Cultured
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