Pharmacological characterization of N-tert-butyl-N’-[2-(4’-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time

in Journal of Pharmacology and Experimental Therapeutics (The) (2004), 309(2), 498-505

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined ... [more ▼]

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F-2)-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50+/-5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16+/-0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia. [less ▲]

Dentin matrix protein 1 is expressed in human lung cancer

in Journal of Bone and Mineral Research (2003), 18(8), 1506-1512

We have previously shown that breast and prostate cancers express bone matrix proteins. DMPI expression was evaluated in 59 human lung cancer samples at the protein and mRNA levels. It was detectable in ... [more ▼]

We have previously shown that breast and prostate cancers express bone matrix proteins. DMPI expression was evaluated in 59 human lung cancer samples at the protein and mRNA levels. It was detectable in 80% of the cases, suggesting a potential role for DMP1 in tumor progression and bone metastasis. Introduction: Previously, we and others have shown that bone extracellular matrix proteins such as bone sialoprotein (BSP) and osteopontin (OPN) are expressed in various types of cancer that are characterized by a high affinity for bone including breast, prostate, and lung adenocarcinoma. Based on biochemical and genetic features, BSP, OPN, dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP) have been recently classified in a unique family named SIBLING (small integrin-binding ligand, N-linked glycoprotein). Therefore, we investigated whether DMPI could also be detected in osteotropic cancers. Materials and Methods: We first used a cancer array for evaluating the relative abundance of DMP1 transcript in a broad spectrum of human cancer tissues. This screening showed that DMP1 was strongly detectable in lung tumors compared with normal corresponding tissue. In a second step, we used an immunophosphatase technique and a specific polyclonal antibody directed against DMPI to examine the expression of DMP1 in 59 human non-small cell lung cancer samples, including 29 squamous carcinoma, 20 adenocarcinoma, and 10 bronchioloalveolar carcinoma. Student's t-test was used to determine the statistical significance of immunostaining scores between the lung cancer histological groups studied and between cancer and normal lung tissues. Results: Our results show that DMP1 is detectable in 90% of the adenocarcinoma and squamous carcinoma analyzed while 8 of 10 bronchioloalveolar specimens were negative. DMP1 immunostaining intensity and extent scores were significantly higher in adenocarcinoma (p = 0.0004) and squamous carcinoma (p < 0.0001) samples compared with adjacent normal lung tissue. In situ hybridization experiments confirmed that DMP1 mRNA is localized in lung cancer cells. Conclusion: In this study, we show that a third SIBLING protein is ectopically expressed in lung cancer. The role of DMPI in lung cancer is largely unknown. Further studies are required to determine the implication of this protein, next to its sisters SIBLING proteins, in tumor progression and bone metastasis development. [less ▲]

BM-613, a new thromboxane A2 antagonist, is characterized by a preferential activity on platelet thromboxane A2 receptors

in Blood (2003)

Gastric collision between a papillotubular adenocarcinoma and a gastrinoma in a patient with Zollinger-Ellison syndrome.

in Virchows Archiv : An International Journal of Pathology (2002), 441(5), 462-5

We report a unique case of a gastric collision tumor composed of an intramural gastrin-secreting tumor and a papillotubular adenocarcinoma of the intestinal type discovered at autopsy in a patient with ... [more ▼]

We report a unique case of a gastric collision tumor composed of an intramural gastrin-secreting tumor and a papillotubular adenocarcinoma of the intestinal type discovered at autopsy in a patient with Zollinger-Ellison syndrome. There was extensive metastatic dissemination of the neuroendocrine component to regional lymph nodes and to the liver. The unusual macroscopical, histological, and immunohistochemical features of this case and its specific clinical setting are discussed. [less ▲]

Une dorsalgie malheureusement tenace

in Revue Médicale de Liège (2002), 57(5), 270-273

The etiological diagnosis of chronic thoracic pain is wide, from benign mechanical disorders to tumors. Reaching the exact diagnosis in often time consuming. Despite the availability of new techniques of ... [more ▼]

The etiological diagnosis of chronic thoracic pain is wide, from benign mechanical disorders to tumors. Reaching the exact diagnosis in often time consuming. Despite the availability of new techniques of imagery, a meticulous clinical history and physical examination remain mandatory. They will lead the exploration. Idiopathic intercostal neuralgia does not exist. [less ▲]

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy

in European Urology (2001), 40(5), 495-503

Objectives: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a ... [more ▼]

Objectives: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. Methods: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. Results: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p <0.05) but failed to predict the pathological stage (p >0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p <0.05), with exact agreement rates < 40%. Conclusions: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RR Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens. Copyright (C) 2001 S. Karger AG, Basel. [less ▲]

Incidence des perturbations psychoendocriniennes au centre interdisciplinaire de l’andropause (CIA) du CHU de Liège : bilan des 7 premiers mois d’activité

in Annales d'Endocrinologie (2001), 62(4), 178

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy.

in European Urology (2001), 40(5), 495-503

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a ... [more ▼]

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. METHODS: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p<0.05), with exact agreement rates <40%. CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens. [less ▲]

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy

Conference (2000)

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface ... [more ▼]

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface associated molecule whose increased expression is associated with the aggressiveness of a variety of human cancers. We recently showed that 67LR detection in PC tissues from radical prostatectomy (RP) specimens was an independent predictor of biochemical relapse in patients with clinically localized PC (JNCI, 89:1224-1227, 1997). In this study, we assessed 67LR detection in diagnostic biopsies as a predictor of biochemical relapse after RP. MATERIAL & METHODS: A total of 151 patients with clinically confined PC underwent RP. PC tissue sections from both biopsy and RP specimens were immunohistochemically analyzed for 67LR expression. The importance of 67LR expression was evaluated according to the intensity and extent of the staining. Preoperative and postoperative clinicopathological parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5% and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p=0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens, with exact agreement rates <40% (p<0.05). CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main raisons for discordant prognostic results depending on whether 67LR expression was evaluated either in biopsies or in RPs. [less ▲]

Thrombangiitis Obliterans (Buerger's Disease): Still a Limb Threatening Disease

in Acta Chirurgica Belgica (1997), 97(5), 229-36

A series of 29 well-documented and properly analysed patients with thrombangiitis obliterans (Buerger's disease) is presented. The diagnosis of Buerger's disease was based on following criteria: smoking ... [more ▼]

A series of 29 well-documented and properly analysed patients with thrombangiitis obliterans (Buerger's disease) is presented. The diagnosis of Buerger's disease was based on following criteria: smoking history, onset before the age of 50 years, infrapopliteal arterial occlusive disease, either upper limb involvement or phlebitis migrans, absence of atherosclerotic risk factors other than smoking. In the last 10 years (1986-1996), we identified 29 patients who met these rigid criteria. There were 24 men and 5 women, aged 32.4 years at the moment of the disease first clinical symptom. The cumulative tobacco use averaged 16 pack-years for each patient. The initial symptom was limited gangrene of a toe (n = 9) or a finger (n = 2), foot claudication (n = 6), calf claudication (n = 3), rest pain (n = 3), migratory superficial phlebitis (n = 4), and Raynaud phenomenon (n = 2). Angiography and/or Doppler ultrasound revealed digital, pedal and calf artery involvement in all patients, with proximal extension in ten patients (femoropopliteal in ten, including three cases with external iliac artery involvement). Seven patients had also evidence of upper limb involvement. Histologic proof was available in only seven patients. Only nine patients completely stopped smoking. Treatment was exclusively medical in five cases. Twenty-four underwent sympathectomy (20 at lumbar, and four at thoracic level), with good immediate result in 16. In 11 patients a vascular reconstruction was done (eight femorocrural and three iliofemoral bypasses), with a patency rate of only 36% at two years. Amputation was required in 16 patients (a mean of 2.7 amputations per patient) at one or more levels: toe (n = 19), forefoot (n = 5), below knee (n = 8), above knee (n = 2), finger (n = 3). Two patients ended up with bilateral leg amputation. Overall, 23% (7/30) of the patients required major leg amputation during the course of the disease. Disease progression was moderately related to continued tobacco use. Buerger's disease still entails considerable risk of major amputation. Complete abstinence from tobacco use is crucial to expect stabilization of the process. However, in advanced stages of the disease and despite cessation of smoking recurrent episodes of ischaemia or tissue loss are not excluded. [less ▲]