Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1 and ROCK2.

Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated. After androgen stimulation, we showed that AR directly activates the transcription of miR-135a2 gene by binding to an androgen response element in the promoter region. Our findings identify miR-135a as a novel effector in androgens/AR signaling. Using xenograft experiments in chick embryos and adult male mice, we showed that miR-135a overexpression decreases in vivo invasion abilities of prostate PC-3 cells. Through in vitro wound-healing migration and invasion assays, we demonstrated that this effect is mediated through downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR-135a direct target genes. In human surgical samples from prostatectomy, we observed that miR-135a expression was lower in tumoral compared with paired adjacent normal tissues, mainly in tumors classified with a high Gleason score (⩾8). Moreover, miR-135a expression is lower in invasive tumors, showing extraprostatic extension, as compared with intraprostatic localized tumors. In tumor relative to normal glands, we also showed a more frequently higher ROCK1 protein expression determined using a semi-quantitative immunohistochemistry analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to a higher ROCK1 protein expression, which could explain their invasion abilities. The highlighted relationship between miR-135a expression level and the degree of disease aggressiveness suggests that miR-135a may be considered as a prognostic marker in human PCa.

Targeting 14-3-3 sensitizes native and mutant BCR-ABL to inhibition with U0126, rapamycin and Bcl-2 inhibitor GX15-070.

Small molecule tyrosine kinase inhibitors, such as imatinib, are effective therapies for BCR-ABL-mediated human leukemias. However, clinical drug resistance occurs, which warrants development of alternative and/or complementary therapeutic strategies to target critical downstream signaling molecules. We recently demonstrated that disrupting 14-3-3/ligand association by a peptide-based 14-3-3 competitive antagonist R18 induces significant apoptosis, partially through reactivation of AKT-inhibited proapoptotic FOXO3a, in FGFR1 fusion-transformed hematopoietic cells. Here, we report that targeting 14-3-3 by R18 effectively induced significant apoptosis in Ba/F3 and K562 cells expressing BCR-ABL, similarly through liberation and reactivation of FOXO3a. Moreover, R18 sensitized BCR-ABL-transformed cells to inhibition with MEK1 inhibitor U0126, Bcl-2 inhibitor GX15-070, or mTOR inhibitor rapamycin. Treatment with these reagents potentiated R18-induced reactivation of proapoptotic FOXO3a with enhanced expression of downstream transcription targets p27(kip1) and Bim1. Furthermore, R18-induced apoptotic cell death in cells expressing diverse imatinib-resistant BCR-ABL mutants, including T315I. This inhibition was enhanced by R18 in combination with U0126 and rapamycin. Thus, our findings suggest that targeting 14-3-3 may potentiate the effects of conventional therapy for BCR-ABL-associated hematopoietic malignancies, and overcome drug resistance.

[Alveolar echinococcosis of the liver. Mass ultrasound screening in the Haut Cantal area]. / Echinococcose alvéolaire hépatique. Dépistage échographique de masse dans le haut cantal.

OBJECTIVE: Mass systematic screening for alveolar echinococcosis (AE) of the liver in the Haut Cantal endemic area. MATERIAL AND METHODS: Targeted population was composed of the members of the Mutualité Sociale Agricole of the area, from 16 to 65 years old. 2077 notifications were sent, corresponding to 20% of the population of this area, defined by a triangle between Egliseneuve d'Entraigues, Riom ès Montagne and Saint Flour. Two screening tests were performed: Elisa serology test and liver ultrasound examination. RESULTS: Participation levels were relatively low-ultrasound: 18.92%, serology: 17%. Among 350 liver examinations, 2 suspicions of AE were found: CT and serology confirmed the diagnosis in the first symptomatic patient; CT and biopsy confirmed the diagnosis in the other asymptomatic patient in whom serology was normal. CONCLUSION: Ultrasound screening showed at least a 0.57% prevalence of AE, i.e., 2 cases out of 350. This low rate however confirms that Haut Cantal is an endemic area, but with a lower incidence rate than in other endemic areas.

[Prevalence and morphology of pineal cysts discovered at pituitary MRI: review of 1844 examinations]. / Prévalence et morphologie des kystes épiphysaires: à propos de 1844 IRM hypophysaires.

PURPOSE: To evaluate the frequency, morphology and clinical long term evolution of pineal cysts depicted on MRI. PATIENTS AND METHODS: one thousand eight hundred and forty four (1 532 women and 126 men) MRI examinations were retrospectively reviewed. Coronal and sagittal spin echo T1 weighted sequences without and with gadolinium injection were performed, completed with spin echo T2 weighted images when a cystic sellar lesion was suspected. A pineal cyst was diagnosed as a rounded well defined lesion, with fluid signal in an enlarged pineal gland. Follow-up examinations were performed to evaluate the efficacy of the treatment of the sellar lesion. RESULTS: Twenty one epiphyseal cysts (1.27%) were diagnosed in 20 women (1.31%) and one man (0.79%). Their size was 1,2 +/- 0,4 cm (0,3 to 2 cm). They were asymptomatic. In 10 patients, follow-up MRI examinations did not show any change in size. During the clinical follow-up, these twenty-one patients remained asymptomatic (6 months to 5 years). CONCLUSION: The incidental detection of a pineal cyst at MRI is not exceptional. This lesion's pattern appears characteristic and their reputation of benignity is confirmed in our study.

[Pituitary gland MRI and Cushing disease: report of 14 operated patients]. / IRM hypophysaire et maladie de Cushing: à propos de 14 patients opérés.

PURPOSE: Evaluate the MR sensibility for detection and localisation of ACTH-secreting microadenomas of the pituitary gland. PATIENTS: and method. The MRI studies of the pituitary gland, performed before transsphenoidal surgical exploration, about 14 patients who present clinical and biological signs of Cushing disease, were reviewed retrospectively. We have always used unenhanced sagittal and coronal spin-echo T1 sequences, and coronal T1 after injection of gadolinium (1 Tesla). RESULTS: The global sensibility for detection of an adenoma was 100% (84 to 92% when the lesional localisation was considered). The injection of gadolinium increased the sensibility of 38 to 42% according the readers. 7 to 14% of the lesions were isointense after injection. The estimation of lesional size after injection was the nearer to the surgical results. The indirect sign most frequently seen (35.7 to 64.3%) was focal bulging of the sellar diaphragm. The only differences between the different radiologists, statistically significant, concerned the lesional size before injection and location of the lesion in the sagittal plane. CONCLUSION: This study confirmed the good sensibility of contrast-enhanced MRI in detection of ACTH-secreting microadenomas. The anatomo-radiological correlations are nevertheless incomplete.

Localisation of members of the notch system and the differentiation of vibrissa hair follicles: receptors, ligands, and fringe modulators.

Hair vibrissa follicle morphogenesis involves several cell segregation phases, in the dermis as well as in the epidermis. The expression of Notch-related genes, which are well established mediators of multiple cell segregation events in Drosophila development, was studied by in situ hybridisation during embryonic mouse vibrissa follicle morphogenesis and the first adult hair cycle. The results show that two receptors, Notch1 and -2, three ligands, Delta1, Serrate1, and -2, and the three Fringe regulators, Lunatic, Manic, and Radical, are expressed in different locations and morphogenetic stages. First, the appearance of hair vibrissa primordia involves the expression of complementary patterns of Notch2, Delta1, and Lunatic Fringe in the dermis and of Notch1, Serrate2, and Lunatic Fringe in the epidermis. Second, this expression pattern is no longer found after stage 3 in the dermis. Meanwhile, in the epidermis, the expression of Notch1, Serrate2, and Lunatic Fringe before the formation of the placode may be involved in determining two populations of epidermal cells in the developing follicle. Third, complementary expression patterns for Notch1, Manic, and Lunatic Fringe, as well as Serrate1 and -2 as previously shown (Powell et al., 1998), are progressively established from stage 4 of embryonic development both in the outer root sheath and in the hair matrix. These patterns are consistent with the one found in the adult anagen phase. During the hair vibrissa cycle, Notch1 and Manic Fringe display temporal and spatial changes of expression, suggesting that they may intervene as modulators of trichocyte activities.

Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

PURPOSE: A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. RESULTS: A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P <.001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone (n = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in myelosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine. CONCLUSION: The CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

Infrapopliteal percutaneous transluminal angioplasty for limb salvage.

PURPOSE: To evaluate long-term results of infrapopliteal percutaneous transluminal angioplasty (PTA) for limb salvage. MATERIAL AND METHODS: A retrospective study of 71 consecutive infrapopliteal PTAs in 49 patients with rest pain (n = 20) or ulceration (n = 29) was conducted. In 18 patients, surgical minor amputation or debridment was also performed. RESULTS: Technical success was achieved in 45 patients. Four failures necessitated 2 amputations. One patient died in the postoperative course. Global morbidity rate was 16%, including minor complications in 5 patients and major vascular complications in 3 patients. After technical success during the follow-up (median duration 21 months), restenoses occurred in 4 patients, of whom 3 had a successful re-PTA (clinical success rate 72%). Survival, primary patency, secondary patency and limb salvage rates were, respectively, 75%, 81%, 88% and 87% after 3 years. The only positive predictive factor for primary patency was the presence of diabetes mellitus. CONCLUSION: Infrapopliteal PTA is a safe and effective procedure, allowing good patency and limb salvage rates with low mortality and morbidity.

Spiral CT quantification of aorto-renal calcification and its use in the detection of atheromatous renal artery stenosis: A study in 42 patients.

PURPOSE: To investigate whether a correlation exists between aortic and renal arterial calcifications detected with spiral CT and significant angiographic renal artery stenosis (RAS). METHODS: Forty-two patients (mean age 67 years, range 37-84 years), of whom 24 were hypertensive, prospectively underwent abdominal helical CT and aortic and renal arteriography. The 3-mm thickness CT scans (pitch = 1) were reconstructed each millimeter. A manual outline of the renal artery including its ostial portion was produced. Calcific hyperdensities were defined as areas of density more than 130 HU. CT data were compared with the presence or absence of RAS on angiography (24 cases); hypertension and age were taken into account (Mann-Whitney U-test). RESULTS: CT detection and quantification appeared to be reliable and reproducible. We did not find any correlation between aortic and renal arterial calcifications and RAS, even for the patients above 65 years, with or without hypertension. There was no correlation either between calcifications and hypertension in patients without RAS. CONCLUSION: In this population, aortic and renal arterial calcifications have no predictive value for RAS.

Visualisation of the portal flows by porto-scanner.

This study presents a retrospective analysis of 15 portal vein CT scans, conducted for the evaluation of hepatic metastasis in patients suffering from colorectal cancer, with the aim of verifying in vivo the presence of laminar flow as reported by Pironcof. After selective catheterization of the superior mesenteric artery, CT scans were performed during opacification of the portal vein. Different flows were identified by the incomplete opacification they induced in the portal vein. Splenic flows could always be identified, however right colic and superior mesenteric flows were only seen in 3 cases (20%) and gastrocolic flow in 2 (13.6%). Even though incremental (i.e. slower than helical) the CT acquisitions allowed the flows to be viewed by modifying the visualisation window. In vivo evidence of laminar flow is provided which supports Pironcof's experimental observations.

Phase II trial of escalated dose of tirapazamine combined with cisplatin in advanced malignant melanoma.

A phase II study was undertaken to determine the efficacy of tirapazamine combined with cisplatin in patients with metastatic melanoma between April 1996 and April 1997. Tirapazamine 390 mg/m2, administered i.v. over 2 h, followed in 1 h by cisplatin 75 mg/m2 over 1 h, were used every 21 days to treat chemotherapy-naive patients with metastatic melanoma. Objective tumor measurements were used to assess efficacy of the regimen. NCI common toxicity criteria were used to grade toxicities. Forty-eight patients with metastatic melanoma of cutaneous or mucosal origin, none with symptomatic brain metastasis, were treated. Nine patients had a partial response, with an overall response rate of 20% (95% confidence interval: 9-33%). The median duration of response was 6 months. Grade 3 nausea, vomiting, anorexia, muscle cramps and fatigue occurred in fewer than 10% of patients. Neutropenia and thrombocytopenia were rare. This outpatient single-day administered tirapazamine-cisplatin regimen has definite activity in chemotherapy-naive patients with metastatic melanoma. Further studies in combination with other agents active against this disease are warranted.

Endovascular Doppler guide wire in renal arteries. Correlation with angiography in 20 patients.

RATIONALE AND OBJECTIVES: To evaluate the feasibility of endovascular Doppler recording in renal arteries and to compare the reliability of Doppler parameters for detection of renal artery stenosis. METHODS: The authors examined 36 renal arteries in 20 patients with a 0.018" endovascular flow wire. Peak systolic velocity and the renal artery-to-aortic peak were measured in the main renal artery. From intrarenal waveforms, acceleration, acceleration time, and the renal resistive index were obtained. Spectral analysis with consensus scoring of early systolic peak was also performed. RESULTS: Twelve significantly stenosed renal arteries and 26 normal renal arteries were examined with the Doppler guide wire, without complications. Peak systolic velocity was the only parameter significantly different in renal artery stenosis (P = 0.037). Peak systolic velocity also differed significantly between hypertensive and normotensive patients. Tardus parvus was specific for severe renal artery stenosis. CONCLUSIONS: Endovascular Doppler is a safe and accurate method for the determination of velocity measurements and may be useful during percutaneous renal artery revascularization.

Dynamic magnetic resonance imaging of the female pelvis: radio-anatomy and pathologic applications. Preliminary results.

Dynamic MRI of the pelvis was performed in 16 young nulliparous, normally continent women. The examinations were performed in the dorsal decubitus position. Using Turbo-Flash scans (acquisition time: 2.1 sec), sagittal images were obtained at rest and with maximal pelvic straining. The sacral promontory-subpubic (PSP) and the subpubic-subsacral axes (SPSS) measured respectively 80.5 degrees and 30 degrees in relation to the horizontal plane, without a statistically significant difference between rest and straining. A marked deformation of the posterior wall of the bladder was observed in 13 cases and the bladder neck was frontally deformed in 10 cases. With straining, the base of the bladder did not descend beyond 15 mm below the SPSS, and the cervix stayed at least 14 mm above the SPSS. These were established as the normal criteria for pelvic assessment. 20 multiparous patients (mean age 65 years), referred for urinary stress incontinence and/or prolapse, were investigated using the criteria previously established. The PSP, SPSS, and vaginal angle measured 80.95 degrees, 30.57 degrees, and 69.69 degrees respectively in relation to the horizontal. No statistically significant difference was detected between straining and rest conditions. The angle of the uterus in relation to the horizontal was 57.36 degrees at rest and 65.90 degrees in straining with a difference that was statistically significant. In six patients, the base of the bladder descended more than 1.5 cm while straining and in seven patients the cervix descended at least 1.4 cm below the SPSS while straining, both statistically significant differences. Overall, between our control and study populations, there were no significant differences between PSP and SPSS measured on straining and at rest. However, differences were detected in the vaginal angle, bladder-base position, and cervical position. These results suggest the potential substitution of MRI for colpocystography.

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

[Hepatocellular carcinoma in cirrhosis: semeiology and performance of magnetic resonance imaging and lipiodol computed tomography]. / Carcinome hépatocellulaire sur cirrhose: sémiologie et performances de l'imagerie par résonance magnétique et de la tomodensitométrie après artériographie lipiodolée.

OBJECTIVES: a) Describe hepatocellular semiology in magnetic resonance imaging and lipiodol computerized tomography in patients with cirrhosis, who are candidates for surgery; b) Clarify the respective roles of magnetic resonance imaging and lipiodol computerized tomography in hepatocellular detection. METHODS: Twenty four patients with suspected hepatocellular carcinoma underwent successive magnetic resonance imaging and lipiodol computerized tomography. Thirty-four of the 67 lesions seen by lipiodol computerized tomography and 28 of 52 lesions seen by magnetic resonance imaging were confirmed histologically. RESULTS: In lipiodol computerized tomography, 44% of hepatocellular carcinomas had a dense and homogeneous pattern; 24% had a homogeneous but slightly dense pattern. Sixteen distinct deposits were described: 4 were confirmed as hepatocellular carcinoma and 12 were not controlled histologically. In magnetic resonance imaging 57% of hepatocellular carcinomas have a high intensity on T1 and T2 weighted spin echo images, 38% were hyperintense on T2 and hypo or isointense on T1 weighted images. Eighty-six percent of hyperintense T1 and T2 weighted images were hepatocellular carcinoma. When the gold standard was histology, lipiodol computerized tomography sensitivity (81%) was higher than magnetic resonance imaging (68%). When the gold standard was lipiodol computerized tomography, the sensitivity of magnetic resonance imaging was 47 +/- 12%. CONCLUSIONS: a) The sensitivity of lipiodol computerized tomography was better than resonance magnetic imaging; b) the homogeneous and slightly dense pattern corresponded to a hepatocellular carcinoma in 50% of cases; c) on magnetic resonance imaging any lesions with high intensity on T1 and T2 spin echo images strongly suggests hepatocellular carcinoma; d) if surgical resection after ultrasonography is being considered, the second step should be an magnetic resonance imaging.

[Radio-anatomic study of the angle of origin of dysplastic renal arteries]. / Etude radio-anatomique de l'angle d'origine des artères rénales dysplasiques.

PURPOSE: To compare the angulation at the origin of dysplastic renal arteries compared to atherosclerotic renal arteries, in order to improve the technique for percutaneous transluminal angioplasty of FMD. MATERIALS AND METHODS: Retrospective analysis of 40 aortograms in patients who underwent renal angioplasty for dysplastic stenosis, with comparison with 45 control aortograms (with or without atherosclerotic lesions of the renal arteries). The angle of implantation of the renal arteries was measured relative to the aortic axis in the frontal plane, taking into account only the angulation of its proximal segment. We identified three types of kidneys with regard to their position relative to the renal artery ostium. RESULTS: The angle of implantation of dysplastic renal arteries is significantly sharper compared with the control group (63.8 degrees vs 80.9 degrees, p = 0.0001), irrespective of the side. The angulation did not correlate with the position of the kidney or the direction of the renal artery, suggesting a congenital origin. CONCLUSION: The angle of implantation of the dysplastic renal arteries relative to the aortic axis in the frontal plane is sharper than the angle measured in non dysplastic renal arteries.

Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS: Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION: The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.

Differential expression pattern of the three Fringe genes is associated with epidermal differentiation.

Epidermal differentiation, as keratinocytes go through different layers to the skin surface, may imply a differential activation of Notch transmembrane proteins. In mouse, as recently shown in Drosophila, Notch activation by its ligands may be modulated by Fringe secreted proteins. Therefore, we cloned the mouse homolog of Radical-fng, synthesized riboprobes for Lunatic-fng, Manic-fng, and Radical-fng, and examined their expression during epidermal differentiation. Expression of all three genes is differentially activated during embryonic epidermal stratification. Manic-fng and Lunatic-fng are expressed in the basal layer, whereas Lunatic-fng is expressed in the granular layer and Radical-fng is restricted to the most differentiated nucleated layer. This expression decreases by a few days postnatally and can be reactivated by retinoic acid treatment, which triggers a new distribution of Fringe transcripts and a thickening of the granular layer. Therefore, Manic, Lunatic, and Radical Fringe by modulating the Notch pathway may play a key role in defining the different steps of keratinocyte differentiation.

[Regression of a focal nodular hyperplasia after stopping oral contraceptives]. / Régression d'une hyperplasie nodulaire focale après arrêt d'une contraception orale.

The complete regression of a focal nodular hyperplasia of the liver with typical MRI patterns 5 years after withdrawal of oral contraceptives was observed. Effects of oral contraceptives on this tumor's evolution and appropriate imaging by MRI are discussed.

Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor that stimulates epithelial cell motility, invasion and morphogenesis. Its receptor is a transmembrane tyrosine kinase encoded by the Met proto-oncogene. Several studies have suggested a possible role for HGF/Met in tumor development and progression. To investigate the potential roles of Met in human lung cancer biology, we have studied the mRNA and protein expression of Met in normal lung tissue, primary non-small cell lung carcinoma (NSCLC), and NSCLC cell lines. The results indicated a differential pattern of Met expression among various subtypes of NSCLC. The majority of squamous cell carcinoma (SQCC), either in vivo or in vitro, expressed Met mRNA and its protein product at levels much lower than or similar to normal lung tissue or bronchial epithelium. Moreover, SQCC characteristically over-expressed a variant Met mRNA which corresponds to a 5' partially deleted transcript produced by alternative splicing. In contrast, the expression of Met mRNA and its protein product in adenocarcinoma (ADC) and large cell undifferentiated carcinoma were more heterogeneous. Overexpression was demonstrated in approximately 35% and 20% of these subtypes of NSCLC, respectively. Among ADC, intermediate to high levels of Met immunoreactivity correlated with greater degree of tumor differentiation. Furthermore, an accentuation of Met immunoreactivity was often noted in cancer cells at the advancing edge of tumors. These findings support a role for Met in lung cancer cell invasion and differentiation in vivo, but its expression and functions may be modified by the differentiation phenotype of the tumor cells.