[Cranial suture ultrasound for reducing radiation exposure in diagnosis of craniosynostosis in young children]. / Ul'trazvukovoe issledovanie shvov cherepa kak mera snizheniya luchevoi nagruzki v diagnostike kraniosinostozov u detei rannego vozrasta.

Currently, there are no standards for examining patients with suspected craniosynostosis. CT of the brain with 3D skull reconstruction is a common approach to diagnose craniosynostosis in many hospitals. This technique in pediatric patients is associated with a high dose of ionizing radiation and prompts searching for other diagnostic methods. OBJECTIVE: To generalize an experience of cranial suture ultrasound and compare diagnostic capabilities of various ultrasound devices. MATERIAL AND METHODS: We retrospectively analyzed data of cranial suture ultrasound in 49 patients under the age of 14 months with a suspected craniosynostosis. All patients underwent expert-class ultrasound. Of these, 10 patients underwent middle-class ultrasound. Age of these patients ranged from 2 to 10 months. RESULTS: According to ultrasound data, we have found 48 synostotic sutures in 42 patients. There were 2 inaccurate results among these 48 sutures. In both cases, expert-class ultrasound confirmed partial closure of cranial sutures while 3D CT revealed their complete closure. Sensitivity and specificity of technique were 95.8% and 100%, respectively. Both expert- and middle-class ultrasound revealed synostotic sutures in 10 children under 1 year old. CONCLUSION: Our data have shown that ultrasound of cranial sutures may be a first-line imaging technique. This method has high sensitivity and specificity in pediatric patients. Moreover, middle-class ultrasound devices may be used for diagnosis.

[Intracranial meningiomas in children]. / Vnutricherepnye meningiomy detskogo vozrasta.

Meningiomas are rare in children and distinguished from the tumors in adults by clinical and biological aspects. Moreover, some histological forms and localizations are even casuistic in adults. There were 178 patients younger 18 years old with brain tumors. All patients underwent surgery at the pediatric department for 5-year period. Meningiomas were diagnosed in 5 cases that accounted for 2.8% of the total number of brain tumors in children. The authors reported children with intracranial meningiomas and discussed certain features of the course of disease in these patients.

[Neuroendoscopic interventions using an Nd-YAG laser for multilevel hydrocephalus: treatment results for 10 patients]. / Neiroéndoskopicheskie vmeshatel'stva s ispol'zovaniem Nd-YAG-lazera pri mnogourovnevoi gidrotsefalii: rezul'taty lecheniia 10 patsientov.

INTRODUCTION: Treatment or multilevel hydrocephalus is a complex problem. Neuroendoscopic interventions, make it possible to combine minimal invasiveness with the possibility of fenestration of several cysts during one procedure and thereby eliminate multi-level occlusion. We present our the experience of using a neodymium YAG laser (Nd-YAG laser) as an additional tool to improve the treatment results of patients with non-communicating hydrocephalus. MATERIAL AND METHODS: This study included 10 patients aged from 5 months to 8 years who underwent endoscopic interventions with the use of rigid endoscope with frameless navigation. A surgical laser with a radiation wavelength of 1.064 µm was used as the main tool for fenestrating the walls of the cysts. RESULTS: 13 endoscopic laser interventions were performed in 10 patients with multilevel hydrocephalus. In 3 children, the two-stage treatment was chosen in due to the impossibility of simultaneous fenestration of all cysts. The interval between procedures was 1 month in two cases and 11 months in one case. We managed to compensate for cerebrospinal fluid disturbances in each patient, positive dynamics in the condition was noted. The duration of postoperative stay averaged 8 days (from 4 to 13 days). There were no deaths in the study group. All patients were discharged in good condition. Average follow-up duration was 14 months (from 8 to 25 months). During the observation, the condition of the patients remained stable; there was no need for repeated operations. CONCLUSION: Combined use of bypass operations, endoscopic techniques and neural navigation may improve the results of treatment of patients with multilevel hydrocephalus. Data presented in this article demonstrates the safety and effectiveness of the clinical use of laser radiation as an additional tool for interventions in patients with this condition.

A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.

Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and results A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P < 0.05) International Knee Documentation Committee (mean 39 to > 79 P < 0.05) and Knee injury and Osteoarthritis Outcome Score (64.5 to >89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures.

[Factors of endoscopic third ventriculostomy efficacy in infants with obstructive hydrocephalus under one year of age]. / Faktory éffektivnosti éndoskopicheskoi ventrikulostomii dna III zheludochka u detei do odnogo goda s okkliuzionnoi gidrotsefaliei.

Endoscopic surgery for obstructive hydrocephalus in children is an alternative to shunts. Currently, the efficacy of endoscopic third ventriculostomy (ETV) in infants up to one year of age is increasingly discussed among neurosurgeons. To increase the efficacy of ETV, many surgeons raise the question: what factors may affect the efficacy of this procedure in the younger age group? OBJECTIVE: To study the factors affecting the efficacy of ETV. MATERIAL AND METHODS: A total of 88 ETVs were performed in infants under one year of age in our clinic in 2012-2016. Subsequently, 43 (48.9%) children underwent CSF shunting, and one child underwent repeated ETV. The mean time until the appearance of clinical signs of stoma closure was 3.9 months (116 days). RESULTS: The procedure was most effective in the case of congenital obstructive hydrocephalus (64.5% of successful operations) and also in children over the age of 6 months (63.6% of successful operations). The efficacy in post-hemorrhagic hydrocephalus was 40%. The efficacy in grade 4 intraventricular hemorrhage was lowest and amounted to 25%. The total efficacy of ETV in children under one year of age in our study was 51.1%. CONCLUSION: In the case of congenital obstructive hydrocephalus, the efficacy of ETV is maximal and amounts to 64.5%. To achieve the highest efficacy of ETV in infants under one year of age, careful selection of patients at the preoperative stage is necessary, with allowance for many factors affecting treatment outcome.

[Shunt-induced craniosynostosis: topicality of the problem, choice of the approach, and features of surgical treatment]. / Shunt-indutsirovannyi kraniosinostoz: aktual'nost' problemy, vybor taktiki, osobennosti khirurgicheskogo lecheniia.

RATIONALE: Shunt-induced craniosynostosis is one of the late complications of CSF shunting surgery, which affects the patient's condition, clinical picture, and treatment approach. OBJECTIVE: to evaluate the prevalence rate and clinical significance of this disease, define the indications for surgery, and choose the optimal surgical approach. MATERIAL AND METHODS: The study included 59 children with shunt system dysfunction, aged 1 to 14 years, who were treated at the Department in the period from 2014 to 2016. The inclusion criteria were as follows: 1) age at the time of examination is older than 1 year; 2) implantation of a shunt system in the first 12 months of life. The state of cranial sutures was assessed using three-dimensional reconstruction of patient's computerized tomography images. Images obtained before or in the first months after primary implantation of a shunt system were used to exclude cases of primary craniosynostosis. RESULTS: Premature synostosis of the cranial sutures was detected in 27 (46%) cases. Of these, 3 (11%) patients with clinical symptoms of increased intracranial pressure and radiographic signs of craniocerebral disproportion underwent cranial vault remodeling surgery: two biparietal craniotomies and one fronto-parieto-occipital reconstruction. In two cases, simultaneous replacement of a valve with a programmable one was performed. There were no complications after reconstructive surgery. CONCLUSION: Shunt-associated craniosynostosis is one of the late complications of CSF shunting surgery. However, its presence is not an indication for surgery and should not be a reason for surgical aggression. Surgery for increasing the intracranial volume is indicated only for secondary craniosynostosis combined with signs of craniocerebral disproportion. In these cases, reconstructive surgery is an effective treatment option for improving the patient's condition.

Postdiagnostic use of ß-blockers and other antihypertensive drugs and the risk of recurrence and mortality in head and neck cancer patients: an observational study of 10,414 person-years of follow-up.

INTRODUCTION: Growing evidence indicates that norepinephrine promotes cancer growth and metastasis whereas ß-blockers decrease these risks. This study aimed to examine the clinical impact of ß-blockers and other hypertensive drugs on disease recurrence and survival in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study analyzed a cohort of 1274 consecutive patients who received definitive treatments for previously untreated HNSCC at our tertiary referral center between January 2001 and December 2012. Antihypertensive use was considered positive if patients were on medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilized to determine associations between antihypertensive drugs and recurrence, survival, and second primary cancer (SPC) occurrence. RESULTS: Hypertension itself was not a significant variable of recurrence and survival and no antihypertensive drug use affected SPC occurrence (all P > 0.1). After controlling for clinical factors, calcium-channel blocker use remained an independent variable for index cancer recurrence, and ß-blocker use was significantly associated with poor cancer-specific mortality, competing mortality, and all-cause mortality (all P < 0.05). ß-blocker use significantly affected competing and all-cause mortalities in normotensive patients, and calcium-channel blocker use affected index cancer recurrence in normotensive patients (all P < 0.05). CONCLUSIONS: Our data show that ß-blocker use is associated with decreased survival and calcium-channel blockers is associated with increased cancer recurrence in patients of HNSCC.

[The use of frameless navigation during endoscopic interventions in children with multilocular hydrocephalus].

INTRODUCTION: The use of the endoscopic technique largely improves treatment outcomes in patients with multilocular hydrocephalus. However, impaired anatomy and the lack of usual landmarks often cause problems in planning and intraoperative identification of changed structures. The use of frameless navigation during endoscopic interventions can significantly facilitate surgeon tasks and increases the efficacy of surgery. During surgery, the neuronavigation system visualizes a rigid endoscope that interconnects separated ventricles and cysts. Surgery can be completed with guiding a stent through an operating channel of the endoscope and implanting a shunt system. MATERIAL AND METHODS: Ten children underwent 11 endoscopic interventions using frameless intraoperative navigation at our clinic in 2013-2014. The number of surgically interconnected compartments ranged from 3 to 5. Simultaneous placement of a shunt system was performed in 8 of 11 interventions. RESULTS: Clinical improvement as a result of the operation was achieved in all children. 2 patients underwent re-operations 5 months and 1 year after endoscopic intervention. CONCLUSION: Thus, the use of frameless navigation during endoscopic interventions makes their implementation most efficient and safe for the patient.

Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin.

Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells.

Transcriptional regulation of MDR-1 by HOXC6 in multidrug-resistant cells.

Resistance to chemotherapeutic drugs is a significant clinical problem in the treatment of cancer and this resistance has been linked to the cellular expression of multidrug-efflux transporters. The aim of this study was to explore the role of HOXC6 in the regulation of multidrug resistance (MDR) to chemotherapeutic drugs. The HOXC6 gene was identified as being overexpressed in drug-resistant cells compared with parental cell lines. Transfection assays demonstrated that HOXC6 activated MDR-1 promoter activity. A series of MDR-1 promoter deletion mutants was examined and the minimal HOXC6-responsive region was identified to be in the TAAT motif (-2243 bp) of the MDR-1 promoter. Interestingly, overexpression of HOXC6 in the parental cell lines resulted in the upregulation of MDR-1 expression. The inhibition of HOXC6 using small interfering RNA led to the repression of MDR-1. We determined that knockdown of HOXC6 expression in MDR cells increased their sensitivity to paclitaxel. Flow cytometry analysis suggested that siHOXC6 could induce paclitaxel-induced apoptosis and that this was accompanied by an increased accumulation and a decreased release of paclitaxel. Taken together, our findings suggest that HOXC6 expression is an important mechanism of chemotherapeutic drug resistance via its regulation of MDR-1.

AMP-activated protein kinase-α1 as an activating kinase of TGF-ß-activated kinase 1 has a key role in inflammatory signals.

Although previous studies have proposed plausible mechanisms of the activation of transforming growth factor-ß-activated kinase 1 (TAK1) in inflammatory signals, including Toll-like receptors (TLRs), its activating kinase still remains to be unclear. In the present study, we have provided evidences that AMP-activated protein kinase (AMPK)-α1 has a pivotal role for activating TAK1, and thereby regulate NF-κB-dependent gene expressions in inflammatory signaling mediated by TLR4 and TNF-α stimulation. AMPK-α1 specifically interacts with TAK1 and reciprocally regulates their kinase activities. Upon the stimulation of lipopolysaccharide, AMPK-α1-knockdown (AMPK-α1(KD)) or TAK1-knockdown human monocytic THP-1 cells exhibit a dramatic reduction in the TAK1 or AMPK-α1 kinase activity, respectively, and subsequent suppressions of its downstream signaling cascades, which further leads to inhibitions of NF-κB and thereby productions of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. Importantly, the microarray analysis of AMPK-α1(KD) cells revealed a dramatic reduction in the NF-κB-dependent genes induced by TLR4 and TNF-α stimulation, and the observation was in significant correlation with the results of quantitative real-time PCR. Moreover, AMPK-α1(KD) cells are highly sensitive to the TNF-α-induced apoptosis, which is accompanied with dramatic reductions in the NF-κB-dependent and anti-apoptotic genes. As a result, our data demonstrate that AMPK-α1 as an activating kinase of TAK1 has a key role in mediating inflammatory signals triggered by TLR4 and TNF-α.

Strong associations between low-dose organochlorine pesticides and type 2 diabetes in Korea.

Low-dose organochlorine (OC) pesticides have recently been associated with type 2 diabetes in several non-Asian general populations. As there is currently epidemic type 2 diabetes in Asia, we investigated the associations between OC pesticides and type 2 diabetes in Koreans. Among subjects who participated in a community-based health survey, we randomly selected 40 diabetic patients and 40 normal controls. Ten OC pesticides (beta-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, p,p'-DDE, p,p'-DDD, p,p'-DDT, o,p'-DDT, oxychlordane, trans-nonachlor, and mirex) detectable in >or=70% of controls were analyzed in relation to diabetes. Most OC pesticides showed strong associations with type 2 diabetes after adjusting for age, sex, BMI, alcohol consumption, and cigarette smoking. Compared with subjects in the lowest tertile of each OC pesticide, adjusted odds ratios (ORs) in the 3rd tertile ranged from 3.1 (95% CI 0.8-12.1) for heptachlor epoxide to 26.0 (95% CI 1.3-517.4) for oxychlordane. In the case of chemicals belonging to the DDT family, adjusted ORs in the 3rd tertile were in the range of 10.6 (95% CI 1.3-84.9) for p,p'-DDT to 12.7 (95% CI 1.9-83.7) for p,p'-DDE. In this exploratory study with small sample, low-dose background exposure to OC pesticides was strongly associated with prevalent type 2 diabetes in Koreans even though absolute concentrations of OC pesticides were no higher than in other populations. Asians may be more susceptible to adverse effects of OC pesticides than other races.

Curcumin produces an antihyperalgesic effect via antagonism of TRPV1.

Curcumin has diverse therapeutic effects, such as anti-inflammatory, anti-oxidant, anti-cancer, and antimicrobial activities. The vanilloid moiety of curcumin is considered important for activation of the transient receptor potential vanilloid 1 (TRPV1), which plays an important role in nociception. However, very little is known about the effects of curcumin on nociception. In the present study, we investigated whether the anti-nociceptive effects of curcumin are mediated via TRPV1 by using nociceptive behavioral studies and in vitro whole-cell patch-clamp recordings in the trigeminal system. Subcutaneous injection of capsaicin in the vibrissa pad area of rats induced thermal hyperalgesia. Intraperitoneally administered curcumin blocked capsaicin-induced thermal hyperalgesia in a dose-dependent manner. Whereas curcumin reduced capsaicin-induced currents in a dose-dependent manner in both trigeminal ganglion neurons and TRPV1-expressing HEK 293 cells, curcumin did not affect heat-induced TRPV1 currents. Taken together, our results indicate that curcumin blocks capsaicin-induced TRPV1 activation and thereby inhibits TRPV1-mediated pain hypersensitivity.

Metastatic tumours to the jaws and oral soft tissues: a retrospective analysis of 41 Korean patients.

This article describes a pooled analysis of 41 Korean patients with metastatic oral tumours. The data reviewed are from Korean dental and medical case reports published between 1983 and 2004. The mean age was 55.2 years, and the male-to-female ratio was 1.9:1. There were more metastases in the jawbone than in oral soft tissues. The lung was the most common primary site for jawbone metastases, whereas the liver was for those of oral soft tissues. In contrast to reports in Western literature of the breast being the most common primary site, the liver was the most common primary site, followed by the lung and thyroid. These differences may be caused by a relatively high incidence rate of hepatocellular carcinoma in Korea.

Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients.

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Fos-like immunoreactivity in auditory and nonauditory brain structures of hamsters previously exposed to intense sound.

Fos-like immunoreactivity (FLI) was evaluated in auditory and nonauditory brain structures in hamsters that had been exposed previously to intense sound and tested behaviorally for tinnitus. The immunocytochemical results demonstrated a significant increase in exposed animals of FLI in auditory brain structures such as the lateral lemniscus, central nucleus of inferior colliculus, and auditory cortex, as well as in some nonauditory brain structures such as the locus coeruleus, lateral parabrachial nucleus, certain subregions of the hypothalamus, and amygdala. The behavioral scores suggest that animals that had been exposed to intense sound developed tinnitus. This is consistent with the hypothesis that FLI induced by intense sound exposure might represent a neural correlate of tinnitus or of plasticity associated with tinnitus. The possibility and the mechanisms underlying the increased FLI are discussed.

[Mathematical analysis of genetic effects of low doses of ionizing radiation]. / Matematicheskii analiz geneticheskikh éffektov malykh doz ioniziruiushchikh izluchenii.

The comparative study of effects of low doses of radiation on peripheral blood lymphocytes of persons occupationally exposed to radiation and non-exposed ones was carried out. The main attention was paid to radio-adaptive response forming under consistent exposure to low (0.05 Gy) and damaging (2 Gy) doses of gamma-irradiation. Noticeable heterogeneity in capacity for adaptive response forming in occupational group was revealed. The mathematical model adequate to experimental material was constructed using Kohonen neuronets.

Neoceptor concept based on molecular complementarity in GPCRs: a mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides.

Adenosine A(3) receptors are of interest in the treatment of cardiac ischemia, inflammation, and neurodegenerative diseases. In an effort to create a unique receptor mutant that would be activated by tailor-made synthetic ligands, we mutated the human A(3) receptor at the site of a critical His residue in TM7, previously proposed to be involved in ligand recognition through interaction with the ribose moiety. The H272E mutant receptor displayed reduced affinity for most of the uncharged A(3) receptor agonists and antagonists examined. For example, the nonselective agonist 1a was 19-fold less potent at the mutant receptor than at the wild-type receptor. The introduction of an amino group on the ribose moiety of adenosine resulted in either equipotency or enhanced binding affinity at the H272E mutant relative to wild-type A(3) receptors, depending on the position of the amino group. 3'-Amino-3'-deoxyadenosine proved to be 7-fold more potent at the H272E mutant receptor than at the wild-type receptor, while the corresponding 2'- and 5'-amino analogues did not display significantly enhanced affinities. An 3'-amino-N(6)-iodobenzyl analogue showed only a small enhancement at the mutant (K(i) = 320 nM) vs wild-type receptors. The 3'-amino group was intended for a direct electrostatic interaction with the negatively charged ribose-binding region of the mutant receptor, yet molecular modeling did not support this notion. This design approach is an example of engineering the structure of mutant receptors to recognize synthetic ligands for which they are selectively matched on the basis of molecular complementarity between the mutant receptor and the ligand. We have termed such engineered receptors "neoceptors", since the ligand recognition profile of such mutant receptors need not correspond to the profile of the parent, native receptor.

Cell-type specific regulation of thrombospondin-1 expression and its promoter activity by regulatory agents.

Thrombospondin-1 (TSP-1), a multifunctional protein that is able to function as a negative regulator of solid tumor progression and angiogenesis, is normally present at a very low level but rapidly elevated in pathological tissues. To understand the cellular regulation of TSP-1 expression, the mode of it's expression in Hep3B, SK-HEP-1, and porcine aortic endothelial (PAE) cells was examined in the presence of all-trans retinoic acid (ATRA), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or phorbol 12-myristate 13-acetate (PMA). ATRA or IL-6 induced a dose-dependent increase of TSP-1 protein and mRNA levels in PAE cells, while they negatively regulated TSP-1 expression in the Hep3B and SK-HEP-1 cells. In contrast, PMA showed just the opposite effects on the TSP-1 expression in the same cells. IFN-gamma had little effect on TSP-1 level in Hep3B and PAE cells. The TSP-1 expression in SK-HEP-1 cells by these agents showed a close resemblance to that of liver cells rather than that of the endothelial cell line. Possible TSP-1 promoter-mediated responses by ATRA, IL-6, IFN-gamma, or PMA in Hep3B and PAE cells examined with luciferase activity of TSP-LUC reporter plasmid showed that levels of TSP-1 promoter activity were lower than that of the expressed TSP-1 protein and mRNA levels. Transfection of c-Jun and/or RARalpha expression vectors into Hep3B and PAE cells resulted in the enhanced TSP-1 promoter activity as well as the increments of of its protein and mRNA level. These results suggest that regulatory agents-induced TSP-1 expression may be attributed to mRNA stability and/or translational activation in concert with transcriptional activation and TSP-1 expression may be independently controlled via each signal pathway stimulated by PMA or ATRA.