Comparative analysis of buffalo, local and continental cattle carcasses with the European Union classification system in Greece.

The carcasses produced in Greece from Greek Buffalo, indigenous and local crossbred cattle were evaluated using the European Union (EU) bovine classification system and compared with carcasses of continental breeds reared in the country. The main carcass production (67.8%) came from animals born in Greece with a relatively low percentage from local breeds (17%). The lightest carcass weight was found in Greek Brachyceros [145.2 ± 2.3 kg (males); 146.0 ± 3.1 kg (females)], while among locals the Greek Blonde rendered the heaviest carcass weights [303.2 ± 2.9 kg (males); 265.3 ± 3.5 kg (females)]. Muscle conformation scoring was the lowest in Buffalo [4.1 ± 0.1 (males); 4.9 ± 0.0 (females)] and the highest for males of Charolais and Blonde d'Aquitaine (11.2 ± 0.0 and 10.7 ± 0.0, respectively). The meat-purposed breeds produced carcasses of higher quality than dual-purposed, local breeds and dairy Holstein-Friesian. With the discriminant analysis, the correct classification of carcasses varied from 53.4% (males) to 47.8% (females) with high assignment percentage of Greek Buffalo males (81.6%), Simmental males (80.7%) and Holstein-Friesian females (98.5%).

First report of clear cell renal carcinoma metastasizing to the ischiorectal fossa 17 years after radical nephrectomy: an additional reason for lifelong follow-up.

Renal cell carcinoma has a high propensity for metastatic spread. There are several case reports of metastatic renal cell carcinomas associated with rare metastatic sites, in many cases more than ten years after the initial diagnosis. We present a 60-year-old man with perianal pain and a mass in the ischiorectal space, revealed by computed tomography. The patient had a history of clear cell renal carcinoma operated on 17 years ago. A wire localization surgical excision of the ischiorectal fossa mass was performed. The pathological report revealed a metastatic clear cell renal carcinoma. To our knowledge, this is the first case of a clear cell renal carcinoma metastasizing to the ischiorectal fossa reported in the literature. We therefore recommend that any newly discovered mass in any site of a patient with a history of renal cell carcinoma should be carefully explored and biopsied.

Haematocrit and haemoglobin decrease following image-guided percutaneous core needle biopsies.

AIM: To determine the clinical significance of variation in haematocrit (Ht) and haemoglobin (Hb) values before and after image-guided percutaneous core needle biopsies (PCNBs) and evaluate its clinical significance. MATERIALS AND METHODS: This single-centre, retrospective study included all the patients who underwent image-guided PCNBs between November 2012 and September 2018. In total, 105 cases (56 male; 53.3%; mean age 72±8 years) were available for analysis. Biopsies included lesions of the liver, lung, kidney, bone, paravertebral and soft-tissue masses, peritoneal implantations, and retroperitoneal neoplasms. The study's primary outcome was to compare the pre- and post-procedural Ht and Hb values and to evaluate their clinical significance. RESULTS: A significant decrease of the mean Hb and Ht values was detected post-biopsy (12.79±1.85 g/dl versus 12.03±1.72 g/dl and 38.75±4.93% versus 36.49±4.73%; p<0.0001). A decrease in the Ht and/or Hb level was noted in 93/105 (88.6%) and 94/105 (89.5%) of the patients; respectively. Four minor bleeding complications were noted (4/105; 3.8%), which resolved without any further treatment. An >4% decrease in Ht value was noted in 17/105 cases (16.2%) and an Hb decrease of ≥1.5 mg/dl was noted in 10/105 cases (9.5%), all without any haemodynamic compromise. CONCLUSIONS: A moderate post-PCNB decrease in Ht and Hb values compared to baseline should be expected, but should not raise concerns regarding an ongoing bleeding event, if not correlated with haemodynamic and clinical signs of haemorrhage.

Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas.

PURPOSE: MicroRNAs are evolutionarily conserved non-coding components of the transcriptome that can post-transcriptionally control gene expression. Altered microRNA expression has been found to be a common feature of several cancers, including lung carcinomas. The biogenesis and maturation of microRNAs is known to be mediated by the ribonucleases Drosha, Dicer and Ago2. The purpose of the present study was to investigate the expression and distribution of Drosha, Dicer and Ago2 in human non-small cell lung carcinomas (NSCLC) and to relate the respective expression patterns to clinocopatholical features. METHODS: We used five human NSCLC-derived cell lines and primary formalin-fixed paraffin-embedded tissue samples from 83 NSCLC patients. Drosha, Dicer and Ago2 mRNA and protein expression levels, and their sub-cellular distributions, were assessed using RT-PCR, Western blotting, immunofluorescence and immunohistochemistry, respectively. RESULTS: We found that Drosha, Dicer and Ago2 were expressed in all the cell lines and primary neoplastic and non-neoplastic tissue samples tested. The intensity of the immunohistochemical staining was found to be significantly lower in stage I tumors compared to normal lung tissues. Dicer expression was found to be significantly higher in stage II compared to stage I tumors, and in stage III compared to stage II and stage I tumors. CONCLUSIONS: Our results point at a role of Drosha, Dicer and Ago2 in the development of NSCLC and suggest that Dicer may be implicated in the progression of these tumors to advanced stages.

The inhibition of aromatase alters the mechanical and rheological properties of non-small-cell lung cancer cell lines affecting cell migration.

Tumor invasion and metastasis are key aspects of non-small cell lung cancer (NSCLC). During migration, cells undergo mechanical alterations. The mechanical phenotype of breast cancer cells is correlated with aromatase gene expression. We have previously shown that targeting aromatase is a promising strategy for NSCLC. The aim of this study was to examine morphological and mechanical changes of NSCLC cells, upon treatment with aromatase inhibitor and correlate their ability to migrate and invade. In vitro experiments were performed using H23 and A549 NSCLC cell lines and exemestane was used for aromatase inhibition. We demonstrated that exemestane reduced H23 cell migration and invasion and caused changes in cell morphology including increased vacuolar structures and greater pleomorphism. In addition, exemestane changed the distribution of α-tubulin in H23 and A549 cells in a way that might destabilize microtubules polymerization. These effects were associated with increased cell viscosity and decreased elastic shear modulus. Although exemestane caused similar effects in A549 cells regarding viscosity and elastic shear modulus, it did not affect A549 cell migration and caused an increase in invasion. The increased invasion was in line with vimentin perinuclear localization. Our data show that the treatment of NSCLC cells with an aromatase inhibitor not only affects cell migration and invasion but also alters the mechanical properties of the cells. It suggests that the different origin of cancer cells is associated with different morphological characteristics and mechanical behavior.

Body fat distribution by anthropometric and MRI-based techniques in relation to insulin secretion and action in men with diabetes.

AIM: Differences in fat accumulation and distribution might be responsible for the greater insulin resistance (IR) in type 2 diabetes. The study aims at examining the relationship between fat accumulation and distribution, and insulin secretion and action, by multilevel methodological approach. METHODS: Thirty-three diabetic men (D), and 28 sex, age and BMI-matched controls (C) were studied for glucose and insulin during OGTT, insulin resistance and sensitivity, employing HOMA and Matsuda index respectively, and, fat accumulation and distribution by anthropometrics, Bioimpendance Analysis (BIA), and multiple slices MRI of abdomen and hip. RESULTS: D exhibited higher HOMA compared to C (P<0.001), and lower Matsuda index (P=0.062). No differences in fat distribution by anthropometric or MRI measurements were observed; however, fat accumulation by BIA was higher in D (P=0.035). HOMA correlated to basal, AUC, and peak insulin in both groups (all P<0.001); with weight (r=0.415, P=0.031), hip circumference (HC) (r=0.482, P=0.011), %fat (r=0.400, P<0.05) in C; and with weight, BMI, total and %fat, and waist and HC when all subjects were considered as a group. Matsuda inversely correlated with basal, AUC, and peak insulin (all P<0.001), and HC (r=-0.406, P=0.032) in C. HOMA strongest correlated with L3-L4 subcutaneous (r=0.551, P=0.003) in C, and with L3-L4 visceral (r=0.456, P=0.022) in D. CONCLUSION: The greater IR in diabetic patients may not be interpreted by differences in fat distribution. IR correlates with different fat compartments in healthy and diabetic subjects of comparable fat distribution, suggesting differences in fat function.

Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.

Members of the ADAMTS family of proteases degrade proteoglycans and thereby have the potential to alter tissue architecture and regulate cellular functions. Aggrecanases are the main enzymes responsible for aggrecan degradation, due to their specific cleavage pattern. In this study, the expression status, the macromolecular organization and localization of ADAMTS-1, ADAMTS-4/aggrecanase-1 and ADAMTS-5/aggrecanase-2 in human normal larynx and laryngeal squamous cell carcinoma (LSCC) were investigated. On mRNA level, the results showed that ADAMTS-4 was the highest expressed enzyme in normal larynx, whereas ADAMTS-5 was the main aggrecanase in LSCC presenting a stage-related increase up to stage III (8-fold higher expression compared to normal), and thereafter decreased in stage IV. Accordingly, immunohistochemical analysis showed that ADAMTS-5, but not ADAMTS-4, was highly expressed by carcinoma cells. Sequential extraction revealed an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes within the cancerous and their corresponding macroscopically normal laryngeal tissues, compared to the normal ones. Importantly, these analyses indicated that critical macromolecular changes occurred from the earliest LSCC stages not only in malignant parts of the tissue but also in areas that were not in proximity to carcinoma cells and appeared otherwise normal. Overall, the results of the present study show that ADAMTS-5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma suggesting a critical role for the enzyme in aggrecan degradation and laryngeal tissue destruction during tumor progression.

Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet.

OBJECTIVE: Recent data suggest that obesity and related metabolic aberrations are associated with osteoarthritis (OA) development, a phenomenon that is attributed at least in part to the consumption of lipid-rich diets. To date, the molecular mechanisms that govern the lipid-OA connection remain largely unknown. Given the important role of high-density lipoprotein (HDL) in plasma and tissue lipid metabolism, the main purpose of the present study was to investigate the role of HDL metabolism in the pathobiology of OA. METHODS: We used apolipoprotein A-I (apoA-I)(-/-) mice that lack classical apoA-I containing HDL, LCAT(-/-) mice that have only immature HDL and relatively reduced HDL-cholesterol levels and control C57BL/6 mice. Mice were placed on chow or western-type (WTD) and monitored for 24 weeks. Knee joints were removed and articular cartilage was isolated for further analyses. RESULTS: The LCAT(-/-) mice were significantly more sensitive to the development of diet-induced obesity compared to the C57BL/6 and apoA-I(-/-) mice. Morphological, biochemical and molecular analyses revealed that the LCAT(-/-) obese mice developed OA, while the C57BL/6 mice that were fed WTD did not. Notably, apoA-I(-/-) mice that received WTD also developed OA although their body-weight gain was similar to their wild-type counterparts. Interestingly, bone marrow from LCAT(-/-) and apoA-I(-/-) mice contained significantly increased number of adipocytes, compared to the other groups. CONCLUSIONS: Our findings suggest that perturbations in HDL metabolism predispose to OA following chronic insult with WTD and raise the challenging possibility that HDL has a causative relation to OA in patients with metabolic syndrome.

New experimental rabbit animal model for cervical spondylotic myelopathy.

STUDY DESIGN: Cervical spondylotic myelopathy (CSM) represents the most commonly acquired cause of spinal cord dysfunction among individuals over 55 years old. The pathophysiology of the disease involves static and dynamic mechanical factors, which are the result of chronic degeneration. The clinical course of the disease remains unpredictable. In the past, many experimental animal models have been developed to study the cellular and molecular mechanisms underlining the pathophysiology of the disease. OBJECTIVES: To create a new animal model of CSM, which will reproduce the temporal course of the disease and the local microenvironment at the site of spinal cord compression. METHODS: We performed posterior laminectomy to New Zealand rabbits at the level of C7, and a thin sheet (5-7 µm) of aromatic polyether was implanted with microsurgical technique at the epidural space underneath C5-C6 laminae. Motor function evaluation was performed after the operation and once a week thereafter. RESULTS: After 20 weeks, the animals were killed, and the histological evaluation of spinal cord at the site of compression above and below it, using eosin hematoxylin, immonohistochemistry and Kluver-Barrera techniques reveals axonal swelling and demyelination, interstitial edema and myelin sheet fragmentation. Moreover, histological evaluation of C5 and C6 laminae reveals osteophyte formation. CONCLUSION: We believe that this CSM model reproduces the temporal evolution of the disease and creates a local microenvironment at the site of spinal cord compression, which shares the same characteristics with that of human disease.

The effect of different physical activity levels on muscle fiber size and type distribution of lumbar multifidus. A biopsy study on low back pain patient groups and healthy control subjects.

AIM: Previous studies examining the multifidus fiber characteristics among low back pain (LBP) patients have not considered the variable of physical activity. The present study sought to investigate the muscle fiber size and type distribution of the lumbar multifidus muscle among LBP patient groups with different physical activity levels and healthy controls. METHODS: Sixty-four patients were assigned to one of three groups named according to the physical activity level, determined for each patient by the International Physical Activity Questionnaire. These were low (LPA), medium (MPA) and high (HPA) physical activity groups. A control group comprising of 17 healthy individuals was also recruited. Muscle biopsy samples were obtained from the multifidus muscle at the level L4-L5. RESULTS: contrast with the control group, LBP patient groups showed a significantly higher Type II fiber distribution as well as reduced diameter in both fiber types (P<0.05). The physical activity level did not have an effect on multifidus characteristics since no significant differences were observed in fiber type and diameter (P>0.05) among LPA, MPA and HPA patient groups. Various pathological conditions were detected which were more pronounced in LBP groups compared to the control (P<0.05). Males had a larger fiber diameter compared to females for both fiber types (P<0.05). CONCLUSIONS: The results showed that the level of physical activity did not affect muscle fiber size and type distribution among LBP patients groups. These findings suggest that not only inactivity but also high physical activity levels can have an adverse effect on the multifidus muscle fiber characteristics.

Increased cytoplasmic level of migfilin is associated with higher grades of human leiomyosarcoma.

AIMS: Leiomyosarcomas (LMS) are malignant neoplasms composed of cells that exhibit distinct smooth muscle differentiation. The molecular and cytogenetic features of LMS are complex and no consistent aberrations have been reported to date. Mitogen inducible gene-2 (Mig-2), kindlin and migfilin are recently identified cell-matrix adhesion proteins. The aim was to determine the expression and distribution of these proteins in human smooth muscle tumours of somatic soft tissue. METHODS AND RESULTS: Immunohistochemistry was performed on a human LMS tissue microarray and on sections of human leiomyomas (LM) and normal smooth muscle. Migfilin was barely detectable in normal smooth muscle cells, whereas increased levels of migfilin were observed in the majority of LM and LMS. Furthermore, the cytoplasmic level of migfilin was strongly associated with higher tumour grades. Additionally, the cytoplasmic levels of migfilin and Mig-2 were correlated with each other, suggesting an association between the two in the cytoplasm. Kindlin was expressed in normal smooth muscle, LM and LMS, and its level did not correlate with tumour grade. CONCLUSIONS: Our results suggest a role for cytoplasmic migfilin in the progression of LMS and identify cytoplasmic migfilin as a potentially important biological marker for human LMS progression.

Angiogenic effect of intramuscular administration of basic and acidic fibroblast growth factor on skeletal muscles and influence of exercise on muscle angiogenesis.

BACKGROUND: Angiogenic factors which control the angiogenic process represent a promising strategy for restoration of blood flow, but require further evaluation before clinical use. Exercise has also been reported to induce neovascularisation in muscles. OBJECTIVES: To evaluate the angiogenic effects of basic fibroblast growth factor (b-FGF) and acidic fibroblast growth factor (a-FGF) on rat gastrocnemius muscle, when administered intramuscularly, and to compare them with those obtained by daily exercise. METHODS: Forty nine rats were allotted to the following groups: A, controls; B, exercise by swimming; C1 and C2, intramuscular injection of b-FGF and a-FGF respectively; D1 and D2, b-FGF and a-FGF injection in combination with exercise. The antibody mouse anti-rat CD31 was used to evaluate the numbers of blood vessels present in histological preparations of gastrocnemius muscle. RESULTS: Significant increases in the numbers of blood vessels of the right gastrocnemius muscles in groups C1 and D1 were observed compared with controls (p<0.05). There was only a slight increase in angiogenesis in the left gastrocnemius muscle of groups C1 and D1 compared with controls (p>0.05), and there was a decrease in angiogenesis in the gastrocnemius muscle of the swimming group compared with controls. CONCLUSION: The intramuscular administration of b-FGF, but not a-FGF, induced significant local angiogenesis in gastrocnemius muscle at the site of injection.

The MAPK-AP-1/-Runx2 signalling axes are implicated in chondrosarcoma pathobiology either independently or via up-regulation of VEGF.

AIMS: To investigate whether and how the JNK/ERK-AP-1/-Runx2 signalling pathways and vascular endothelial growth factor (VEGF) are engaged in the pathogenesis of cartilaginous tumours. Chondrosarcoma is the third most common primary skeletal malignancy. Nevertheless, the molecular events underlying its pathogenesis remain elusive. JNK/ERK MAPKs and their downstream effectors, c-Jun and c-Fos (AP-1), are involved in chondroblastic differention/proliferation. These proteins interact with the Runx2 transcription factor, which is also implicated in chondroblast biology. VEGF, a key angiogenic factor, is up-regulated in human chondrosarcomas. METHODS AND RESULTS: Normal cartilage and neoplastic cells from 45 chondrosarcomas and 21 enchondromas were investigated immunohistochemically. We evaluated the cellular levels of JNK2, p-JNK2 (phosphorylated/activated JNK2), its main substrate, c-Jun, pc-Jun (phosphorylated/activated c-Jun) and c-Fos. Moreover, the levels of p-ERK (phosphorylated/activated ERK), Runx2 and VEGF were assessed. Positive immunostaining for all proteins was observed in the majority of the examined chondrosarcomas and in a small fraction of enchondromas. The expression levels of all proteins were positively and significantly correlated with each other. These levels were substantially augmented in high-grade compared with low-grade chondrosarcomas and in low-grade tumours compared with benign enchondromas, implying a potential use as molecular markers for prediction of high-grade neoplasms. CONCLUSIONS: The JNK/ERK-AP-1/-Runx2 signal transduction 'network' is associated with chondroblastic malignant transformation and chondrosarcoma development, either separately or through coordinated induction of VEGF.

Multiple brown tumors of the ribs simulating malignancy.

Bone disease associated with primary hyperparathyroidism, known as osteitis fibrosa cystica, is now very rarely encountered, since the parathyroid disorder is most often diagnosed at the early stage of asymptomatic hypercalcemia. Here, we report the case of a patient with multiple pleural-based masses and hypercalcemia, which led to the presumptive diagnosis of malignancy. However, histological and laboratory data were consistent with the development of brown tumors of the ribs due to underlying severe hyperparathyroidism.

Multimodality treatment of neuroendocrine tumors of the thymus.

BACKGROUND: Neuroendocrine tumors of the thymus are rare neoplasms. Four patients with this tumor who underwent multimodality treatment are presented and the literature is briefly reviewed. METHODS: The medical records of all patients treated for neuroendocrine tumors of the thymus from 1979 to 2002 were reviewed. Tumors were classified using a slight modification of the World Health Organization criteria. RESULTS: The patients' median age was 38 years. All patients underwent extensive excision of the tumor. Histological diagnosis was atypical carcinoid (2), typical carcinoid (1), and small cell carcinoma (1). All patients developed recurrence(s). One patient died 132 months after diagnosis. The remaining three patients are alive with no symptoms at 135, 99, and 35 months, respectively, after diagnosis. Two patients with recurrences have been on treatment with Octreotide LAR with satisfactory results. One patient is free of disease. CONCLUSIONS: Neuroendocrine tumors of the thymus are potentially aggressive tumors. Radical resection is the treatment of choice. The encouraging results obtained by administration of Octreotide LAR in two of our patients warrant further investigation.

Follicular fluid levels of vascular endothelial growth factor and leptin are associated with pregnancy outcome of normal women participating in intracytoplasmic sperm injection cycles.

Cytokines play a critical and multifarious role in follicular maturation. Consequently, they may influence the pregnancy outcome in cycles of assisted reproduction. The aim of this study was to measure the levels of tumor necrosis factor-alpha (TNFalpha), vascular endothelial growth factor (VEGF) and leptin in serum and follicular fluids (FFs) from women undergoing controlled ovarian hyperstimulation (COH) for intracytoplasmic sperm injection cycles (ICSI). We tried to investigate their interrelationships and to evaluate them as predictive markers for the cycle's outcome. Seventeen women participated in this study. Male factor infertility was the only indication for ICSI cycles. For COH, the long agonist protocol with triptorelin and recombinant FSH was employed. Cytokines levels were evaluated by ELISA. Serum cytokine levels did not differ between pregnant and non-pregnant women. FF-VEGF levels were significantly elevated in non-pregnant women (722.2+/-1093.2 pg/ml) as compared to pregnant women (290.3+/-259.8 pg/ml). Leptin concentrations were also significantly higher in FFs of non-pregnant women (682.6+/-625.1 ng/ml) than those of pregnant women (231.6+/-286.5 ng/ml). There were significant positive correlations between FF-leptin and age, as well as between FF-leptin and FF-VEGF concentrations. It was concluded that elevated FF-leptin and VEGF levels are associated with failure of conception in IVF cycles and may serve as markers in clinical practice.

Aggressive angiomyxoma of the vagina: a case report and review of the literature.

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor of the lower pelvis and genital region, characterized by local infiltration and frequent, even multiple recurrences. In the present paper a case of a small-sized AA of the vagina, in a 55-year-old woman is reported. We describe the histological appearance and the immunohistochemical phenotype of this tumor and discuss its differential diagnosis from other mesenchymal lesions occurring in the pelvic and genital region. Furthermore, we attempt to enlighten the possible mechanisms that govern the pathogenesis and the biological behavior of this "mysterious" neoplasm.

Loop colostomy without a rod.

Loop colostomy is traditionally prevented from retracting into the peritoneal cavity by a rod or other supporting device. The rod can be safely replaced by a single suture. The technique facilitates fitting of the ostomy bag and eliminates the need to remove the supporting element later on.

Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas.

Osteosarcomas represent the most common primary malignant bone tumors; however, comprehension of the molecular mechanisms underlying their pathogenesis is far from thorough. Studies in cultured cells have demonstrated that the c-Jun N-terminal kinase (JNK) signal transduction pathway participates in the proliferation, differentiation, and apoptosis of osteoblasts. Phosphorylated JNKs activate the oncoprotein c-Jun, which is known to form the activator protein-1 (AP-1) transcription factor as a homo- or heterodimer. c-Jun's principal dimerization partner is c-Fos, which participates in the differentiation and function of osteoblasts and in the pathogenesis of osteosarcomas. A similar role for the JNK cascade in the malignant transformation of human osteoblasts and in the generation of osteosarcomas has not been documented. Our study addressed the possibility that a functional upregulation of the JNK pathway is implicated in the pathogenesis of osteosarcomas. To this end, we employed immunohistochemistry to examine normal bone and osteosarcoma cells in paraffin-embedded sections from 56 patients with high-grade tumors and 15 patients with low-grade tumors. We assessed the protein levels of the two major JNK isoforms (JNK1 and JNK2); their phosphorylated-hence activated-species, p-JNK; their substrate, c- Jun; its phosphorylated (activated) form, pc-Jun; and c-Jun's heterodimeric partner, c-Fos. We also examined the immunohistochemical profile of the alpha chain of the nascent polypeptide-associated complex (alpha-NAC), an osteoblast-specific AP-1 coactivator that potentiates the transcriptional activity of the c-Jun/c-Jun homodimer. Positive immunostaining for JNK1, JNK2, p-JNK, c-Jun, pc-Jun, c-Fos, and alpha-NAC was observed in 86, 93, 94, 99, 97, 99, and 97.5% of the samples, respectively, whereas normal bone was devoid of these immunoreactivities. The cellular levels of all proteins were significantly correlated to each other (P < 0.001 for each correlation). Moreover, significantly higher expression levels of all proteins were detected in high-grade tumors compared to levels in low-grade ones. The observed expression profile of alpha-NAC implies that the active AP-1 in human osteosarcomas most likely comprises c-Jun/c-Jun homodimers. When cellular levels of the JNK pathway components and c-Fos were evaluated as possible biological markers of tumor grade, high expression of c-Jun and abundant pc-Jun predicted a high-grade tumor. Our findings provide novel evidence that the JNK signaling pathway is functionally operative in the malignant transformation of osteoblasts and the subsequent development and progression of human osteosarcomas. Evaluation of c-Jun expression and JNK-dependent activation may facilitate an improved prediction of the tumor's clinical behavior and potentially be exploited in designing patient-tailored treatment regimens.

Differential stimulation of somatostatin but not neuropeptide Y gene expression by quinolinic acid in cultured cortical neurons.

Somatostatin (SS) and neuropeptide Y (NPY) are coproduced in a subpopulation of neurons that are selectively resistant to NMDA neurotoxicity. We have previously reported that quinolinic acid (QUIN), an NMDA receptor agonist, augments SS mRNA in cultured fetal rat cortical neurons. This study examines coregulation of SS and NPY by QUIN and NMDA in cultured cortical neurons and compares the effects of these agents with those of forskolin and phorbol 12-myristate 13-acetate (PMA), known to activate SS and NPY gene transcription by protein kinase A- and protein kinase C-dependent mechanisms. In addition, transcriptional regulation of the SS gene was investigated by acute transfection of cortical cultures with an SS promoter-chloramphenicol acetyltransferase (CAT) construct. QUIN and NMDA displayed dose-dependent fourfold augmentation of levels of mRNA for SS but not for NPY. In contrast, forskolin and PMA increased both SS and NPY mRNA levels. QUIN- and NMDA-mediated induction of SS mRNA was blocked by the NMDA receptor antagonist (-)-2-amino-5-phosphonovaleric acid and displayed regional brain specificity because it was not observed in fetal hypothalamic cell cultures. In time course studies, the effects of QUIN/NMDA on SS mRNA occurred after a latency of 8 h, indicating a delayed effect. Cortical cells transfected with pSS-750 CAT showed three- to fourfold stimulation of CAT activity with forskolin but not by QUIN or NMDA. These data reveal a dose-dependent, tissue-specific, NMDA receptor-mediated stimulation of SS but not NPY mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)