The source of urinary epidermal growth factor in humans

Summary To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118±12 vs 105±6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5±0.25 vs 1.5±0.18 ng/ml in males and females respectivelyp<0.05). Urine EGF excretion averaged 1641±233 ng/h in males and 1507±191 ng/h in females (p>0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98,p<0.01) and female (r=0.94,p< 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 g/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.Abbreviations EGF epidermal growth factor - hEGF human epidermal growth factor - IGF insulin-like growth factor - TGF alpha transforming growth factor - TGF beta transforming growth factor - NGF nerve growth factor - PDGF platelet derived growth factor - CPDA citrate phosphate dextrose adenine buffer - EDTA ethylenedinitrilotetraacetic acid - PBS phosphate saline buffer     

Serum interleukin-23 protects,whereas methotrexate treatment stimulates selected components of the metabolic syndrome in patients with SAPHO syndrome

IntroductionThe aim of the study was to evaluate the impact of disease activity, selected serum cytokines, and therapy on metabolic syndrome (MetS) components in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.Material and methodsWe studied 46 SAPHO patients (40 women, 6 men). We recorded age, sex, disease duration, arthritis localization, type of skin changes, bone scintigraphy results, comorbidities, BASDAI, VAS, and treatment. We measured erythrocyte sedimentation rate, C-reactive protein, lipid profile, serum IL-6, IL-18, IL-23, endothelin-1, vascular endothelial growth factor, and epidermal growth factor (EGF).Results97.8% of patients had sternoclavicular joint arthritis, 91.3% of patients palmoplantar pustulosis. In 65.2% of SAPHO patients skin changes and arthritis started simultaneously. Apart from non-steroidal anti-inflammatory drugs, patients were treated with methotrexate (41.3%), sulfasalazine (41.3%), and antibiotics (39.1%). 19.5% of patients met MetS criteria. Serum IL-23 correlated positively with total cholesterol (TC; p = 0.02) and high-density lipoprotein cholesterol (HDL-C) (p = 0.01) in the SAPHO group. There was a negative correlation between HDL-C and BASDAI (p = 0.02). Patients treated with methotrexate had higher triglyceride (p = 0.01) and low-density lipoprotein cholesterol (LDL-C) (p = 0.01) levels. There was a negative correlation between TC and EGF (p = 0.03). Increased prevalence of autoimmune diseases and depression was observed in SAPHO patients.ConclusionsSerum IL-23 protects, whereas methotrexate treatment stimulates selected components of the MetS in patients with SAPHO syndrome.     

Effects of EGF and TGFβ1 on c‐myc gene expression and DNA synthesis in embryonic hamster palate mesenchymal cells

Previous work has shown that cell proliferation is a major contributor to the early palate morphogenesis in mammals. The present study was undertaken to examine the effect of EGF, TGFβ₁ and their combination on proliferation (measured by DNA synthesis) and on the expression of a growth related proto‐oncogene, c‐myc, in embryonic hamster palate mesenchymal cells (HPMC). Vertically developing hamster palatal shelves were dissected on day 11 of gestation, and trypsinized, and primary cultures were grown in DMEM + 10% serum at 37°C and 5% CO₂. Following appropriate growth factor treatment of HPMC, DNA synthesis was measured by scintillation counting and extracted RNA was subjected to Northern blot analysis. In serum‐starved, pre‐confuent cultures treated with EGF (20 ng/ml), DNA synthesis was stimulated in the presence of 2.5% serum. In contrast, treatment of HPMC with TGFβ₁ (10 ng/ml) in the presence or absence of EGF/serum for 24 hr, or HPMC pre‐treatment with TGFβ₁ (30 min) followed by EGF/serum (24 hr), resulted in an arrest of DNA synthesis. Northern blot analysis of RNA extracted from HPMC showed that as serum‐starved, growth‐arrested cells progressed through G0 to G1 phase of the cell cycle, following EGF treatment, c‐myc was expressed by 1 hr and declined thereafter. In contrast, TGFβ₁ did not support expression of c‐myc. Following pre‐ or co‐treatment with TGFβ₁, the EGF ± serum‐induced expression of c‐myc was seen between 1 and 6 hr. It appears that EGF‐induced expression of c‐myc may be involved in advancing the HPMC in G1, and thus may contribute to the onset of DNA synthesis in HPMC. Since co‐ or pre‐treatment with TGFβ₁ did not inhibit EGF/serum induced expression of c‐myc, it is possible that growth arresting effect of TGFβ₁ may not be exerted directly through inhibition or blockage of c‐myc expression. Anat Rec 254:453–464, 1999. © 1999 Wiley‐Liss, Inc.     

Epidermal Growth Factor Behaves as a Partial Agonist in Hepatocytes: Effects on DNA Synthesis in Primary Culture and Competition with Transforming Growth Factor α

Abstract

The structurally related mitogens epidermal growth factor (EGF) and transforming growth factor a (TGFα) are believed to exert all their effects via the same receptor. We have compared the effects of EGF and TGFα, and examined their interaction, on DNA synthesis in cultured rat hepatocytes. The potency of the two agents was similar, or slightly higher for EGF, but TGFα stimulated the DNA synthesis more efficiently, producing at high levels a rate of S phase entry that clearly exceeded (two to threefold) that obtained with maximally effective concentrations of EGF. While the hepatocytes became more sensitive both to TGFα and EGF when addition of the agents was postponed until late in the prereplicative period, TGFα exhibited higher efficacy than EGF both at early and late exposure. When EGF and TGFα were added together at 24 h, TGFα further enhanced the DNA synthesis in the presence of a saturating concentration (5 nM) of EGF, while EGF dose-dependently reduced the DNA synthesis in the presence of a high concentration (10 nM) of TGFα. The results show a lower efficacy of EGF than of TGFα, and, therefore, EGF displays the characteristics of a partial agonist in its EGF receptor-mediated growth stimulation in hepatocytes.     

Separation of transforming growth factors TGF alpha and TGF beta during chromatographic purification of extracts from mouse C-234 tumors

Polypeptide transforming growth factors: TGF alpha and TGF beta were isolated and separated from acidic ethanol extracts of mouse C-243 tumors. The purification of the acid-soluble extract was achieved by Bio-Gel P-60 filtration chromatography, followed by CM-Sepharose CL-6B ion exchange, Bio-Gel P-10 filtration, and dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At the Bio-Gel P-10 purification step, TGF alpha was separated from TGF beta. TGF alpha stimulated mouse Balb/c-3T3, rat NRK-49F and human A549 cells to form colonies in soft agar, and competed with 125I-labeled epidermal growth factor (EGF) for binding to human placenta membrane receptors. Over 40,000-fold SDS-PAGE-purified TGF beta had an Mr of 25,000. Unlike TGF alpha, TGF beta stimulated the clonal growth of NRK fibroblasts only in the presence of the suboptimal amounts of EGF (0.5 ng/ml). TGF beta significantly inhibited the anchorage-independent growth of malignant human lung carcinoma A549 cells, and in the radioreceptor assay with 125I-EGF it had no affinity to EGF receptors.     

Spontaneously Transformed NRK Cells Lose Their Mitogenic Response to Epidermal Growth Factor

Abstract

To understand the relationship between growth factor-induced mitogenesis and spontaneous cell transformation, a clonal isolate of epidermal growth factor (EGF)-responsive NRK cells was passed in vitro until morphologically transformed variants arose. Subclones of EGF responsive (Cl-3) and EGF nonresponsive (Cl-10) NRK cells were isolated. Cl-3 cells grew as flat, contact-inhibited monolayers, while Cl-10 cells grew as rounded or spindle-shaped cells that formed dense foci. Cl-10 cells formed colonies in soft agar more efficiently (p < 0.01) and formed larger tumors in nude mice (p < 0.05) than Cl-3 cells. Cl-3 cells exhibited a sixfold increase in DNA synthesis in response to 1.0 uM EGF. Cl-10 cells did not increase DNA synthesis on exposure to 100 uM EGF. These different responses to EGF occurred despite similar numbers of receptors and similar receptor binding affinities for EGF (Cl-3: 7000 receptors, K_d=0.67 nM; Cl-10: 8000 receptors, K_d=0.72 nM). No evidence of transforming growth factor-alpha was detected in either of these cell lines using Northern blots, Western blots, or biologic assays. We conclude that NRK cells which undergo spontaneous morphologic transformation and exhibit enhanced anchorage-independent growth lose their mitogenic response to EGF.     

The effect of epidermal growth factor on production of vascular endothelial growth factor by amnion-derived (WISH) cells

Our objective was to clarify the physiological role of vascular endothelial growth factor (VEGF) by amnion-derived (WISH) cells. WISH cells were cultured, and the effect of epidermal growth factor (EGF), mitogen-activated protein (MAP) kinase kinase or extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors (U0126) or phosphatidylinositol (PI) 3-kinase on the production of VEGF was examined. VEGF was assayed by ELISA. The activation of MAP kinase and akt, which is phosphorylated by PI 3-kinase, were detected by Western blot analysis using anti-phosphorylated MAP kinase antibody and anti-phosphorylated akt antibody. In the time course of VEGF production following EGF treatment, VEGF production showed a significant increase only after 16 (p < 0.01)–32?h (p < 0.01). EGF increased the production of VEGF by WISH cells in a dose-dependent manner. The MAP kinase and akt activity were determined by treatment with EGF. VEGF production was significantly decreased following pretreatment with U0126 or wortmannin for two hours before treatment with EGF (p < 0.01, p < 0.01). WISH cells appeared to produce VEGF via a mechanism involving tyrosine kinase activation of EGF receptor and MAP kinase or PI 3-kinase. It is suggested that VEGF may contribute to the neovascularization and proliferation of the placenta and gestational tissue, and EGF may play an important role in regulation of VEGF production in the placenta.     

Immunocytochemical expression of growth factors by odontogenic jaw cysts.

AIM: To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst. METHODS: Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12). RESULTS: The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type. CONCLUSIONS: These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis.     

Modulation of Hen Granulosa Cell Steroidogenesis and Plasminogen Activator Activity by Transforming Growth Factor Alpha

Abstract

Studies were conducted with chicken granulosa cells to evaluate the relative efficacy of human recombinant transforming growth factor alpha (TGFα) versus murine epidermal growth factor (EGF) to affect cyclic adenosine monophosphate (cAMP) accumulation and progesterone production stimulated by luteinizing hormone (LH) or steroid output induced by a cAMP analogue, and to modulate plasminogen activator (PA) activity.

Increasing concentrations of EGF (33–328 nM) and TGFα (0.04–18'nM) were found to inhibit cAMP formation stimulated by LH in a dose-dependent manner, with calculated half-maximal inhibitory doses (ID₃₀s) of 97.1 and 0.27 nM, respectively. Similarly, a 470-fold difference in the ability of TGFa (ID₃₀ = 0.13 nM) versus EGF (ID₃₀ = 61.3 nM) to half-maximally suppress LH-induced progesterone production was observed in the same cells. Progesterone production stimulated by a cAMP analogue (8-bromo-cAMP, 1 mM) was also attenuated by EGF (ID₃₀ = 75.9 nM) and TGFa (ID₃₀ = 0.08 nM), suggesting a post-cAMP site of inhibition by these growth factors on steroidogenesis. Finally, a 260-fold to 330-fold difference in the efficacy of TGFα versus EGF to half-maximally stimulate cell-associated and secreted PA activity was observed.

From these data, we propose that TGFα may serve an important role in regulating follicular growth and maturation in the domestic hen via its ability to affect granulosa cell steroidogenesis and plasminogen activator activity.     

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PurposeA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E₂ (PGE₂), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL).Material/methodsSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario.ResultsSalivary pH in BE was significantly lower than in controls during mechanical (p < 0.001) and chemical stimulations (p < 0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p < 0.05) and chemical stimulations (p < 0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p < 0.05) and during mechanical (p < 0.05) and chemical stimulations (p < 0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p < 0.05). We observed a higher TGFα output during mastication (p < 0.05) and PGE₂ secretion during basal and masticatory condition (p < 0.05) in BE.ConclusionsPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.     

Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers.

Growth factors secreted by platelets and macrophages may play roles in atherogenesis and in wound repair. The multiple biologic effects of these factors are being studied extensively in vitro, but their roles in vivo are relatively unexplored. The cellular responses to platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) were examined in a wound chamber model in rats. Growth factors were emulsified in bovine dermal collagen suspensions, placed in 1 X 30-mm porous polytetrafluoroethylene tubes, inserted subcutaneously, and removed after 10 days. The presence of PDGF (400 ng), TGF beta (200 ng), or bFGF (100 ng) increased the DNA content of the chambers two- to sixfold, compared with controls. Regardless of dose, EGF (100-800 ng) did not affect the DNA content. The increases in DNA observed for PDGF, TGF beta, or bFGF resulted from accumulations of varying numbers of fibroblasts, capillaries, macrophages, and leukocytes in 10-day chambers. The addition of 250 micrograms/ml heparin to the collagen suspension potentiated the response to PDGF and bFGF, but not to TGF beta or EGF. The clearance of 125I-labeled growth factors from the chambers was biphasic. After an initial rapid phase, the remaining growth factor was slowly cleared. The half-life of the initial phase was rapid for PDGF (12 hours) and bFGF (9 hours) and somewhat slower for TGF beta (22 hours). There was no difference in the rate of clearance between collagen and collagen/heparin matrices for any of the growth factors examined. These studies demonstrate that PDGF, bFGF, and TGF beta can induce granulation tissue development in normal animals. The similarity in cellular responses to three peptides with differing in vitro actions suggests that the responses observed at 10 days reflect a secondary process, possibly mediated by effector cells such as macrophages, lymphocytes, or granulocytes that are attracted into the chamber by each growth factor, rather than a direct effect of the factors themselves.     

Invasion and EMT-associated genes are up-regulated in B viral hepatocellular carcinoma with high expression of CD133-human and cell culture study

Hepatocellular carcinomas (HCCs) with expression of stem/progenitor cell markers including CD133 have been reported to have more aggressive biological behavior, and epithelial–mesenchymal transition (EMT), closely related invasion, has been suggested to generate cancer stem cells. To elucidate biological characteristics of HCCs expressing CD133, we evaluated migration assay and the mRNA expression levels of CD133, invasion-associated genes [urokinase plasminogen activator receptor (uPAR), villin 2 (VIL2), and MMP1 and MMP2], and EMT regulators (Snail, Slug, Twist, E-cadherin, and N-cadherin) by real-time PCR in HCC cell lines including HepG2, Hep3B, Huh7, PLC/RFP/6, SNU423, SNU449, and SNU475. Same genes and pathological features were also investigated in 49 samples of hepatitis B virus-related human HCCs. In all HCC cell lines studied, CD133-positive cells showed higher cell migration activity and up-regulated invasion- and EMT-associated genes with increased N-cadherin and decreased E-cadherin expressions compared to CD133-negative cells. The human HCCs were divided into the CD133-high group (top 40%) and the CD133-low group (bottom 40%) according to the level of CD133 mRNA. The CD133-high group showed relatively frequent vascular invasion and significantly higher expression of invasion-associated genes [uPAR (p = 0.002), MMP1 (p = 0.01), and MMP2 (p = 0.003)] and EMT regulators [Snail (p = 0.002) and Twist (p = 0.0003)] compared to the CD133-low group. In conclusion, our results suggest that there is a subtype of HCC with high expression of CD133, which might have more invasive characteristics by up-regulation of invasion-associated genes and EMT-associated genes.     

Testing ecological and universal models of body shape and child health using a global sample of infants and young children

Aim: To test whether a risk of child illness is best predicted by deviations from a population-specific growth distribution or a universal growth distribution.

Subjects and methods: Child weight for height and child illness data from 433 776 children (1–59 months) from 47 different low and lower income countries are used in regression models to estimate for each country the child basal weight for height. This study assesses the extent to which individuals within populations deviate from their basal slenderness. It uses correlation and regression techniques to estimate the relationship between child illness (diarrhoea, fever or cough) and basal weight for height, and residual weight for height.

Results: In bivariate tests, basal weight for height z-score did not predict the country level prevalence of child illness (r²?=?–0.01, n?=?47, p?=?0.53), but excess weight for height did (r²?=?0.14, p?p?n?=?433 776) and basal weight for height was not (beta?=?0.20, p?=?0.27). Deviations from country-specific basal weight for height were negatively associated with the likelihood of illness (beta?=?–0.13, p?Conclusion: These results are consistent with the idea that populations may differ in their body slenderness, and that deviations from this body form may predict the risk of childhood illness.     

Soluble type III TGFβ receptor in diagnosis and follow-up of patients with breast cancer

Abstract

Type III transforming growth factor (TGFβ) receptor (TGFβrIII) modulates TGFβ superfamily signaling. Its tumor tissue expression is downregulated in human breast cancer. We determined (indirect ELISA) plasma levels of the soluble receptor (sTGFβrIII) in 47 women with breast cancer (AJCC stages 0–IIB) (cases) pre-surgery and over two months after the surgery, and in 36 healthy women (controls). Plasma sTBFβrIII was lower in cases than in the controls (age-adjusted difference ?29.7?ng/mL, p?<?0.001), and discriminated between disease and health (sensitivity and specificity 100% at 16.6?ng/mL). With adjustment for age, AJCC stage, lymph node involvement, HER2 and hormone receptor status, higher pre-surgery sTBFβrIII was associated with better progression-free survival (HR?=?0.68, 95%CI 0.49–0.89, p?=?0.004). An increasing trend in plasma sTBFβrIII was observed over 2 months after the surgery (0.6% increase/day, p?<?0.001), consistently across the patient subsets. Data suggest a high potential of plasma sTBFβrIII as a novel diagnostic and prognostic biomarker in breast cancer.     

Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases

BackgroundIntrahepatic lymphatic invasion is an adverse prognostic factor after hepatectomy for colorectal liver metastases (CLMs). However, most patients in previous reports had liver resection before the era of FOLFOX/FIRI-based chemotherapy.MethodsForty-six patients who underwent hepatectomy for CLMs from 2004 to 2020 were evaluated. We histologically evaluated portal invasion, intrahepatic lymphatic invasion, and biliary invasion on hematoxylin-eosin slides. We also collected the following clinicopathologic factors: gender, age, timing, the number and maximum size of CLMs, preoperative tumor markers, neutrophil/lymphocyte ratio, location, and lymph node metastases of primary cancer, and chemotherapy after hepatectomy. A multivariate Cox proportional hazard model was used to define the relationship between overall (OS) or disease-free survival (DFS) and clinicopathologic factors.ResultsHistological invasions were portal invasion in 8 (17.4 %), intrahepatic lymphatic invasion in 6 (13.0 %), and biliary invasion in 5 (10.9 %). Chemotherapy for recurrence after hepatectomy (n = 29) was performed in 22 and 14 of those who received FOLFOX/FIRI-based chemotherapy. By multivariate analysis, the number of CLMs (p < 0. 01) and presence of intrahepatic lymphatic invasion (p = 0.02) were independent predictors of recurrence. The number of CLMs (p = 0.02) and prehepatectomy carcinoembryonic antigen level (p = 0.02), but not intrahepatic lymphatic invasion (p = 0.18), were independent predictors of survival using multivariate analysis.ConclusionsThe presence of intrahepatic lymphatic invasion adversely affected patient's DFS, but not OS in patients with CLMs in the era of FOLFOX/FIRI chemotherapy. FOLFOX/FIRI-based chemotherapy might improve OS, even in patients with positive intrahepatic lymphatic invasion.     

Tumor border pattern and size help predict lymph node status in papillary microcarcinoma: A clinicopathologic study

ObjectiveLymph node metastasis occurs in a subset of papillary microcarcinoma patients. We aimed to analyze the differences between metastatic and non-metastatic papillary microcarcinomas in order to identify a high-risk subgroup that is likely to require more aggressive treatment.Materials and methods126 thyroidectomies with lymph node dissections (central ± lateral), diagnosed as papillary microcarcinoma, were reviewed.ResultsMean age of 126 patients (F/M = 3.3) was 42 years. Mean size of the largest tumor was 7 mm. Classical was the most frequently (89%) encountered subtype. Multiple histologic subtypes co-occurred in 19%. Lymphovascular invasion was present in 16% (n = 20). 55 (44%) and 71 (56%) cases were unifocal and multifocal, respectively. 90 cases (71%) were non-encapsulated with overall infiltrative tumor borders, whereas in 36 cases (29%), the tumor had a well-defined capsule. Among those, 23 (64%) had tumor capsule invasion. 47 (37%) cases had metastasis in lymph nodes. In univariate analysis, metastasis was associated with tumor size of >5 mm (p = 0.02), tumor burden of >5 mm (p = 0.03), lymphovascular invasion (p = 0.02) and non-encapsulation (p = 0.01). No associations were found regarding sex, age, histologic subtype, lymphocytic thyroiditis, tumor capsule invasion (in capsulated tumors), laterality and multifocality (p > 0.05). In multivariate analysis, lymphovascular invasion (p = 0.01, OR = 3.97, 95% CI 1.35–11.67), tumor size >0.5 cm (p = 0.031, OR = 2.92, 95% CI 1.10–7.71) and non-encapsulation (p = 0.033, OR = 2.85, 95% CI 1.08–7.51) were independent risk factors.ConclusionSize (largest tumor or sum of all foci) of >5 mm, non-encapsulation and lymphovascular invasion were independent predictors of LNM in PMs. Unifocal tumors metastasize the same as multifocal tumors, suggestive of the contribution of other factors. Patients with sporadically resected microcarcinomas should be carefully followed-up, especially those that harbor risk factors in histology.     

Impact of Switching Virologically Suppressed,HIV-1-Infected Patients from Twice-Daily Fixed-Dose Zidovudine/Lamivudine to Once-Daily Fixed-Dose Tenofovir Disoproxil Fumarate/Emtricitabine

Abstract

Objective: Evaluate the impact of switching from twice-daily zidovudine/lamivudine (AZT/3TC) to once-daily tenofovir DF plus emtricitabine (TDF/FTC) with efavirenz (EFV). Design: Prospective, multicenter, single-arm 24-week trial. Methods: Patients on EFV + AZT/3TC for =8 weeks with HIV-1 RNA <400 copies/mL were switched to EFV + TDF/FTC and assessed for safety/tolerability, virologic and immunologic responses, adherence, and quality of life at 4, 12, and 24 weeks. Results: Of 402 patients, 2% discontinued for an adverse event (AE) and 1 patient for virologic failure. At 24 weeks, 87% had HIV RNA <400 copies/mL, and 74% versus 71% at baseline had undetectable (HIV RNA <50 copies/mL) viral load (ITT; M=F). Treatment-emergent AEs were infrequent (≤5%) with gastrointestinal complaints being the most common. At 24 weeks compared to baseline, hemoglobin (Hb) increased by a median of 0.6 g/dL (p < .001), and a decrease in creatinine clearance of 7.6 mL/min (p < .001) was observed. Fasting lipids decreased slightly (p < .02) in a subset of patients studied (n = 160). A higher percentage of patients reported being “very satisfied” with treatment and the absence of regimen side effects at 24 weeks versus baseline (p < .001). At 24 weeks, 86% of patients took ≥95% of doses versus 78% at baseline (p = .002). Conclusion: Patients switched to EFV + TDF/FTC maintained virologic suppression and the regimen was well tolerated. Patients reported increased satisfaction with treatment and fewer were bothered by side effects.     

Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum

In this experimental study, the effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum was investigated. A reproducible in vitro assay was developed to study the adhesion of CC531 colon carcinoma cells to an autologous monolayer of rat mesothelial cells. Tumour cell adhesion to mesothelium pre-incubated with interleukin-1beta (IL-1beta) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p相似文献   

Modulation of Transforming Growth Factor-β Actions in Rat Osteoblast-like Cells: The Effects of bFGF and EGF

Abstract

The present study examines how the mitogenic and differentiation functions of transforming growth factor-β (TGF-β) are modulated by basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in primary cultures of rat osteoblast-like (ROB) cells. TGF-β, bFGF, and EGF individually stimulated [³H]thymidine incorporation and cell proliferation in a dose range of 0.01-10 ng/ml. When studied in combination, high doses of bFGF and EGF were additive to low doses of TGF-β. The additive effects of bFGF and EGF on mitogenesis diminished with increasing doses of TGF-β. These three factors also decreased alkaline phosphatase activity individually within the same dose range. When cells were treated with the combined factors, only high doses of bFGF and EGF were additive to the TGF-β inhibition. We were unable to detect any change in collagen synthesis with each individual factor or in combined treatments. In addition, TGF-β or bFGF alone or in combination did not affect fibronectin synthesis. Our studies showed that the biological functions of TGF-β can be modulated by bFGF and EGF in ROB cells. The pattern of modulation is varied depending on the specific function examined.