Triple-Negative Breast Cancer is Not Associated with Increased Likelihood of Nodal Metastases

Background

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. The purpose of this study was to determine if patients with TNBC have a higher risk of lymph node (LN) metastases.

Methods

A prospective database review identified 3,289 patients treated with a mastectomy or with breast-conserving surgery between January 2000 and May 2012. The final analysis included those patients who underwent sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND), and the following information: age at diagnosis, tumor size, grade, stage, histologic subtype, presence of lymphovascular invasion (LVI), and the status of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2).

Results

A total of 2,967 patients met the inclusion criteria. SNB was performed in 1,094 patients, ALND in 756, and both SNB and ALND in 1,117 patients. LN metastases were detected in 1,050 (35 %) patients. On univariate analysis, the LN positivity varied across subtypes with 33 % in luminal A, 42 % in luminal B, 39 % in TNBC, and 45 % in HER-2 (p = 0.0007). However, on multivariable analysis, there was no difference in LN positivity among subtypes. Age <50, grade 2 or 3 tumors, size ≥2 cm, and presence of LVI were significant predictors of LN positivity. Four or more involved nodes were observed most commonly in the HER2 (19.4 %) and luminal B (13.7 %) subtypes, but only 9.4 % in TNBC (p < 0.0001).

Conclusions

Predictors of LN metastases include younger age, higher grade, larger tumor size, and presence of LVI. Patients with TNBC are not more likely to have involved nodes than those with non-TNBC.     

Peep and the bain circuit

The feasibility of applying positive end expiratory pressure within the Bain circuit using an Emerson PEEP valve was studied. It was determined that varying degrees of PEEP may be applied within the Bain circuit using an Emerson PEEP valve during either mechanically or manually controlled ventilation but not during spontaneous breathing. There was some loss of measured tidal volume with increasing PEEP, due primarily to compression gas losses but also from leakage throughout the system. The maximum gas loss was 100 ml per minute at PEEP 15 cm H₂O under test conditions. PEEP may be applied between the Bain tubing and the manifold. However, one should then never allow the patient to breathe spontaneously as the PEEP valve presents an obstruction to inspiratory flow. With the PEEP valve relocated between the Bain manifold and the ventilator hose it was found that application of PEEP was possible without this disadvantage, but only during mechanical ventilation.     

Effects of ethylenediaminetetraacetate (EDTA) on urinary excretion of hydroxyproline,calcium and phosphorus in the rat

The effects of ethylenediaminetetraacetate (EDTA) were studied in rats. Intravenous infusion of 4.84 mM Na₂EDTA increased the urinary excretion of calcium six-fold, phosphorus three-fold and hydroxyproline 55% in 158 g thyroparathyroidectomized (TPTXed) rats. Calcitonin (25 MRC mU/rat/h) abolished the sodium EDTA-induced increase in hydroxyproline excretion, presumptive evidence that sodium EDTA was acting on bone. To determine whether the changes induced by sodium EDTA are due to lowering of plasma calcium, rats were infused with 4.84 mM ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), a more specific calcium chelator. EGTA increased the urinary excretion of calcium and phosphorus (P<0.001) but not hydroxyproline in thyroparathyroidectomized rats. Furthermore, when TPTXed rats were infused with calcium EDTA (4.84 mM Ca₂EDTA) in order that ionic calcium concentration would not be altered, hydroxyproline excretion was again markedly increased but phosphorus excretion was decreased by 26%. Since the displacement of the sodium ions in Na₂EDTA by calciumin vivo is instantaneous, and since calcium EDTA itself induces collagenolysis, the increase in urinary hydroxyproline excretion due to sodium EDTA cannot be attributed solely to lowering of plasma calcium. From these data two conclusions are drawn. First, sodium EDTA enhances bone breakdown independently of its effect on parathyroid hormone secretion. Second, since bone plays a major role in the maintenance of plasma calcium, interpretation of results should be made with caution in those investigations in which EDTA is used to study calcium homeostasis.     

Acetylcholinesterase activity in rectal mucosa and blood in the diagnosis of Hirschsprung's disease

Histochemical and biochemical examinations of rectal biopsy specimens were performed in 13 patients with Hirschsprung's disease and in seven with idiopathic constipation and no megacolon. Serum and erythrocyte acetylcholinesterase (AchE) activity in these two groups was compared with that in 30 normal controls. AchE staining of rectal biopsy specimens proved to be a reliable and convenient diagnostic approach in patients with Hirschsprung's disease. Biochemical assay of AchE activity in rectal biopsy specimens was also of value in the diagnosis, however, there was an overlap between Hirschsprung's disease and idiopathic constipation. Erythrocyte AchE activity correlated well with AchE activity in rectal biopsy specimens. Therefore, assays of erythrocyte AchE activity provided useful additional information, especially in screening tests for Hirschsprung's disease.     

IGF-2 Is Necessary for Retinoblastoma-Mediated Enhanced Adaptation after Small-Bowel Resection

Previously, we have demonstrated that genetically disrupting retinoblastoma protein (Rb) expression in enterocytes results in taller villi, mimicking resection-induced adaption responses. Rb deficiency also results in elevated insulin-like growth factor-2 (IGF-2) expression in villus enterocytes. We propose that postoperative disruption of Rb results in enhanced adaptation which is driven by IGF-2. Inducible, intestine-specific Rb-null mice (iRbIKO) and wild-type (WT) littermates underwent a 50 % proximal small-bowel resection (SBR) at 7–9 weeks of age. They were then given tamoxifen on postoperative days (PODs) 4–6 and harvested on POD 28. The experiment was then repeated on double knockouts of both IGF-2 and Rb (IGF-2 null/iRbIKO). iRbIKO mice demonstrated enhanced resection-induced adaptive villus growth after SBR and increased IGF-2 messenger RNA (mRNA) in ileal villus enterocytes compared to their WT littermates. In the IGF-2 null/iRbIKO double-knockout mice, there was no additional villus growth beyond what was expected of normal resection-induced adaptation. Adult mice in which Rb is inducibly deleted from the intestinal epithelium following SBR have augmented adaptive growth. IGF-2 expression is necessary for enhanced adaptation associated with acute intestinal Rb deficiency.     

Effects of laser irradiation at different wavelengths (660, 810, 980, and 1,064 nm) on mucositis in an animal model of wound healing

The aim of the present study was to compare the effectiveness of four different laser wavelengths (660, 810, 980, and 1,064 nm) used for low-level laser therapy (LLLT) on the healing of mucositis in an animal model of wound healing by investigating the expression of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and blood-derived fibroblast growth factor (bFGF). Thirty-five male Wistar albino rats with a weight of 250–300 g body mass and 5 months old were used in the study. All animals were intraperitoneally injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tip of an 18-gauge needle was used in order to develop a superficial scratching on the left cheek pouch mucosa by dragging twice in a linear movement on third and fifth days. After ulcerative mucositis were clinically detected on the animals' left cheek pouch mucosa, the laser therapy was started. Four different laser wavelengths (660 nm, HELBO, Bredent; 810 nm, Fotona XD, Fotona; 980 nm, ARC Fox; and 1,064 nm, Fidelis Plus 3, Fotona) used for LLLT at ED 8 J/cm² daily from the first to the fourth days. Oval excisional biopsy was taken from the site of the wound, and the expression of PDGF, TGF-β, and bFGF was evaluated. The obtained data were analyzed by one2-way ANOVA, and then Tukey HSD tests were used for pairwise comparisons among groups (α?=?0.05). The one-way ANOVA test indicated that expression values of the growth factors, PDGF and bFGF, were significantly affected by irradiation of different wavelengths of lasers (p?TGF-β was not affected by irradiation of different wavelengths of lasers (p?>?0.05). The highest PDGF expression was detected in neodymium-doped yttrium aluminum garnet (Nd:YAG) laser group (p?p?>?0.05). The highest bFGF expression was detected in 980-nm diode and Nd:YAG laser groups (p?p?>?0.05). These findings suggest that low-level Nd:YAG and 980-nm diode laser therapy accelerate the wound healing process by changing the expression of PDGF and bFGF genes responsible for the stimulation of the cell proliferation and fibroblast growth.     

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Background

The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

Methods

We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

Results

Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

Conclusion

Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.     

CD147-CD98hc Complex Contributes to Poor Prognosis of Non-Small Cell Lung Cancer Patients Through Promoting Cell Proliferation Via the PI3K/Akt Signaling Pathway

Background

It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated.

Methods

The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation.

Results

Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p < 0.001). Immunoflurenece staining and co-immunoprecipitation demonstrated that CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147?/CD98hc?, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc.

Conclusions

Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.     

Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.     

Isoflurane anaesthesia for a patient with long Q-T syndrome

A case report of a patient known to have long Q-T syndrome (LQTS) undergoing elective oral surgery is presented. While nitrous oxide-narcotic, nitrous oxide-enflurane, or nitrous oxide-halothane techniques for anaesthetic management of LQTS have been previously reported, we report the use of nitrous oxide-isoflurane for the maintenance of anaesthesia. The authors feel that isoflurane is a safe anaesthetic agent for use in LQTS.     

The effect of noggin interference in a rabbit posterolateral spinal fusion model

Study design

Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle.

Objective

To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits.

Summary of background data

Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown.

Methods

A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks.

Results

SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.).

Conclusions

Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.     

HbA1c and survival in maintenance hemodialysis patients with diabetes in Han Chinese population

Background

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). The aim of this study was to investigate the association between HbA1c and survival in diabetic MHD patients in Han Chinese population.

Methods

A 5-year cohort (October 2007–December 2013) of 236 diabetic MHD patients with HbA1c data was examined for associations between HbA1c and mortality. Death hazard ratios (HR) were estimated using Cox regressions.

Results

Two hundred and thirty-six diabetes patients undergoing MHD in clinics over 5 years were included in our study. Unadjusted survival analyses indicated paradoxically lower death HRs with higher HbA1c values. However, after adjusting for potential confounders (demographics, dialysis vintage, comorbidity, anemia, and inflammation), higher HbA1c values were incrementally associated with higher death risks.

Conclusions

Poor glycemic control (HbA1c ≥ 8 %) appears to be associated with decreased survival in the general population of diabetic MHD patients. Our study suggests that moderate hyperglycemia increases the risk for all-cause mortality of diabetic MHD patients in Han Chinese population.     

The True Incidence of Gastric GIST—a Study Based on Morbidly Obese Patients Undergoing Sleeve Gastrectomy

Background

Gastrointestinal stromal tumor (GIST) is a rare neoplasm of the alimentary tract. Previous reports described an incidence of 1 per 100,000. Laparoscopic sleeve gastrectomy (LSG) provides pathological specimens of the majority of the stomach. We examined the pathology from LSG and the incidence and location of GIST. The aim of this study was to study the incidence of asymptomatic GISTs found during LSG at our institution.

Methods

A search was conducted in a prospectively maintained bariatric registry. Data collected included the following: gender, age, body mass index (BMI), and concomitant hypertension or diabetes mellitus. Histopathology reports were reviewed for incidental GIST. We compared the patients with incidental GIST to the rest of the cohort.

Results

Pathology reports of 827 patients that underwent LSG between 2007 and 2014 were reviewed. Five patients had GIST in the resected stomach, an incidence of 0.6 %. The group of patients with GIST had lower BMI and older age compared to the remaining 822 patients. All tumors were located close to the lesser curvature.

Conclusions

The incidence of GIST found in this cohort is significantly higher than previously reported. This may be due to an association between these tumors and obesity or because asymptomatic GISTs are underdiagnosed in the general population. These tumors are particularly common in older patients and special attention must be given when performing LSG on this subpopulation. The stomach should be inspected thoroughly before resection. A tumor on the lesser curvature may necessitate changing the surgical plan or aborting the procedure.     

Melatonin improves functional outcome via inhibition of matrix metalloproteinases-9 after photothrombotic spinal cord injury in rats

Background

Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 play an important role in secondary inflammatory reaction and blood–central nervous system (CNS) barrier disruption after spinal cord injury (SCI). Theoretically, it is expected that early blockade of activation of MMPs can provide neuro-protective effects from secondary tissue damage and improve functional neurological outcomes. The aim of this study was to investigate the expression and the activity of MMP-2 and MMP-9, and to determine the regulatory effect of melatonin on MMP expression and activity after photochemically induced SCI in rats.

Methods

Female Sprague–Dawley rats weighing between 250 and 300 g (age 8 weeks) received focal ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups; one group received 50 mg/kg of melatonin intraperitoneally, starting 1 h after injury and at 12 h intervals for 7 days, while animals in the control group received weight-adjusted doses of a saline vehicle. In each group, the expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 3 days. The locomotor function was assessed using the Basso-Beattie-Bresnahan (BBB) scale at 3 days after SCI and then once per week for 4 weeks. The animals were killed at 28 days after the injury, and the histopathology of the lesions was assessed.

Findings

The expressions and activities of MMP-9 were increased at 6, 24, 48, and 72 h after SCI in the control group. In the melatonin-treated group, the expression of MMP-9 was significantly decreased at 24, 48, and 72 h after SCI compared with the control group, and the activity of MMP-9 was significantly reduced at 72 h after SCI. In contrast, there were no significant changes in the MMP-2 level in both groups during the experimental period. Melatonin treatment following photochemically induced SCI in rats significantly ameliorated the functional deficits. On histopathologic examination, the lesion size in the spinal cord after photothrombotic insult was significantly reduced by melatonin administration.

Conclusions

This study showed that the up-regulation of MMP-9 correlated with the secondary damage after SCI in rats. The results of this study suggest that the ability of melatonin to reduce secondary tissue damage is intimately related to the reduction of MMP-9 expression, resulting in functional improvement.     

A Nomogram to Predict Disease-Free Survival After Surgical Resection of GIST

Background

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy has resulted in improved disease-free survival (DFS) following resection of primary GIST. The aim of our study was to create a nomogram to predict DFS following resection of GIST.

Method

Using a multi-institutional cohort of patients who underwent surgery for primary GIST at 7 academic hospitals in the USA and Canada between January 1998 and December 2012, a multivariable Cox proportional hazards model predicting DFS was created using backward stepwise selection. A nomogram to predict DFS following surgical resection of GIST was constructed with the variables selected in the multivariable model. We tested nomogram discrimination by calculating the C-statistic and compared the nomogram to four existing GIST prognostic stratification systems.

Results

A total of 365 patients who underwent surgery for primary GIST was included in the study. Using backward stepwise selection, sex, tumor size, tumor site, and mitotic rate were selected for incorporation into the nomogram. The nomogram demonstrated superior discrimination compared to the NIH criteria, modified NIH criteria, and Memorial Sloan-Kettering Nomogram and had similar discrimination to the Miettinen criteria (C-statistic 0.77 vs 0.73, 0.71, 0.71, and 0.78, respectively).

Conclusion

Four independent predictors of recurrence following surgery for primary GIST were used to create a nomogram to predict DFS. The nomogram stratified patients into prognostic groups and performed well on internal validation.     

The effect of diclofenac on matrix metalloproteinase levels in the rotator cuff

Introduction

Matrix metalloproteinases (MMPs) are involved in physiological events such as restructuring of the tissue, morphogenesis, wound healing and normal developmental process. Use of diclofenac sodium following rotator cuff repair can disrupt healing of tendon through acting on MMPs.

Materials and methods

Supraspinatus tendons of rats (n = 84) were detached from their insertion on humerus, and repaired to anatomic footprint. Rats were divided into study group (n = 42) and control group (n = 42). Study group received a dose of 1 mg/kg daily diclofenac sodium subcutaneously. The rats were killed at weeks 1, 3 and 6, and seven rats from each groups were included in biomechanical and immunohistological examinations. Immunohistological staining of MMP-2, MMP-3 and MMP13 were used.

Results

Maximum load was reduced in the study group at the end of week 1 (8.76 vs. 5.28 N) (p = 0.01). MMP-3 level was statistically significantly lower in the study group at the end of week 1. MMP-13 level and stiffness decreased towards week 6 in the study group while in the control group the level of MMP-2 decreased towards week 6.

Conclusion

Diclofenac has an impact on the levels of MMP-2, MMP-3 and MMP-13, which are needed for normal healing process, and it can also lead to disruption of tendon healing.     

Diagnostic evaluation of CT and ERCP based on a retrospective analysis of hepato-biliary and pancreatic diseases

A retrospective analysis was performed in order to evaluate diagnostic accuracies by computed tomography (CT) and by endoscopic retrograde cholangiopancreatography (ERCP). Materials studied were 67 lesions out of 56 cases with hepato-biliary and pancreatic diseases confirmed mainly at surgery. Diagnostic accuracy of the CT & ERCP for the hepatobiliary lesions was 59.5% & 86.5% and that of CT & ERCP for the pancreatic lesions was 60% & 80% respectively. CT scan is useful for diagnosing abscess, cyst or tumors. On the contrary, lesions which invade the hepatobiliary tract or pancreatic duct can be readily diagnosed by ERCP examination. ERCP is less useful for the diagnosis of parenchymatous lesions or infiltration of lesions into the surrounding organs. Therefore, the combined use of both CT and ERCP is important for the diagnosis of hepato-biliary or pancreatic disease.     

Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats

Purpose

To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)–nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.

Methods

Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD-IRES-EGFP as control. Blood and urine samples were collected. Endothelium-dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively.

Results

Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF–NO axis was partially improved by AD-AdipoQ.

Conclusion

Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF–NO axis in early diabetic nephropathy.     

Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma

Purpose

To clarify whether vascular endothelial growth factor receptor 2 (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival.

Methods

All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival (OS) were analyzed.

Results

A series of 40 chordoma patients who underwent surgery for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5 %, lumbar spine 17.5 %, cervical/thoracic spine 5 %). Surgical margins were wide in 30 (75 %), marginal in 8 (20 %) and intralesional in 2 (5 %) patients. Median follow-up was 120 months. The 5- and 10-year OS of the entire series of patients was 78.6 and 30 %, respectively. There were five primary chordomas (12.5 %) with moderate and 35 (87.5 %) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5 %) with moderate and 25 tumors (62.5 %) with strong expression. All recurrent chordomas displayed strong expression of iNOS.

Conclusion

The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10 years was only 30 %.