Normal Peripheral Tissue Research Articles

Oncogenic miR-9 is a target of erlotinib in NSCLCs.

EGFR-targeted cancer therapy is a breakthrough in non-small cell carcinoma. miRNAs have been proved to play important roles in cancer. Currently, for the role of miRNAs in EGFR-targeted cancer therapy is unclear. In this study, first we found that erlotinib reduced the expression of miR-9. MiR-9 expression was increased in human lung cancer tissues compared with peripheral normal tissues, and miR-9 promoted the growth of NSCLC cells. Overexpression of miR-9 decreased the growth inhibitory effect of erlotinib. Second, miR-9 decreased FoxO1 expression by directly inhibition of its mRNA translation. Adenovirus-mediated overexpression of FoxO1 or siRNA-mediated downregulation of FoxO1 negatively regulated cell growth. And exogenous overexpression FoxO1 reduced the pro-growth effect of miR-9. Finally, we found that erlotinib upregulated FoxO1 protein expression. Moreover, overexpression of miR-9 decreased erlotinib-induced FoxO1 expression, and overexpression of FoxO1 enhanced the growth inhibitory effects of erlotinib. Additionally, we found that erlotinib downregulates miR-9 expression through suppressing the transcrption of miR-9-1 and enhanced DNA methylation maybe involved. These findings suggest that oncogenic miR-9 targeted FoxO1 to promote cell growth, and downregulation of this axis was involved in erlotinib’s growth inhibitory effects. Clarifying the regulation of miRNAs by erlotinib may indicate novel strategies for enhancing EGFR-targeted cancer therapy.

Pharmacokinetic analysis of prostate cancer using independent component analysis

Dynamic contrast enhanced (DCE)-MRI combined with pharmacokinetic (PK) modeling of a tumor provides information about its perfusion and vascular permeability. Most PK models require the time course of contrast agent concentration in blood plasma as an input, which cannot be measured directly at the tissue of interest, and is approximated with an arterial input function (AIF). Variability in methods used in estimating the AIF and inter-observer variability in region of interest selection are major sources of discrepancy between different studies. This study had two aims. The first was to determine whether a local vascular input function (VIF) estimated using an adaptive complex independent component analysis (AC-ICA) algorithm could be used to estimate PK parameters from clinical dynamic contrast enhanced (DCE)-MRI studies. The second aim was to determine whether normalizing the input function using its area under the curve would improve the results of PK analysis. AC-ICA was applied to DCE-MRI of 27 prostate cancer patients and the intravascular signal was estimated. This signal was converted into contrast agent concentration to give a local vascular input function (VIF) which was used as the input function for PK analysis. We compared Ktrans values for normal peripheral zone (PZ) and tumor tissues using the local VIF with those calculated using a conventional AIF obtained from the femoral artery. We also compared the Ktrans values obtained from the un-normalized input functions with the KNtrans values obtained after normalizing the AIF and local VIF. Normalization of the input function resulted in smaller variation in PK parameters (KNtrans vs. Ktrans for normal PZ tissue was 0.20±0.04mM.min−1 vs. 0.87±0.54min−1 for local VIF and 0.21±0.07mM.min−1 vs. 0.25±0.29min−1 for AIF) and better separation of the normal and tumor tissues (effect-size of this separation using KNtrans vs. Ktrans was 0.89 vs. 0.75 for local VIF and 0.94 vs. 0.41 for AIF). The AC-ICA and AIF-based analyses provided similar (KNtrans) values in normal PZ tissue of prostate across patients. Normalizing the input function before PK analysis significantly improved the reproducibility of the PK parameters and increased the separation between normal and tumor tissues. Using AC-ICA allows a local VIF to be estimated and the resulting PK parameters are similar to those obtained using a more conventional AIF; this may be valuable in studies where an artery is not available in the field of view.

Abstract 1068: Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue

Abstract Aberrant DNA methylation in peripheral blood cells (PBCs) may be a potential noninvasive biomarker for breast cancer risk. Whether methylations at CpG sites in PBCs can serve as proxies in normal breast tissues are unknown. We evaluated the correlation of DNA methylation between PBC DNA and breast cancer adjacent normal tissue using data and samples from the Shanghai Breast Cancer Study. Genome-wide DNA methylation profiles in PBCs and matched tumor adjacent normal tissues from 31 breast cancer patients were assayed using Illumina HumanMethylation450 BeadChip, which includes >485,000 CpG sites and covers 99% of RefSeq genes with multiple probes per gene. After quality control filtering, a total of 432,513 CpG sites were retained for analysis. We evaluated the association of methylation for each CpG site between DNA samples for PBCs and normal breast tissue using Spearman's rank correlation (r). The overall median correlation (r) is 0.35. A total of 99,928 (23.1%) and 18,290 (4.2%) of CpG sites had a high correlation between PBC DNA and normal breast tissue DNA with r > 0.50 and r > 0.75, respectively. Interestingly, we found that the correlation was negatively associated with both methylation levels (mean) and inter-person variability (standard deviation) in normal breast tissues (ρ = -0.14 and -0.19; P < 2.2 x10-16 for both). In 926 previously reported methylation quantitative trait loci, the correlations between PBCs and normal breast tissue were significantly higher (median r = 0.42) than the remaining loci (median r = 0.34) (Wilcoxon test, P < 2.2 x10-16), suggesting that methylation variations controlled by genetic variations exhibited a robust correlation between PBC and normal breast tissue DNA. In summary, our results suggest that the methylation status of CpG sites with large inter-person variations or genetically-controlled variations in PBC DNA correlate well with those in normal breast tissue. This supports the conduct of a genome-wide methylation study for breast cancer using PBC DNA. Citation Format: Xingyi Guo, Xiao-Ou Shu, Chun Li, Jirong Long, Bingshan Li, Yu-Tang Gao, Wei Zheng, Qiuyin Cai. Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1068. doi:10.1158/1538-7445.AM2015-1068

Preliminary Study of Expression of KL-6, FGF-10 and MMP-9 in the Primary Spontaneous Pneumothorax

Objective: Pathogenesis of primary spontaneous pneumothorax (PSP) is unclear and has been rarely reported in the literature. Thus, we measured expression of Krebs Vonden Lungen-6 (KL-6), fibroblast growth factor-10 (FGF-10), and matrix metalloproteinase-9 (MMP-9) in PSP samples and evaluated their significance on the development and progress of the disease. Methods: Immunohistochemical staining and ELISA were used to measure expression of KL-6, FGF-10, and MMP-9 in the pulmonary bullae and the peripheral normal lung tissue in 24 cases of PSP. Statistical results were analyzed using the Student’s paired t-test. Results: Immunohistochemical data revealed that KL-6 and FGF10 expression in the pulmonary bullae was significantly higher than in peripheral normal lung tissue, but MMP-9 expression did not differ. ELISA confirmed that KL-6 and FGF-10 expression in the pulmonary bullae was significantly higher than the peripheral normal lung tissue (P 0.05). Conclusion: Expression of KL-6 and FGF-10 in pulmonary bullae of PSP patients was significantly higher than in the peripheral normal lung tissue, suggesting that KL-6-mediated pulmonary fibrosis and abnormal FGF-10 expression-induced congenital abnormalities in development of bronchi may be associated with PSP. MMP-9 was not different in both groups, suggesting that further correlation between MMP-9-mediated inflammation and PSP remains unclear.

Localized thermal tumor destruction using dye-enhanced photothermal tumor therapy.

In an attempt to develop a new therapeutic approach for highly localized thermal destruction of tissue targets that lack natural pigmentation, the potential of in-vivo dye-enhanced photothermal therapy (PTT) was investigated. PTT involves the application of an exogenous absorber, which accumulates in metabolically active tissues, followed by non-invasive light irradiation, using appropriate wavelengths, exposure durations, and irradiances. The chromophore used, palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8 ), strongly absorbs in the near infrared wavelength range which thus permits good penetration depth of the exciting light. The predominant de-excitation routes of the chromophore are radiationless thermal processes. Using a BALB/c mouse model with a subcutaneously implanted syngeneic EMT6 adenocarcinoma, 96-100 hours after intraperitoneal application of PdNc(OBu)8 , tumor, and surrounding tissue were irradiated with a 830 nm continuous wave diode laser applying 30 Wcm(-2) for 10-20 seconds. Treatment parameters were based on theoretical calculations. Histological evaluation of thermal effects on tumor and normal tissue showed that after PdNc(OBu)8 -enhanced photothermal treatment, highly localized and selective thermal damage of the tumors was achieved. The necrotic tumor area was invaded by inflammatory cells, including neutrophils, macrophages, mast cells, and lymphocytes, thus reflecting a prominent host immune response. In tumors treated with PTT for 15 or 20 seconds, respectively, only few surviving tumor cells were detected underneath the epidermis. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. This study highlights the potential of achieving irreversible thermal tissue damage closely localized to the target tissue when PdNc(OBu)8 is used in combination with continuous-wave light.

Human alveolar epithelial type II cells in primary culture.

Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.

In vivo imaging and characterization of [18F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET

IntroductionThe translocator protein 18kDa (TSPO), a biochemical marker of neuroinflammation, is highly expressed in the brain activated microglia and it is also expressed by peripheral inflammatory cells and normal peripheral tissues. Thus, development of radioligands for the TSPO may contribute to further understanding the in vivo TSPO function in central and peripheral inflammatory processes and other pathologies. Here, we report the biodistribution, the specific binding and the radiometabolites of [18F]DPA-714, a promising fluorinated PET radiotracer, in normal mice using a microPET/CT scanner. MethodsThe in vivo biodistribution and kinetics of [18F]DPA-714 were measured in mice brain and peripheral tissues. Specific binding to TSPO sites was assessed using pharmacological competitive studies by means of saturation experiments performed by i.v. injection of 1mg/kg of unlabeled DPA-714 or 3mg/kg of unlabeled PK11195. A region of interest analysis was performed to generate time-activity curves in the brain, heart, lung, kidney, spleen and liver. Metabolites assay was performed in the plasma and peripheral organs by radio-HPLC. Results[18F]DPA-714 reached high concentration in lung, heart, kidney and spleen, tissues well known to be rich in TSPO sites. [18F]DPA-714 kinetics were faster in the lung and slower in the kidney. Pre-injection of unlabeled DPA-714 or PK11195 inhibited about 80% of [18F]DPA-714 uptake in the lung and heart (p<0.0005). The percentage of inhibition in the kidney was lower and achieved at later times only with DPA-714 (p<0.05) but not with PK11195. Sixty minutes after radiotracer injection only unmetabolized radioligand was found in the brain, lung, heart and spleen. ConclusionThese results suggest that [18F]DPA-714 is a suitable PET ligand for imaging in mice brain and peripheral tissues since it binds with high specificity TSPO binding sites and it is almost unchanged at 60minutes after radiotracer injection in the brain and TSPO-rich regions.

Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.

Expression of Urocortin I in Normal Tissues and Malignant Tumors

Corticotropin-releasing factor (CRF) is a key player in the hypothalamus-pituitary adrenal axis, and exerts its actions through two types of receptors: CRF type 1 and type 2 (CRF1 and CRF2) receptors. After the discovery of CRF and these receptors, a CRF-related peptide, urocortin I (UCN I), was identified. UCN I is a more potent agonist than CRF on CRF receptors, especially CRF2, which is involved in stress response. UCN I has various beneficial actions and is distributed in central and peripheral normal tissues, including the brain, heart, vascular cells, and endometrium. Recently, UCN I expression was also discovered in malignant cells, such as human glioblastoma cells, pituitary adenoma cells, hepatic carcinoma cells, gastric cancer cells, adrenocortical adenoma cells, and renal clear-cell carcinoma cells. Recent developments into the pathophysiological roles of UCN I and its related peptides will potentially lead to new anticancer therapies. Here, we review the expression of UCN I in normal and malignant cells and discuss the future of UCNs in anticancer therapy.

FOXP1 has a low expression in human gliomas and its overexpression inhibits proliferation, invasion and migration of human glioma U251 cells.

The present study aimed to examine the clinical characteristics of forkhead box protein P1 (FoxP1) in gliomas and its role in the proliferation, invasiveness, migration and apoptosis of the human glioma U251 cell line. The expression levels of FOXP1 were first studied in operation resection specimens of glioma and normal peripheral brain tissues. The enhanced green fluorescent protein (EGFP) expression vector of FOXP1 was prepared and transfected into U251 cells. MTT, cell invasion, transwell and scratch assays were utilized to investigate the cell growth activity and the rate of apoptosis of the cells was tested by flow cytometry. Western blot analysis and quantitative polymerase chain reaction assays were employed to measure the transfection efficacy. The results revealed that FOXP1 was highly expressed in glioma, as compared with low levels detected in normal brain tissues. Following transfection with pEGFP-N1-FOXP1, the proliferation, invasiveness and migration capabilities of cells significantly decreased, whilst the rate of apoptosis was markedly enhanced (P<0.01). Furthermore, the expression of FOXP1 in U251 cells was enhanced (P<0.01). In conclusion, the present study indicated that FOXP1 is closely associated with tumorigenesis and development of glioma, as demonstrated by a reduction in the proliferation, migration and invasion of glioma cells upon FOCP1 overexpression.

Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Confirmatory correlation between the nominal target radius (ie, RT) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/RT, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R(2) >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55%±16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/RT values for the target. Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.

Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients

CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman’s rank test. Agreement was determined by generalized κ-statistics. Spearman’s rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

Application of Cicatricial Contracture Release Principles in Muscular Torticollis Treatment

Numerous surgical approaches for muscular torticollis are not effective enough to completely release the contracture and prevent further development of craniofacial asymmetry. Cosmetically unacceptable scars on the neck and compulsory functional exercises after surgery were also common problems. We applied the therapeutic principle of scar contracture to the surgical treatment of muscular torticollis. Surgical incision determination and the postoperative protocol were considerably improved. Satisfactory results were obtained. According to the therapeutic principle of scar contracture, complete release of the contracted muscles and peripheral streak fascia and release or partial resection of peripheral normal tissues such as the scalenus anterior, anterior trapezius border, platysma, and partial carotid sheath are required to release all the affected contracted and tightened tissues. We chose to incise underneath the affected side of the clavicular border. We obtained a tension-free closure of the incision through an advanced skin flap of the inferior incision sutured on the clavicular fascia. Maximum head and neck stretch to the unaffected side of the shoulder when the patient lied down gave the affected side lateral decubitus position after surgery. Satisfactory results were obtained and no complications were identified for all of the 104 patients. The development of craniofacial asymmetry and progressive deformities was prevented. The incision scar appeared linear in the pit above or below the clavicle border and was relatively inconspicuous. The application of the therapeutic principle of scar contracture to the surgical treatment of muscular torticollis was successful.

Effect of unilateral diaphragmatic paralysis on postpneumonectomy lung growth.

Respiratory muscle-associated stretch has been implicated in normal lung development (fetal breathing movements) and postpneumonectomy lung growth. To test the hypothesis that mechanical stretch from diaphragmatic contraction contributes to lung growth, we performed left phrenic nerve transections (PNT) in mice with and without ipsilateral pneumonectomy. PNT was demonstrated by asymmetric costal margin excursion and confirmed at autopsy. In mice with two lungs, PNT was associated with a decrease in ipsilateral lung volume (P<0.05) and lung weight (P<0.05). After pneumonectomy, PNT was not associated with a change in activity level, measureable hypoxemia, or altered minute ventilation; however, microCT scanning demonstrated altered displacement and underinflation of the cardiac lobe within the first week after pneumonectomy. Coincident with the altered structural realignment, lung impedance measurements, fitted to the constant-phase model, demonstrated elevated airway resistance (P<0.05), but normal peripheral tissue resistance (P>0.05). Most important, PNT appeared to abrogate compensatory lung growth after pneumonectomy; the weight of the lobes of the right lung was significantly less than pneumonectomy alone (P<0.001) and indistinguishable from nonsurgical controls (P>0.05). We conclude that the cyclic stretch associated with diaphragmatic muscle contraction is a controlling factor in postpneumonectomy compensatory lung growth.

Surgeon leadership enables development of a colorectal cancer biorepository

BackgroundWe hypothesized that surgeons can improve the collection of all necessary elements (tissue and clinical data) needed to build a complete, robust research biorepository. MethodsAll colorectal cancer patients treated at a university medical center and its affiliates were eligible for inclusion. Data were collected from an 18-page personal and family health questionnaire, a prospectively maintained clinical database, and molecular testing. Tissues included serum, plasma and peripheral blood mononuclear cells, and tumor and normal tissue. We compared 2 groups: the surgeon-referred group and the other clinician–referred group. The primary outcome was the complete collection of data (ie, preoperative/staging clinical data, blood samples, and tissue collection). Statistical analysis was performed using the Student t test. ResultsSince 2006, 452 patients were approached, and 430 (95%) have been enrolled. Of these, 124 were referred by their surgeon, and 306 were consented in a clinic or over the telephone. Of patients referred by their surgeon, tumor tissue, blood samples, and preoperative/staging clinical data were obtained in 119 patients; conversely, in patients referred by oncologists or other clinicians, only 133 patients had complete data (96% vs 43.5%, P < .05). A total of 257 tissue samples were obtained from all patients. Additional testing has been performed on 228 specimens including immunohistochemistry, microsatellite testing, and genotype mutational analysis. ConclusionsSurgeon-directed enrollment in a biorepository improves the ability to collect blood and tissue samples. Surgeons should take a leadership role in the development of tumor biorepositories.

Osteosarcoma Around the Knee Treated With Neoadjuvant Chemotherapy and a Custom-designed Prosthesis

This article describes a novel approach using high-dose neoadjuvant chemotherapy with wide tissue resection and a specially designed artificial joint in 104 patients with stage IIB osteosarcoma near the knee. Sixty-four lesions were located at the distal femur, 39 at the proximal tibia, and 1 invaded the proximal tibia from the distal femur. Pathological fracture was present in 9 patients. Three courses of high-dose methotrexate, doxorubicin, and ifosfamide were administered preoperatively, and 6 courses were administered postoperatively. Preoperative radiographs and magnetic resonance images were obtained to determine the required tumor resection range and prosthesis size. Osteotomy of 3 cm of normal bone outside the tumor and wide resection of normal peripheral soft tissue were performed. Reconstruction with a rotary hinge or simple hinge prosthesis, as appropriate, was then performed. The Musculoskeletal Tumor Society 93 scoring system was used to evaluate limb function 6 months postoperatively. At final follow-up, recurrence, complication, survival, and amputation rates were 4%, 18%, 85%, and 4%, respectively. No recurrences were observed at the ends of amputated bones. Complications included infection (6%), nerve injury (3%), and prosthesis-related events (2% dislocation, 3% breakage, and 1% dislocation-related). Mean Musculoskeletal Tumor Society 93 score was 28 points, which indicated an excellent functional outcome. The low recurrence rate is attributed to the efficacy of the chemotherapy and the accuracy of the margin of resection.Effective chemotherapy reduces the risk of tumor metastasis and clarifies the tumor margin. Accurate identification of the resection margin reduces the risk of local recurrence.

Significance of Bcl10 gene mutations in the clinical diagnosis of MALT-type ocular adnexal lymphoma in the Chinese population

We investigated the expression of Bcl10 gene mutations in mucosa-associated lymphoid tissue-type ocular adnexal lymphoma (OAL), atypical lymphoid hyperplasia (ALH), and reactive lymphoid hyperplasia (RLH) in the Chinese population and its role in clinical diagnosis and pathogenesis. Forty-three samples were collected during patient surgeries. Pathological diagnosis confirmed OAL in 23 cases, ALH in 10 cases, and RLH in 10 cases. Normal peripheral lymph tissues from 12 cases were used as negative controls. Bcl10 gene expression was examined using molecular biological methods, and DNA sequences and mutations were compared with published data. The protein expression of Bcl10 and nuclear factor kappaB (NF-κB) were detected with immunohistological and immunofluorescence colocalization. Bcl10 gene expression was detected in 15 OAL cases. Novel mutations were found in 11 cases. Notably, 1 mutation, which matched a published mutation, was detected in 1 ALH case; 1 novel mutation was found in 1 RLH case; and no Bcl10 gene mutation was found in controls. Most novel mutations were truncation mutations, resulting in a truncated protein product of 99 amino acids (compared to the full-length 233 amino acids; GenBank accession No. EF189176). Results of tests for abnormal Bcl10 gene expression in nuclei or cytoplasm were consistent with changes in NF-κB translocation. This report is the first of newly discovered mutations in the Bcl10 gene in the Chinese population. The distribution of the mutations is consistent with and more sensitive than that of the pathological diagnosis. These mutations can be used to identify the stage and clinical characteristics even when morphological changes are absent.

Hepatic mesenchymal hamartoma in a neonate with a Bochdalek diaphragmatic hernia: A case report

The Bochdalek diaphragmatic hernia (BDH) is a common birth defect that is associated with other congenital malformations. Hepatic mesenchymal hamartoma (HMH) is the second most common benign hepatic tumor in children. The association between BDH and HMH or ectopic hepatic tissue is uncommon. We report a case of a female newborn with a left BDH that at surgery was incidentally found to have a tumor of 3.5cm in maximum dimension with a serous muscular membrane. The histopathological study revealed vascular–mesenchymal stroma with bile ducts entrapped and peripheral normal hepatic tissue. These findings correlate with the diagnosis of hepatic mesenchymal hamartoma (HMH) in ectopic hepatic tissue. Our objective is to report a case of a rare association between HMH and BDH as well as discuss its differential diagnosis.

DIAGNOSTIC YIELD OF SURAL NERVE BIOPSY, A RETROSPECTIVE ANALYSIS OF 10 YEARS DATA

MethodReports of sural nerve biopsies, done between period of January 2000 and March 2010 at Neuropathology Department of Frenchay Hospital were analysed retrospectively.ResultsThe total number of biopsies was 194. 111...

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient