bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Aurora‐A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation
Authors: Pan Jennifer Y. , Ajani Jaffer A. , Gu Jian , Gong Yubo , Quin Angel , Hung Maosheng , Wu Xifeng , Izzo Julie G.
Published: December 2011

BACKGROUND:

Aurora‐A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation.

METHODS:

Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease‐free survival (DFS) and median survival time (MTS).

RESULTS:

All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12‐8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin‐based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01‐5.17; P = .048) and MTS (P = .026). The variant 91A‐169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15‐5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00‐7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28‐17.11; P = <.001), and was associated significantly shorter DFS (P = .003).

CONCLUSIONS:

Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy‐resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. Cancer 2012. © 2011 American Cancer Society.
A double‐blind, randomized, placebo‐controlled, phase 2 study of maintenance enzastaurin with 5‐fluorouracil/leucovorin plus bevacizumab after first‐line therapy for metastatic colorectal cancer
Authors: Wolff Robert A. , Fuchs Martin , Di Bartolomeo Maria , Hossain Anwar M. , Stoffregen Clemens , Nicol Steven , Heinemann Volker
Published: December 2011

BACKGROUND:

Enzastaurin and bevacizumab have demonstrated synergistic antitumor effects and, in phase 1 studies, the combination was well tolerated. This phase 2 study assessed enzastaurin with 5‐fluorouracil/leucovorin plus bevacizumab as maintenance therapy for metastatic colorectal cancer (MCRC).

METHODS:

Patients with locally advanced or MCRC and stable or responding disease after completing 6 cycles of first‐line chemotherapy randomly received a loading dose of enzastaurin 1125 mg, followed by 500 mg/d subsequent doses or placebo. Both arms received 5‐fluorouracil/leucovorin (leucovorin 400 mg/m2 intravenously [IV], 5‐fluorouracil 400‐mg/m2 bolus, 5‐fluorouracil 2400 mg/m2 IV) plus bevacizumab 5 mg/kg IV, every 2 weeks. The primary endpoint was progression‐free survival (PFS), from randomization. Overall survival (OS) and PFS were also assessed from start of first‐line therapy. Enrollment was stopped, and the final analysis was conducted after 73 PFS events.

RESULTS:

Fifty‐eight patients were randomized to enzastaurin and 59 to placebo. For the enzastaurin and placebo arms, respectively, the median cycles received were 9 and 10, and the median PFS was 5.8 and 8.1 months (hazard ratio [HR], 1.35; 95% confidence interval [CI], 0.84‐2.16; P = .896). Median OS was not calculable because of high censoring (77.6% enzastaurin; 91.5% placebo). The median PFS from start of first‐line therapy was 8.9 months for enzastaurin and 11.3 months for placebo (HR, 1.39; 95% CI, 0.86‐2.23; P = .913). More enzastaurin patients developed thrombosis or embolism compared with placebo (15.8% and 1.7%; P = .008). One possibly enzastaurin‐related death occurred because of arrhythmia.

CONCLUSIONS:

Enzastaurin combined with bevacizumab‐based therapy is tolerable, but does not improve PFS during maintenance therapy in patients with MCRC compared with bevacizumab‐based therapy alone. Cancer 2012. © 2011 American Cancer Society.
Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis
Authors: Buscariollo Daniela L. , Park Henry S. , Roberts Kenneth B. , Yu James B.
Published: December 2011

BACKGROUND:

Atypical teratoid rhabdoid tumor (ATRT) is a rare central nervous system malignancy with a poor prognosis that affects mostly young children. Although radiotherapy (RT) historically has been delayed in patients aged <3 years, emerging evidence suggests a role for RT to achieve long‐term survivorship. Clinical features and age‐dependent trends of RT use were evaluated for patients with ATRT.

METHODS:

The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify 144 patients with ATRT from 1973 to 2008. The primary endpoint was median overall survival (OS). Clinical and treatment variables were assessed for an association with OS using Cox proportional hazards models. Landmark analysis was used to correct for immortal time bias of adjuvant RT.

RESULTS:

The median age at diagnosis was 1 year (range, 0‐67 years). Gross total resection of the primary tumor was achieved in 39% of patients, and 33% of patients received RT. From 1992 to 2008, RT use increased 2.4‐fold in patients aged ≤3 years. The median OS for was 10 months. In multivariate analyses, metastatic disease (hazard ratio, 2.83; 95% confidence interval, 1.53‐5.23; P = .001) and RT (hazard ratio, 0.10; 95% confidence interval, 0.01‐0.73; P = .02) were identified as independent predictors of survival. Landmark analysis confirmed a robust association between RT use and survival, which was attenuated in patients ages 4 to 17 years compared with younger patients.

CONCLUSIONS:

The current results indicated that RT may offer a significant survival benefit for patients with ATRT and that patients aged ≤3 years may derive more benefit from initial RT compared with older children. The authors concluded that prospective clinical trials are needed to examine the role of RT in the initial management of ATRT in patients aged <3 years. Cancer 2012. © 2011 American Cancer Society.
A method for analyzing the business case for provider participation in the National Cancer Institute's Community Clinical Oncology Program and similar federally funded, provider‐based research networks
Authors: Reiter Kristin L. , Song Paula H. , Minasian Lori , Good Marjorie , Weiner Bryan J. , McAlearney Ann Scheck
Published: December 2011

BACKGROUND:

The Community Clinical Oncology Program (CCOP) plays an essential role in the efforts of the National Cancer Institute (NCI) to increase enrollment in clinical trials. Currently, there is little practical guidance in the literature to assist provider organizations in analyzing the return on investment (ROI), or business case, for establishing and operating a provider‐based research network (PBRN) such as the CCOP. In this article, the authors present a conceptual model of the business case for PBRN participation, a spreadsheet‐based tool and advice for evaluating the business case for provider participation in a CCOP organization.

METHODS:

A comparative, case‐study approach was used to identify key components of the business case for hospitals attempting to support a CCOP research infrastructure. Semistructured interviews were conducted with providers and administrators. Key themes were identified and used to develop the financial analysis tool.

RESULTS:

Key components of the business case included CCOP start‐up costs, direct revenue from the NCI CCOP grant, direct expenses required to maintain the CCOP research infrastructure, and incidental benefits, most notably downstream revenues from CCOP patients. The authors recognized the value of incidental benefits as an important contributor to the business case for CCOP participation; however, currently, this component is not calculated.

CONCLUSIONS:

The current results indicated that providing a method for documenting the business case for CCOP or other PBRN involvement will contribute to the long‐term sustainability and expansion of these programs by improving providers' understanding of the financial implications of participation. Cancer 2012. © 2011 American Cancer Society.
Developmental changes of rhesus monkeys in response to separation from the mother
Authors: Zhang Bo , Suarez‐Jimenez Benjamin , Hathaway Amanda , Waters Carlos , Vaughan Kelli , Noble Pamela L. , Fox Nathan A. , Suomi Stephen J. , Pine Daniel S. , Nelson Eric E.
Published: December 2011

The development of separation response behaviors in infant rhesus macaques across the first 6 months of life was assessed. Seventeen infants underwent a neonatal assessment at 7, 14, 21, and 30 days of age which included a brief period of social isolation. At 3 and 6 months of age these same monkeys and four additional subjects were again subjected to a period of brief social isolation and also exposed to a novel environment with their sedated mother. Results indicate a developmental increase followed by a steady decline in the frequency of separation vocalizations. A modest relationship between early‐infancy locomotor profiles and separation responses was also observed at several time points suggesting a possible relationship between these measures. However, stable inter‐individual measures of separation distress did not emerge until late in the infantile period. This could suggest that high levels of maternal contact‐seeking behavior early in infancy are context specific and not a reliable index of enduring temperament. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 798–807, 2012
Respiratory sinus arrhythmia: A marker for positive social functioning and receptive language skills in children with autism spectrum disorders
Authors: Patriquin Michelle A. , Scarpa Angela , Friedman Bruce H. , Porges Stephen W.
Published: December 2011

The current study builds on the emerging autism spectrum disorder (ASD) literature that associates autonomic nervous system activity with social function, and examines the link between respiratory sinus arrhythmia (RSA) and both social behavior and cognitive function. The RSA response pattern was assessed in 23 4‐ to 7‐year‐old children diagnosed with an ASD. Higher baseline RSA amplitudes were associated with better social behavior (i.e., more conventional gestures, more instances of joint attention) and receptive language abilities. Similar to reports of typically developing children, ASD children with higher RSA amplitude at baseline showed greater RSA and HP reactivity during an attention‐demanding task. These results highlight the importance of studying RSA as a marker of positive function in children with ASD. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 55: 101–112, 2013
“Allorestriction” should be distinguished from “alloreactivity”
Authors: Cohn Melvin
Published: December 2011

Whether or not allorestriction should be distinguished from alloreactivity depends on one's model of the TCR–ligand interaction. If the ligand is viewed as a determinant formed by a meld between peptide and the MHC‐encoded restricting element, then the TCR, like the BCR, has a single combining site specific for the composite epitope (the Centric Model). If, however, one views the recognition of peptide and the MHC‐encoded restricting element as independent, then interactions at two sites of the TCR must be integrated to signal the T cell (the Tritope Model). As TCR recognition of the MHC‐encoded restricting element is, by definition, restricted (allele‐specific), then under the Centric Model, all TCR signaling interactions with the composite epitope are due to allorestriction, which is peptide‐specific. In contrast, under the Tritope Model, there are two classes of signaling interaction, allorestriction and alloreactivity. Alloreactivity is peptide‐unspecific and is triggered by recognition of the allo‐MHC‐encoded restricting element allele. Alloreactivity is incompatible with the Centric Model, under which one would predict that it does not exist. Selected data are analyzed to illustrate the importance of this distinction.
Studies on the Diastereoselective Intramolecular Pauson–Khand Reaction on Regioisomeric Chiral Perhydrobenzoxazines Derived from (–)‐8‐Aminomenthol
Authors: Maestro Alicia , Pedrosa Rafael , Pérez‐Encabo Alfonso , Pérez‐Rueda Juan J.
Published: December 2011

Chiral perhydrobenzoxazines derived from (–)‐8‐aminomenthol and containing a 1,6‐enyne moiety participate in intramolecular diastereoselective Pauson–Khand reactions with diastereoselection that depends on the nature of the starting compounds. 3‐Propargyl‐2‐vinyl‐substituted perhydrobenzoxazines yielded the cyclization products with low diastereoselectivity except for compounds where the double bond was 1,2‐disubstituted. Regioisomeric perhydrobenzoxazines with the acetylenic bond at C‐2 and an allyl substituent at the nitrogen atom gave much better stereochemical discrimination.
Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis
Authors: Pellicoro Antonella , Aucott Rebecca L. , Ramachandran Prakash , Robson Andrew J. , Fallowfield Jonathan A. , Snowdon Victoria K. , Hartland Stephen N. , Vernon Madeleine , Duffield Jeremy S. , Benyon Christopher R. , Forbes Stuart J. , Iredale John P.
Published: December 2011

Elastin has been linked to maturity of liver fibrosis. To date, the regulation of elastin secretion and its degradation in liver fibrosis has not been characterized. The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP-12) in its turnover during fibrosis. Liver fibrosis was induced by either intraperitoneal injections of carbon tetrachloride (CCl4) for up to 12 weeks (rat and mouse) or oral administration of thioacetamide (TAA) for 1 year (mouse). Elastin synthesis, deposition, and degradation were investigated by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blotting, and casein zymography. The regulation of MMP-12 elastin degradation was defined mechanistically using CD11b-DTR and MMP-12 knockout mice. In a CCl4 model of fibrosis in rat, elastin deposition was significantly increased only in advanced fibrosis. Tropoelastin expression increased with duration of injury. MMP-12 protein levels were only modestly changed and in coimmunoprecipitation experiments MMP-12 was bound in greater quantities to its inhibitor TIMP-1 in advanced versus early fibrosis. Immunohistochemistry and macrophage depletion experiments indicated that macrophages were the sole source of MMP-12. Exposure of CCl4 in MMP-12−/− mice led to a similar degree of overall fibrosis compared to wildtype (WT) but increased perisinusoidal elastin. Conversely, oral administration of TAA caused both higher elastin accumulation and higher fibrosis in MMP-12−/− mice compared with WT.

Conclusion:

Elastin is regulated at the level of degradation during liver fibrosis. Macrophage-derived MMP-12 regulates elastin degradation even in progressive experimental liver fibrosis. These observations have important implications for the design of antifibrotic therapies.
An extension of the grid empowered molecular simulator to quantum reactive scattering
Authors: Rampino Sergio , Faginas Lago Noelia , Laganà Antonio , Huarte‐Larrañaga Fermin
Published: December 2011

Within the activities of the D37 COST Action, we have further developed the quantum dynamics framework of the grid empowered molecular simulator (GEMS) implemented on the segment of the European grid available to the COMPCHEM (computational chemistry) virtual organization. GEMS does now include in a full ab initio approach, the evaluation of the detailed quantum (both time dependent and time independent) dynamics of small systems starting from the calculation of the electronic structure properties as well as the direct calculation of thermalized properties. Illustrative, full dimensional applications of the extended simulator to the H + H2, N + N2, and O + O2 systems are presented. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
In vivo degradation and new bone formation of calcium phosphate cement–gelatin powder composite related to macroporosity after in situ gelatin degradation
Authors: Kasuya Akihiro , Sobajima Satoshi , Kinoshita Mitsuo
Published: December 2011

Calcium phosphate cement (CPC) is reported to have excellent biocompatibility and osteoconductivity. However, its biodegradability must be improved to promote bone regeneration. We have mixed gelatin powder with CPC to create a composite containing macropores with interconnectivity. Sixty rabbits were grouped as follows: 85wt% CPC to 15wt% gelatin powder (C15), 90wt% CPC to 10wt% gelatin powder (C10), 100wt% CPC (C0) as control group and Sham group. Trabecular bone defects of distal femurs were made and implanted with the composites. The femurs were harvested for histomorphometry at 4, 12, 24 weeks after implantation, and mechanical testing at 3 days, 1, 4, 12, 24 weeks. Compared with C0, X‐ray and micro‐CT results of the composites revealed a progressive increase in the amount of CPC–gelatin powder composite which was replaced by trabeculae. New bone area increased from 3.8 to 18% in C10, and 4.2 to 22% in C15, residual composite area decreased from 65 to 31% in C10, and 70 to 20% in C15. The compressive strength of C15 was 9.2 MPa, which was inferior to 14.6 MPa (normal cancellous bone), but was 27.4 MPa in C10 at 1 week. Further improvement of this composite may make a suitable scaffold for bone regeneration. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1103–1111, 2012
Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma
Authors: Shen Aidong , Zhang Yunqing , Yang Huiguang , Xu Ruisheng , Huang Guowei
Published: December 2011

Background

This study aimed to investigate the expression of ZEB1 in osteosarcoma tissues and to discuss the relationship between ZEB1 expression and osteosarcoma metastasis.

Methods

Using RT‐PCR and Western blotting, the mRNA and protein expressions of ZEB1 in the osteosarcoma and normal bone tissues were detected. Using the RNA interference technique, the expression of ZEB1 in the human osteosarcoma MG‐63 cell line was downregulated, and the changes in the invasion of MG‐63 cells were examined.

Results

The positive mRNA expression rate of ZEB1 in the osteosarcoma tissues was significantly higher than that in normal bone tissue (P < 0.05). The protein expression level of ZEB1 in the sarcoma tissues from patients with positive lung metastasis was significantly higher than that from patients without lung metastasis (P < 0.05). After the transfection of ZEB1 siRNA into the MG‐63 cells, the protein expression of ZEB1 was significantly reduced (P < 0.05), and the number of cells that passed through the Transwell chamber was significantly lower than that in the non‐transfected control group as well as the transfected control group (P < 0.05).

Conclusions

The overexpression of ZEB1 in osteosarcoma may be related to the carcinogenesis and development as well as metastasis and invasion of osteosarcoma. J. Surg. Oncol. 2012; 105:830–834. © 2011 Wiley Periodicals, Inc.
Expression patterns of endothelin‐1 and its receptors in colorectal cancer
Authors: Liakou Paraskevi , Tepetes Kostantinos , Germenis Anastasios , Leventaki Vasiliki , Atsaves Vassilis , Patsouris Efstratios , Roidis Nikolaos , Hatzitheophilou Konstantinos , Rassidakis George Z.
Published: December 2011

Background and Objectives

Endothelin‐1 (ET‐1), a potent vasoconstricting peptide, plays an important role in carcinogenesis. Previous in vitro studies have shown that colorectal cancer cells produce ET‐1.

Methods

ET‐1 and its receptors ET‐A (ETAR) and ET‐B (ETBR) were analyzed in colorectal cancer cell lines and tumors by Western blot and immunohistochemistry. Also, ET‐1 levels were measured by ELISA in blood samples collected before and after tumor resection.

Results

ET‐1 was immunohistochemically expressed by tumor cells at a variable level in 39 cases tested. The adjacent normal mucosa was negative for ET‐1 expression. Strong ETAR expression observed in the deeper infiltrating areas at the periphery of neoplastic tissue correlated significantly with tumor stage. ETBR levels were very low or undetectable. Western blot analysis in paired (normal, tumor) fresh‐frozen samples of colorectal cancers and in four colon carcinoma cell lines confirmed these findings. In addition, lower levels of ET‐1 in the peripheral circulation after the tumor resection were found by ELISA as compared to those observed before surgery.

Conclusions

ET‐1 and ETAR, but not ETBR, are expressed at a higher level in primary and cultured colon carcinoma cells as compared to normal colon mucosa cells. Further functional studies are needed to explore the role of ET‐1/ETAR axis in colon carcinogenesis. J. Surg. Oncol. 2012; 105:643–649. © 2011 Wiley Periodicals, Inc.
Routine prophylactic sentinel lymph node biopsy is not indicated in women undergoing prophylactic mastectomy
Authors: Czyszczon Irene Alina , Roland Lane , Sahoo Sunati
Published: December 2011

Background

Prophylactic mastectomies (PM) are performed to reduce the risk of breast cancer. Occasionally an occult carcinoma is found in PM specimens. Given the high morbidity of axillary lymph node dissection (ALND), some perform prophylactic sentinel lymph node biopsy (SLNB). We undertook a study to examine if prophylactic SLNB is indicated in all patients undergoing PM.

Methods

A retrospective review of all PM between 2004 and 2010 was performed. The stage of tumor on the disease side and the pathologic findings in the prophylactic breast were analyzed. The number of SLN and the frequency of lymph node metastases were evaluated.

Results

A total of 199 PM on 184 patients were performed: 169 contralateral PM and 30 bilateral PM. Of the 199 PM, 12 had occult carcinomas (6.0%): 10 non‐invasive, 1 microinvasive and 1 T1b invasive tumor. 153 of 199 PM specimens had prophylactic SLNB, of which only 2 had a positive SLN that originated from the index side of the breast.

Conclusions

Although it is not uncommon to find occult carcinomas in the prophylactic breast, it is rare for the occult carcinoma to spread to the lymph nodes. Therefore, routine prophylactic SLNB is not indicated in patients undergoing PM. J. Surg. Oncol. 2012; 105:650–654. © 2011 Wiley Periodicals, Inc.
Epithelial–mesenchymal transition and mesenchymal–epithelial transition via regulation of ZEB‐1 and ZEB‐2 expression in pancreatic cancer
Authors: Kurahara Hiroshi , Takao Sonshin , Maemura Kosei , Mataki Yuko , Kuwahata Taisaku , Maeda Koki , Ding Qiang , Sakoda Masahiko , Iino Satoshi , Ishigami Sumiya , Ueno Shinichi , Shinchi Hiroyuki , Natsugoe Shoji
Published: December 2011

Background and Objecties

Phenotypic plasticity of cancer cells via epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) is essential for tumor progression and metastasis.

Methods

Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E‐cadherin, vimentin, ZEB‐1, and ZEB‐2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E‐cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm.

Results

High expressions of ZEB‐1 and ZEB‐2 in the primary tumors were significantly associated with repression of E‐cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty‐three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E‐cadherin showed high E‐cadherin expression. Cancer cells in the larger metastases showed high expression of E‐cadherin (P = 0.0061) and low expression of ZEB‐1 (P = 0.0170) and ZEB‐2 (P = 0.0036) compared with those in the smaller metastases.

Conclusions

In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB‐1 and ZEB‐2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively. J. Surg. Oncol. 2012; 105:655–661. © 2011 Wiley Periodicals, Inc.
Composite biological reconstruction following total calcanectomy of primary calcaneal tumors
Authors: Li Jing , Wang Zhen , Guo Zheng , Yang Ming , Chen Guojing , Pei Guoxian
Published: December 2011

Background

Advances in oncologic treatment modalities and wide resection have made limb salvage procedures in calcaneal malignancy or aggressive benign tumor increasingly possible. However, reconstructions of the calcaneus remain a major surgical challenge because of the rarity and specific anatomy of this condition.

Methods

we retrospectively reviewed 4 patients who had primary calcaneal tumors and underwent total calcanectomy and reconstructions with use of composite of allograft and vascularized osteocutaneous fibular grafts between 2007 and 2010. The diagnoses included chondrosarcoma in 1, fibrosarcoma in 1, aggressive osteoblastoma in 1, and giant‐cell tumor in 1. Wide resection margins were achieved in all patients. The mean age at the time of the operation was 32.1 years. Patients were examined clinically and radiographically and were assessed functionally with Musculoskeletal Tumor Society (MSTS) score and American Orthopaedic Foot and Ankle Society (AOFAS) score.

Results

The median duration of follow‐up was 24.5 months. No local recurrence occurred in this series and all patients had no evidence of disease at the time of final follow‐up. Limb salvage was achieved in all patients. Revision surgery was necessary in two patients because of complications (skin flap necrosis and infection). The average MSTS 93 score and AOFAS score were 91.7% and 87.5 at the final follow‐up, respectively. All fibular flaps survived and bone unions achieved successfully. The overall mean time for bone union was 9.5 months. The mean time to full‐weight bearing was 7 months.

Conclusions

Vascularized fibular flaps in combination with massive allografts provide an excellent option for biological reconstruction after total calcanectomy in tumor situation and have proven to be a successful limb salvage procedure, which result in earlier patient recovery and return of function.

Level of Evidence

Therapeutic Level IV. J. Surg. Oncol. 2012; 105:673–678. © 2011 Wiley Periodicals, Inc.
Clinicopathological prognostic factors of superficial non‐small round cell soft tissue sarcomas
Authors: Tsukushi Satoshi , Nishida Yoshihiro , Shido Yoji , Wasa Junji , Ishiguro Naoki
Published: December 2011

Background

We undertook this study to assess the therapeutic results of superficial soft tissue sarcomas as related to the presence of microscopic invasion, and to identify prognostic factors so as to optimize the therapeutic strategy.

Methods

From 1995 to 2008, 105 patients who were treated surgically for superficial non‐small round cell soft tissue sarcoma were investigated with regard to clinical results and microscopic invasion, and the influence exerted on prognosis was analyzed. We analyzed overall, metastasis‐free, and local recurrence‐free survival rates and determined the difference in survivorship between with and without fascia invasion.

Results

The 5‐year overall survival rate and 5‐year disease‐free survival rate were 95.3% and 81.8%. For overall survival, age (P < 0.05), grade (P < 0.05), tumor size (P < 0.05), and fascial invasion (P < 0.0001) were significant unfavorable prognostic factors, while for metastasis‐free survival, grade (P < 0.01) and fascial invasion (P < 0.001) were significant unfavorable prognostic factors. For local recurrence‐free survival, fascial invasion alone (P < 0.01) was a significant unfavorable prognostic factor.

Conclusions

Fascial invasion on pathological examination of resected specimens was identified as a significant unfavorable prognostic factor. Selecting the postoperative adjuvant therapy based on a detailed evaluation of any fascial invasion is an important part of the therapeutic strategy. J. Surg. Oncol. 2012; 105:668–672. © 2011 Wiley Periodicals, Inc.
Analysis of glycoforms on the glycosylation site and the glycans in monoclonal antibody biopharmaceuticals
Authors: Uçaktürk Ebru
Published: December 2011

Therapeutic monoclonal antibodies (mAbs), immunoglobulins, have been efficiently used in the treatment of many diseases, such as cancer, inflammatory and cardiovascular diseases, and organ transplantation. mAbs are glycoprotein molecules undergoing posttranslational modifications. Glycosylation is one of the posttranslational modifications. Different glycoforms that are important for maintaining the potency of mAb drugs show various biological activities. Therefore, the profile of the glycans and glycosylation sites should be determined to produce safe, good quality, consistent mAb drugs for human use. For this reason, simple, robust, accurate, and reproducible analytical methods need to be developed. In this article, chromatographic methods for the analysis of the glycoforms on the glycosylation site and the glycans in mAb biopharmaceuticals have been evaluated.
Self‐Healing Supramolecular Polymers In Action
Authors: van Gemert Gaby M. L. , Peeters Joris W. , Söntjens Serge H. M. , Janssen Henk M. , Bosman Anton W.
Published: December 2011

Sophisticated polymeric materials with “responsive” properties, such as self‐healing, are beginning to reach the market. Supramolecular polymers, i.e., polymers that owe their mechanical properties primarily to the reversible, non‐covalent interactions, such as hydrogen bonding interactions, between the macromolecules, have frequently been employed as self‐healing materials. The quadruple hydrogen bonding ureidopyrimidinone (UPy) unit is a particularly effective and versatile design motif, since it forms very strong but reversible linkages, and can be incorporated into virtually any type of polymer backbone, leading to materials with increased mechanical properties. Supramolecular polymers are presented, with an emphasis on those based on the UPy‐unit, and their use in self‐healing applications is highlighted and discussed.
Decreased expression of WWOX in the development of esophageal squamous cell carcinoma
Authors: Guo Wei , Wang Guiying , Dong Yuran , Guo Yanli , Kuang Gang , Dong Zhiming
Published: December 2011

The WW domain‐containing oxidoreductase (WWOX) gene, located on chromosome 16q23.3–24.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various carcinomas. The present study was to investigate the alterations of WWOX expression and its correlation with polymorphism, the level of WWOX loss of heterozygosity (LOH), and methylation status in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry and RT‐PCR methods were used, respectively, to examine the protein and mRNA expression of WWOX in ESCC tissues. PCR‐RFLP, PCR‐SSLP, and MSP approach were used, respectively, to detect polymorphisms of rs3764340, rs2548861, and rs1079635 site, the level of LOH, and WWOX methylation status. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC. Protein and mRNA expression of WWOX was reduced in ESCC tumor tissues and was associated with LOH and hypermethylation of the gene. The G allele of rs3764340 significantly elevated the risk of developing ESCC and was associated with TNM stage. LOH at the WWOX loci was observed in 41.4% tumors. The hypermethylation of promoter and exon1 of WWOX was found to be occurred in dysplastic tissues and the methylation frequency of WWOX in ESCC tumor tissues was significantly higher than that in corresponding normal tissues and was associated with UGIC family history. In all, these results indicate that the WWOX gene may play an important role in the development of ESCC especially in individuals with UGIC family history. © 2011 Wiley Periodicals, Inc.
Overexpression of small GTPases directly correlates with expression of δ‐catenin and their coexpression predicts a poor clinical outcome in nonsmall cell lung cancer
Authors: Zhang Jun‐Yi , Zhang Di , Wang En‐Hua
Published: December 2011

δ‐catenin can affect cytoskeletal assembly, and promote cell migration by regulating the activity of small GTPases. While many malignancies have been shown to be positive for δ‐catenin, it is still unclear whether δ‐catenin and small GTPases are coexpressed in tumor cells, and so is the relationship between their coexpression and prognosis in the tumor patients. In this study, immunohistochemistry was performed to examine expressive levels of δ‐catenin, cdc42, and Rac1 in 135 cases of nonsmall cell lung cancer (NSCLC), including 60 cases with follow‐up records. Thirty samples of paired lung cancer tissues and adjacent normal lung tissues were collected to analyze mRNA and protein expression of δ‐catenin and small GTPases. The effects of δ‐catenin on small GTPases expression and invasive ability of lung cancer cells were also evaluated. Compared with normal lung tissues, both mRNA and protein levels of δ‐catenin and small GTPases were increased in lung cancer tissues (P < 0.05), and the expression of small GTPases directly correlated with that of δ‐catenin (P < 0.001). In addition, δ‐catenin and small GTPases tended to be coexpressed in lung adenocarcinoma, advanced stages, and primary tumors with lymph node metastasis (all P < 0.05). The patients with coexpression of δ‐catenin and small GTPases had a shorter survival time than those without coexpression (P < 0.05). Furthermore, δ‐catenin overexpression could enhance invasive ability of lung cancer cells by upregulating protein and transcriptional level of small GTPases. Therefore, δ‐catenin likely upregulates the activity of small GTPases at transcriptional level, and their coexpression may predict a poor clinical outcome in NSCLC patients. © 2011 Wiley Periodicals, Inc.
An Advanced Group Contribution Method for High‐Dimensional, Sparse Data Sets
Authors: Lee Chang Jun , Lee Jong Min
Published: December 2011

Today’s chemical processes involve many components, and it is necessary to know their basic physical properties for process design and operation. However, it is not always possible to find the property information of all components in the literature. Generally, there are two ways to evaluate properties of chemical compounds when they do not exist in the literature: the experimental measurement and predictive approaches based on empirical models. The latter is called the group contribution method (GCM), and its basic concept is that specific functional groups or fragments of a molecule contribute to the value of its physical property. The advantage of the GCMs is that they reduce the effort and cost compared to experiments. This study proposes a novel GCM method suitable for high‐dimensional, sparse data sets. In order to improve its applicability and accuracy, the database is extended and divided into non‐ring group compounds and ring group ones. Support vector regression (SVR) is adopted as the regression model, and a derivative‐free optimization approach, referred to as particle swarm optimization, is incorporated into the parameter optimization step in learning the SVM model to avoid local optimality. Performance of the proposed model is compared to those of other GCMs.
Evaluation of a MR‐quadrupole imaging coil for spinal interventions in a vertical 1.0 T MRI
Authors: Rump Jens C. , Streitparth Florian , Böning Georg , Seebauer Christian J. , Walter Thula , Güttler Felix , Hamm Bernd , Teichgräber Ulf K. M.
Published: December 2011

The in vivo pain treatment was successfully performed with the patient in a prone position. The PD‐weighted TSE with echo time = 10 ms rendered contrast‐to‐noise‐ratio values of 27 ± 10 for needle/fat, 1.6 ± 5 for needle/muscle, and 4 ± 4.7 for needle/nerve tissue. The mean diameter of the needle artifact was 1.2 ± 0.2 mm. In the T1‐weighted gradient echo, the needle's artifact diameter was 6 ± 2 mm; the needle's contrast‐to‐noise ratio relative to muscle tissue was 4 ± 2, 7.6 ± 1.5 for needle/fat, and 5 ± 1 for needle/nerve tissue. With the PD‐weighted TSE (echo time = 10 ms) and the T1‐weighted gradient echo, the needle was imaged reliably throughout the intervention. The butterfly surface coil is feasible for the guidance of spinal interventions in a prone patient. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Distortion correction in EPI at ultra‐high‐field MRI using PSF mapping with optimal combination of shift detection dimension
Authors: Oh Se‐Hong , Chung Jun‐Young , In Myung‐Ho , Zaitsev Maxim , Kim Young‐Bo , Speck Oliver , Cho Zang‐Hee
Published: December 2011

Despite its wide use, echo‐planar imaging (EPI) suffers from geometric distortions due to off‐resonance effects, i.e., strong magnetic field inhomogeneity and susceptibility. This article reports a novel method for correcting the distortions observed in EPI acquired at ultra‐high‐field such as 7 T. Point spread function (PSF) mapping methods have been proposed for correcting the distortions in EPI. The PSF shift map can be derived either along the nondistorted or the distorted coordinates. Along the nondistorted coordinates more information about compressed areas is present but it is prone to PSF‐ghosting artifacts induced by large k‐space shift in PSF encoding direction. In contrast, shift maps along the distorted coordinates contain more information in stretched areas and are more robust against PSF‐ghosting. In ultra‐high‐field MRI, an EPI contains both compressed and stretched regions depending on the B0 field inhomogeneity and local susceptibility. In this study, we present a new geometric distortion correction scheme, which selectively applies the shift map with more information content. We propose a PSF‐ghost elimination method to generate an artifact‐free pixel shift map along nondistorted coordinates. The proposed method can correct the effects of the local magnetic field inhomogeneity induced by the susceptibility effects along with the PSF‐ghost artifact cancellation. We have experimentally demonstrated the advantages of the proposed method in EPI data acquisitions in phantom and human brain using 7‐T MRI. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Thermomechanical and electrical characterization of epoxy‐organoclay nanocomposites
Authors: Thelakkadan A.S. , Coletti G. , Guastavino F. , Fina A.
Published: December 2011

The effect of amount of clay content on the thermomechanical and electrical properties of epoxy/organoclay nanocomposites is investigated in the present research. An organoclay, cloisite 30B (C30B), was dispersed in the epoxy resin and was cured with an amine curing agent. The morphology of the nanocomposite examined by X‐ray diffraction shows exfoliation for nanocomposites with lesser clay content and intercalation for nanocomposites with higher clay content. The storage modulus (E′) of the nanocomposites increases monotonously with the increase in the amount of clay. The short time alternating current breakdown strength of the nanocomposites increases by the addition of C30B up to a certain clay content and then show a decrease. The space charge measured by pulsed electroacoustic method shows that the nanocomposite accumulate a very less amount of space charge and the charge decay in the nanocomposites are quicker than in the pure polymer. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
What Project Strategy Really Is: The Fundamental Building Block in Strategic Project Management
Authors: Patanakul Peerasit , Shenhar Aaron J.
Published: December 2011

Strategic project management is gradually becoming a popular and growing trend within the discipline of project management. The general idea is that project management teams must learn how to deal with the business aspects of their projects, as well as better support their company's business strategy and sustainability, rather than just focus on meeting traditional time, budget, and performance goals. Although this approach has been gaining popularity, strategic project management has not yet become an explicit and widely used approach in the practice of project implementation. One of the concepts mentioned as an important element is project strategy; however, no universal framework or even a clear definition of what project strategy is has so far emerged. The goal of this article is to fill in this gap and provide a useful definition and a framework for the further study and implementation of the project strategy concept. Specifically, to achieve this goal, we first look at the origins of strategy in military and business research to discuss the question of what, exactly, project strategy is; we follow this discussion with an explicit definition of a project strategy. We then outline a framework for building a dedicated project strategy document for an individual project, and show how this framework can guide the project planning and execution processes. Using a case study approach, which included an action research phase, we demonstrate how project teams can adopt the strategy concept in a natural way that would lead their project to better business results.
Knowledge Acquisition Using Psychotherapy Technique for Critical Factors Influencing Construction Project Layout Planning
Authors: Abdul-Rahman Hamzah , Wang Chen , Siong Eng Khe
Published: December 2011

The positioning of equipment on a construction site may change in different construction phases, different environments, and different types of end products, which greatly influence the decision of the site planning engineer who seeks to maximize the construction efficiency by minimizing the friction from the site layout. This study aims to acquire and analyze site planning experts' knowledge on critical factors influencing the construction layout planning using a psychotherapy technique. Through an open-structured interview survey and cluster analysis, 125 core factors influencing the site layout plan were analyzed and categorized into a database.
Adipokines: A treasure trove for the discovery of biomarkers for metabolic disorders
Authors: Lehr Stefan , Hartwig Sonja , Sell Henrike
Published: December 2011

Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion which may contribute to the development of metabolic diseases. Consequently, this correlation has emphasized the importance to further characterize the adipocyte secretion profile, and several attempts have been made to characterize the complex nature of the adipose tissue secretome by utilizing diverse proteomic profiling approaches. Although the entirety of human adipokines is still incompletely characterized, to date more than 600 potentially secretory proteins were identified providing a rich source to identify putative novel biomarkers associated with metabolic diseases.
A direct comparison of the diagnostic accuracy of three prostate cancer nomograms designed to predict the likelihood of a positive initial transrectal biopsy
Authors: Ouzaid Idir , Yates David R. , Hupertan Vincent , Mozer Pierre , Chartier‐Kastler Emmanuel , Haertig Alain , Bitker Marc‐Olivier , Rouprêt Morgan
Published: December 2011

BACKGROUND

Several tools have been developed to predict the outcome of prostate biopsies performed to diagnosis prostate cancer (PCa). However, few studies have focused on the comparative accuracy of these predictive tools. We aim to establish the predictive accuracy of three commonly used nomograms by comparing their prostate biopsy outcome predictions with actual pathological results.

METHODS

From January 2008 to December 2010, 708 consecutive patients with an elevated serum PSA level and/or abnormal DRE were referred to our institution. All data were collected prospectively. All patients underwent a TRUS 12‐core biopsy. Probability of a positive biopsy was predicted using three online risk calculation nomograms. The discriminative ability of the nomograms was assessed via AUC and the most accurate model was calibrated and compared to actual biopsy results.

RESULTS

Of 667 patients fulfilling all three nomograms criteria, 384 (57.5%) had PCa and 283 (42.5%) did not. AUC for the PCPT‐CRC, SWOP‐PRI, and Montreal nomograms was 0.68 (95% CI, 0.63–0.72), 0.72 (95% CI, 0.68–0.76), and 0.79 (95% CI, 0.76–0.82), respectively. A comparison of the three models' performance showed that the Montreal model provided the greatest predictive accuracy (P = 0.03).

CONCLUSIONS

External validation of three commonly used nomograms designed to predict the likelihood of a positive prostate biopsy reveals the Montreal model was more accurate than either the PCPT‐CRC or SWOP‐PRI models. The Montreal nomogram achieves a diagnostic accuracy of 79% and is superior to PSA alone though we await further research to define the probability (of cancer) threshold above which a prostate biopsy would be advised. Prostate 72:1200–1206, 2012. © 2011 Wiley Periodicals, Inc.
Altered association of interleukin‐6 with sex steroids in lipid metabolism disorder in men with prostate cancer receiving androgen deprivation therapy
Authors: Komatsu Shuichi , Hara Noboru , Ishizaki Fumio , Nishiyama Tsutomu , Takizawa Itsuhiro , Isahaya Etsuko , Kawasaki Takashi , Takahashi Kota
Published: December 2011

BACKGROUND

Interleukin‐6 produced in adipose tissue plays a role in lipid metabolism, and also interacts with sex steroids. This study was performed to elucidate the mechanism of lipid metabolism disorder during androgen deprivation therapy (ADT) in terms of the association of interleukin‐6 with sex steroids.

METHODS

Seventy‐two patients with localized prostate cancer were prospectively studied based on their body‐composition and blood samples before and after ADT for 6 months.

RESULTS

Before ADT, serum interleukin‐6 levels were inversely correlated with serum total‐testosterone (rs = −0.305, P = 0.009) and dihydrotestosterone (rs = −0.380, P = 0.006) concentrations, but not correlated with adrenal androgen or estradiol levels. Pretreatment interleukin‐6 levels were positively correlated with %body fat (rs = 0.349, P = 0.003) and %visceral fat (rs = 0.384, P = 0.001). After ADT, %body fat increased (P < 0.001) and lean body mass decreased (P = 0.036). After ADT, in contrast to the pretreatment relationship, interleukin‐6 levels were positively correlated with total‐testosterone concentrations (rs = 0.343, P = 0.003), and were positively correlated also with levels of androstenedione (rs = 0.351, P = 0.002) and estoradiol (rs = 0.335, P = 0.004). Interleukin‐6 levels were equivalent between before and after ADT (2.02 vs. 2.16 pg/ml, P = 0.205), but the positive correlation between interleukin‐6 levels and %body or %visceral fat noted before ADT disappeared after ADT.

CONCLUSIONS

Posttreatment interleukin‐6 levels had a strong positive correlation with total‐testosterone, androstenedione, and estradiol levels, suggesting that a regulation loop may emerge between these sex steroids and interleukin‐6 during ADT. The altered association between interleukin‐6 and sex steroids is possibly involved in ADT‐related lipid metabolism disorder with unchanged interleukin‐6 levels despite increased %body fat. Prostate 72:1207–1213, 2012. © 2011 Wiley Periodicals, Inc.