Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 32

Publication Record


AJCC eighth edition for soft tissue sarcoma of the extremities and trunk.
Cates JMM
(2018) Ann Oncol 29: 2023
MeSH Terms: Extremities, Humans, Neoplasm Staging, Sarcoma, Soft Tissue Neoplasms, United States
Added November 1, 2018
0 Communities
1 Members
0 Resources
6 MeSH Terms
Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.
Lewis WR, Malarkey EB, Tritschler D, Bower R, Pasek RC, Porath JD, Birket SE, Saunier S, Antignac C, Knowles MR, Leigh MW, Zariwala MA, Challa AK, Kesterson RA, Rowe SM, Drummond IA, Parant JM, Hildebrandt F, Porter ME, Yoder BK, Berbari NF
(2016) PLoS Genet 12: e1006220
MeSH Terms: Animals, Body Patterning, Cell Movement, Chlamydomonas, Cilia, Cytoskeleton, Disease Models, Animal, Extremities, Genetic Predisposition to Disease, Humans, Kartagener Syndrome, Mice, Microtubules, Mutation, Neural Tube, Proteins, Signal Transduction
Show Abstract · Added August 24, 2016
Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in mice demonstrated that this allele is likely pathogenic.
0 Communities
1 Members
0 Resources
17 MeSH Terms
A newborn with severe skeletal dysplasia.
Maalouf FI, Coggins SA, Phillips JA, Stefanescu BM, Weitkamp JH
(2016) Arch Dis Child Educ Pract Ed 101: 147
MeSH Terms: Bone Diseases, Developmental, Calcification, Physiologic, Extremities, Humans, Infant, Newborn, Male, Skull, Thorax, Treatment Outcome
Added October 16, 2015
0 Communities
1 Members
0 Resources
9 MeSH Terms
Medical malpractice and sarcoma care--a thirty-three year review of case resolutions, inciting factors, and at risk physician specialties surrounding a rare diagnosis.
Mesko NW, Mesko JL, Gaffney LM, Halpern JL, Schwartz HS, Holt GE
(2014) J Surg Oncol 110: 919-29
MeSH Terms: Delayed Diagnosis, Extremities, Humans, Malpractice, Physicians, Risk, Sarcoma
Show Abstract · Added January 20, 2015
BACKGROUND - We reviewed medico-legal cases related to extremity sarcoma malpractice in order to recognize those factors most commonly instigating sarcoma litigation.
METHODS - Over one million legal cases available in a national legal database were searched for malpractice verdicts and settlements involving extremity sarcoma spanning 1980-2012. We categorized verdict/settlement resolutions by state, year, award amount, nature of the complaint/injury, specialty of the physician defendant, and academic affiliation of defendant-amongst other variables.
RESULTS - Of the 216 cases identified, 57% of case resolutions favored the plaintiff, with a mean indemnity payment of $2.30 million (range $65,076-$12.66 million). Delay in diagnosis (81%), unnecessary amputation (11%), and misdiagnosis (7%) accounted for the majority of complaints. The greatest numbers of claims were filed against primary care specialties (34%), orthopaedic surgeons (23%), and radiologists (12%). Individual state tort reform measures were not protective against case resolution outcome.
CONCLUSIONS - Reported medico-legal claims involving sarcoma care continue to rise, with mean indemnity payments approaching 10 times that for other reported medical/surgical specialties. Primary care and orthopaedic specialties are the most commonly named physician defendants, citing a delay in diagnosis. This suggests further education in the front line diagnosis and management of sarcomas is needed.
© 2014 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
7 MeSH Terms
Racial Disparities in Extremity Soft-Tissue Sarcoma Outcomes: A Nationwide Analysis.
Alamanda VK, Song Y, Schwartz HS, Holt GE
(2015) Am J Clin Oncol 38: 595-9
MeSH Terms: Adult, African Americans, Age of Onset, Aged, Asian Americans, European Continental Ancestry Group, Extremities, Female, Health Status Disparities, Healthcare Disparities, Histiocytoma, Malignant Fibrous, Humans, Indians, North American, Inuits, Leiomyosarcoma, Liposarcoma, Male, Middle Aged, Multivariate Analysis, Oceanic Ancestry Group, Radiotherapy, SEER Program, Sarcoma, Survival Analysis, Tumor Burden, United States
Show Abstract · Added March 10, 2014
BACKGROUND - Racial disparities in access and survival have been reported in a variety of cancers. These issues, however, have yet to be explored in detail in patients with soft-tissue sarcomas (STS). The purpose of this paper was to investigate the independent role of race with respect to survival outcomes in STS.
METHODS - A total of 7601 patients were evaluated in this study. A SEER registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009 (n=7225) was performed. Survival outcomes were analyzed after patients were stratified by race. Multivariable survival models were used to identify independent predictors of sarcoma-specific death. The Wilcoxon rank-sum test was used to compare continuous variables. Statistical significance was maintained at P<0.05.
RESULTS - This study showed that African American patients were more likely to die of their STS. They were younger at presentation (P=0.001), had larger tumors (P<0.001), had less surgery (P=0.002), received radiotherapy less frequently (P=0.024), had higher family income (P<0.001), and were less likely to be married (P<0.001). African American race by itself was not an independent predictor of death.
CONCLUSIONS - African Americans encounter death due to STS at a much larger proportion and faster rate than their respective white counterparts. African Americans frequently present with a larger size tumor, do not undergo surgical resection, or receive radiation therapy as frequently as compared with their white peers. Barriers to timely and appropriate care should be further investigated in this group of at-risk patients.
0 Communities
1 Members
0 Resources
26 MeSH Terms
Adjuvant radiation therapy increases disease-free survival in stage IB Merkel cell carcinoma.
Sexton KW, Poteet SP, Hill JB, Schmidt A, Patel A, Del Corral GA, Axt J, Kelley MC, Thayer WP, Shack RB
(2014) Ann Plast Surg 73: 531-4
MeSH Terms: Adult, Aged, Aged, 80 and over, Carcinoma, Merkel Cell, Disease-Free Survival, Extremities, Female, Follow-Up Studies, Head and Neck Neoplasms, Humans, Kaplan-Meier Estimate, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Proportional Hazards Models, Radiotherapy, Adjuvant, Retrospective Studies, Skin Neoplasms, Torso, Treatment Outcome
Show Abstract · Added March 7, 2014
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. Adjuvant radiation increases survival in advanced stages, but efficacy in stage I disease is unknown. A retrospective review included all patients treated for stage I MCC during a 15-year period at Vanderbilt University Medical Center. Among 42 patients, 26 (62%) had a negative sentinel lymph node biopsy (stage IA) and 16 (38%) had clinically negative lymph nodes (stage IB) at the time of resection. Analysis using Cox regression revealed that higher stage and absence of adjuvant radiation are associated with increased disease recurrence (hazard ratio, 6.29; P=0.003 and hazard ratio, 4.69; P=0.013, respectively). Controlling for stage, radiation therapy significantly increased disease-free survival among patients with stage IB disease (P=0.0026) in a log-rank test comparing Kaplan-Meier curves. These findings support adjuvant radiation therapy in stage IB MCC patients with clinically negative lymph nodes who do not undergo sentinel lymph node biopsy.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Sonic hedgehog signaling directly targets Hyaluronic Acid Synthase 2, an essential regulator of phalangeal joint patterning.
Liu J, Li Q, Kuehn MR, Litingtung Y, Vokes SA, Chiang C
(2013) Dev Biol 375: 160-71
MeSH Terms: Aggrecans, Animals, Base Sequence, Body Patterning, Chondrogenesis, Extracellular Matrix Proteins, Extremities, Gene Expression Regulation, Developmental, Glucuronosyltransferase, Hedgehog Proteins, Hyaluronan Synthases, Hyaluronic Acid, Joints, Kruppel-Like Transcription Factors, Limb Buds, Mesoderm, Mice, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Promoter Regions, Genetic, Proteoglycans, Signal Transduction, Zinc Finger Protein Gli3
Show Abstract · Added October 25, 2013
Sonic hedgehog (Shh) signal, mediated by the Gli family of transcription factors, plays an essential role in the growth and patterning of the limb. Through analysis of the early limb bud transcriptome, we identified a posteriorly-enriched gene, Hyaluronic Acid Synthase 2 (Has2), which encodes a key enzyme for the synthesis of hyaluronan (HA), as a direct target of Gli transcriptional regulation during early mouse limb development. Has2 expression in the limb bud is lost in Shh null and expanded anteriorly in Gli3 mutants. We identified an ∼3kb Has2 promoter fragment that contains two strong Gli-binding consensus sequences, and mutation of either site abrogated the ability of Gli1 to activate Has2 promoter in a cell-based assay. Additionally, this promoter fragment is sufficient to direct expression of a reporter gene in the posterior limb mesenchyme. Chromatin immunoprecipitation of DNA-Gli3 protein complexes from limb buds indicated that Gli3 strongly binds to the Has2 promoter region, suggesting that Has2 is a direct transcriptional target of the Shh signaling pathway. We also showed that Has2 conditional mutant (Has2cko) hindlimbs display digit-specific patterning defects with longitudinally shifted phalangeal joints and impaired chondrogenesis. Has2cko limbs show less capacity for mesenchymal condensation with mislocalized distributions of chondroitin sulfate proteoglycans (CSPGs), aggrecan and link protein. Has2cko limb phenotype displays striking resemblance to mutants with defective chondroitin sulfation suggesting tight developmental control of HA on CSPG function. Together, our study identifies Has2 as a novel downstream target of Shh signaling required for joint patterning and chondrogenesis.
Copyright © 2013 Elsevier Inc. All rights reserved.
1 Communities
1 Members
0 Resources
24 MeSH Terms
Predictors and clinical significance of local recurrence in extremity soft tissue sarcoma.
Alamanda VK, Crosby SN, Archer KR, Song Y, Schwartz HS, Holt GE
(2013) Acta Oncol 52: 793-802
MeSH Terms: Adult, Aged, Cause of Death, Cohort Studies, Extremities, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Prognosis, Retrospective Studies, Risk Factors, Sarcoma, Survival Analysis, Treatment Outcome
Show Abstract · Added March 7, 2014
BACKGROUND - Limb salvage surgery (LSS) has gained widespread acceptance as the current treatment for treating extremity soft tissue sarcoma (STS) and has been greatly refined since its inception. Combined with improved adjuvant treatment modalities, rates of local relapse have greatly decreased. Nonetheless, local recurrence still occurs and identifying the cause and the subsequent effects of local recurrence can provide valuable insights as LSS continues to evolve.
METHODS - This retrospective study evaluated 278 patients treated for STS of the extremities between 2000 and 2006. Of these, 41 patients developed a local recurrence while 247 did not. Tumor characteristics and prognostic outcomes were analyzed. Wilcoxon rank sum test and either χ(2) or Fisher's exact was used to compare variables. Kaplan Meier and Gray's test for cumulative risk were also performed.
RESULTS - Patients who had a positive margin were 3.76 times more likely to develop local recurrence when compared to those with negative margins. This corresponds to a 38% risk of local recurrence if the margins were positive after six years vs. 12% if the margins were negative. In patients who underwent a re-excision, the presence or absence of residual disease upon re-excision did not have any bearing on local recurrence (p = 0.27). In comparing patients with and without local recurrence, there was no statistically significant difference in the rate and the proportion encountering distant metastasis and death due to sarcoma (p > 0.05).
CONCLUSIONS - Despite advancements in surgery, radiation and imaging, positive margins still occur, and the presence of positive margins following definitive treatment continues to remain as a strong predictor for local recurrence. While local recurrence represents a negative outcome for a patient, its impact on future prognosis is influenced by a variety of factors such as time to local recurrence as well as the tumor's inherent biological characteristics.
0 Communities
2 Members
0 Resources
17 MeSH Terms
Disparate Igf1 expression and growth in the fore- and hind limbs of a marsupial mammal (Monodelphis domestica).
Sears KE, Patel A, Hübler M, Cao X, Vandeberg JL, Zhong S
(2012) J Exp Zool B Mol Dev Evol 318: 279-93
MeSH Terms: Animals, DNA Primers, Extremities, Gene Expression Regulation, Developmental, Immunohistochemistry, In Situ Hybridization, Insulin-Like Growth Factor I, Microarray Analysis, Monodelphis, Reverse Transcriptase Polymerase Chain Reaction
Show Abstract · Added April 15, 2013
Proper regulation of growth is essential to all stages of life, from development of the egg into an embryo to the maintenance of normal cell cycle progression in adults. However, despite growth's importance to basic biology and health, little is known about how mammalian growth is regulated. In this study, we investigated the molecular basis of the highly disparate growth of opossum fore- and hind limbs in utero. We first used a novel, opossum-specific microarray to identify several growth-related genes that are differentially expressed in opossum fore- and hind limbs of comparable developmental stages. These genes included Igf1. Given Igf1's role in the growth of other systems, we further investigated the role of Igf1 in opossum limb growth. Supporting the microarray results, RT-PCR indicated that Igf1 levels are approximately two times higher in opossum fore- than hind limbs. Consistent with this, while Igf1 transcripts were readily detectable in opossum forelimbs using whole-mount in situ hybridization, they were not detectable in opossum hind limbs. Furthermore, opossum limbs treated with exogenous Igf1 protein experienced significantly greater cellular proliferation and growth than control limbs in vitro. Taken together, results suggest that the differential expression of Igf1 in developing opossum limbs contributes to their divergent rate of growth, and the unique limb phenotype of opossum newborns. This study establishes the opossum limb as a new mammalian model system for study of organ growth.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Primary excision compared with re-excision of extremity soft tissue sarcomas--is anything new?
Alamanda VK, Crosby SN, Archer KR, Song Y, Schwartz HS, Holt GE
(2012) J Surg Oncol 105: 662-7
MeSH Terms: Adult, Aged, Extremities, Female, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Metastasis, Neoplasm Recurrence, Local, Retrospective Studies, Sarcoma
Show Abstract · Added March 10, 2014
BACKGROUND - Soft tissue sarcomas (STS) are rare and are commonly excised outside of a sarcoma center without appropriate preoperative planning. Studies have shown varying results in survival and outcome when comparing patients undergoing re-excision to patients undergoing a single, planned excision.
METHODS - This retrospective study evaluated 278 patients treated for STS of the extremities between January 2000 and July 2006. One hundred seventy-two patients had a primary excision while 106 patients had a sarcoma re-excised. Survival curves for disease-free survival, metastasis-free survival, and local recurrence-free survival were calculated using competing risk analysis for both groups.
RESULTS - After adjusting for high-risk variables, our results indicate that re-excision is a proxy for smaller, low-grade tumors which tend to have a better survival profile. Death due to sarcoma and distant metastases were correlated with high-grade and large tumors. The presence of positive microscopic margins was the strongest predictor of local recurrence (P < 0.05).
CONCLUSIONS - There were no differences in death, metastases, or local recurrence between the two groups after adjusting for high-risk variables. Survival advantages previously reported with STS re-excision serve as proxy for tumors that have a better survival profile.
Copyright © 2011 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
12 MeSH Terms