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Cumulative incidence of neck recurrence with increasing depth of invasion.
Shinn JR, Wood CB, Colazo JM, Harrell FE, Rohde SL, Mannion K
(2018) Oral Oncol 87: 36-42
MeSH Terms: Aged, Female, Follow-Up Studies, Glossectomy, Humans, Incidence, Lymph Nodes, Lymphatic Metastasis, Male, Middle Aged, Neck, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasm Staging, Retrospective Studies, Tongue, Tongue Neoplasms, Treatment Outcome
Show Abstract · Added November 7, 2019
OBJECTIVE - To determine if there is a critical depth of invasion that predicts micrometastasis in early oral tongue cancer.
METHODS - Retrospective series identifying patients undergoing primary surgical resection of T1 or T2 oral tongue cancer who elected against neck treatment between 2000 and 2015. Cox proportional-hazard model compared the relative hazard and cumulative incidence of recurrence to depth of invasion. The model used a 2 parameter quadratic effect for depth that was chosen based on Akaike's information criterion.
RESULTS - Ninety-three patients were identified with T1 or T2 oral tongue squamous cell carcinoma and clinically N0 neck undergoing glossectomy without elective neck treatment. 61% were male and median age was 60 years. Median follow up was 45 months, and 76 patients had at least two years of follow up. Thirty-six of 76 patients recurred (47.4%), with 15 recurring in the oral cavity (19.7%) and 21 developing nodal metastasis (27.6%). Cox proportional-hazards quadratic polynomial showed increasing hazard of recurrence with depth of invasion and the cumulative incidence increased sharply within the range of data from 2 to 6 mm depth of invasion.
CONCLUSIONS - Depth of invasion is significantly associated with nodal metastasis and has been added to the 8th AJCC staging guidelines. Variable depths of invasion have been associated with regional metastasis; however, there is likely not a critical depth that predicts neck recurrence due to progressive hazards and cumulative risk of occult metastasis. The risk of regional metastasis is likely much greater than previously believed and increases progressively with increasing depth.
Copyright © 2018 Elsevier Ltd. All rights reserved.
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18 MeSH Terms
Circulating Tumor Cells: Diagnostic and Therapeutic Applications.
Lin E, Cao T, Nagrath S, King MR
(2018) Annu Rev Biomed Eng 20: 329-352
MeSH Terms: Animals, Cell Separation, Electrophoresis, Epithelial Cells, Filtration, Humans, Lab-On-A-Chip Devices, Lymph Nodes, Lymphatic Metastasis, Lymphatic System, Neoplasm Metastasis, Neoplasms, Neoplastic Cells, Circulating, Prognosis, TNF-Related Apoptosis-Inducing Ligand
Show Abstract · Added April 15, 2019
Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.
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15 MeSH Terms
Intracellular Staining and Flow Cytometry to Identify Lymphocyte Subsets within Murine Aorta, Kidney and Lymph Nodes in a Model of Hypertension.
Laroumanie F, Dale BL, Saleh MA, Madhur MS
(2017) J Vis Exp :
MeSH Terms: Angiotensin II, Animals, Aorta, Cytokines, Disease Models, Animal, Flow Cytometry, Hypertension, Kidney, Lymph Nodes, Mice, Staining and Labeling, T-Lymphocyte Subsets
Show Abstract · Added September 7, 2017
It is now well known that T lymphocytes play a critical role in the development of several cardiovascular diseases. For example, studies from our group have shown that hypertension is associated with an excessive accumulation of T cells in the vessels and kidney during the development of experimental hypertension. Once in these tissues, T cells produce several cytokines that affect both vascular and renal function leading to vasoconstriction and sodium and water retention. To fully understand how T cells cause cardiovascular and renal diseases, it is important to be able to identify and quantify the specific T cell subsets present in these tissues. T cell subsets are defined by a combination of surface markers, the cytokines they secrete, and the transcription factors they express. The complexity of the T cell population makes flow cytometry and intracellular staining an invaluable technique to dissect the phenotypes of the lymphocytes present in tissues. Here, we provide a detailed protocol to identify the surface and intracellular markers (cytokines and transcription factors) in T cells isolated from murine kidney, aorta and aortic draining lymph nodes in a model of angiotensin II induced hypertension. The following steps are described in detail: isolation of the tissues, generation of the single cell suspensions, ex vivo stimulation, fixation, permeabilization and staining. In addition, several fundamental principles of flow cytometric analyses including choosing the proper controls and appropriate gating strategies are discussed.
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12 MeSH Terms
Omission of Adjuvant Chemotherapy Is Associated With Increased Mortality in Patients With T3N0 Colon Cancer With Inadequate Lymph Node Harvest.
Wells KO, Hawkins AT, Krishnamurthy DM, Dharmarajan S, Glasgow SC, Hunt SR, Mutch MG, Wise P, Silviera ML
(2017) Dis Colon Rectum 60: 15-21
MeSH Terms: Adenocarcinoma, Aged, Aged, 80 and over, Chemotherapy, Adjuvant, Colectomy, Colon, Colonic Neoplasms, Databases, Factual, Female, Guideline Adherence, Humans, Lymph Node Excision, Lymph Nodes, Male, Middle Aged, Neoplasm Staging, Practice Guidelines as Topic, Retrospective Studies, Survival Rate
Show Abstract · Added March 21, 2017
BACKGROUND - Adjuvant chemotherapy for T3N0 colon cancer is controversial. National guidelines recommend its use in patients with stage II with high-risk features, including lymph node harvest of less than 12, yet this treatment is underused.
OBJECTIVE - The purpose of this study was to demonstrate that the use of adjuvant chemotherapy in patients with T3N0 adenocarcinoma with inadequate lymph node harvest is beneficial.
DESIGN - This was a retrospective population-based study of patients with resected T3N0 adenocarcinoma of the colon.
SETTINGS - The National Cancer Database was queried from 2003 to 2012.
PATIENTS - A total of 134,567 patients with T3N0 colon cancer were included in this analysis.
MAIN OUTCOME MEASURES - The use of chemotherapy, short-term outcomes, and overall survival was evaluated. Clinicopathologic factors associated with omission of chemotherapy were also analyzed.
RESULTS - Inadequate lymph node harvest was observed in 23.3% of patients, and this rate decreased over the study period from 46.8% in 2003 to 12.5% in 2012 (p < 0.0001). Overall 5-year survival for patients with T3N0 cancer was 66.8%. Inadequate lymph node harvest among these patients was associated with lower overall 5-year survival (58.7% vs 69.8%; p < 0.001). The use of adjuvant chemotherapy among patients with T3N0 cancer after inadequate lymph node harvest was only 16.7%. In a multivariable analysis, factors associated with failure to receive chemotherapy included advanced age (OR = 0.44 (95% CI, 0.43-0.45)), increased comorbidities (OR = 0.7 (95% CI, 0.66-0.76)), and postoperative readmission (OR = 0.78 (95% CI, 0.67-0.91)). Patients with inadequate lymph node harvest who received adjuvant chemotherapy had improved 5-year survival (chemotherapy, 78.4% vs no chemotherapy, 54.7%; p < 0.001). Even when controlling for all of the significant variables, the administration of chemotherapy remained a predictor of decreased mortality (HR = 0.57 (95% CI, 0.54-0.60); p < 0.001).
LIMITATIONS - This study was limited by its retrospective, population-based design.
CONCLUSIONS - Patients with T3N0 colon cancer with inadequate lymph node harvest who receive adjuvant chemotherapy have increased overall survival. Despite this survival benefit, a fraction of these patients receive adjuvant chemotherapy. Barriers to chemotherapy are multifactorial.
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19 MeSH Terms
Is Endobronchial Ultrasound Influenced by Sedation Strategy? Comparing Apples to Apples.
Sasieta H, Mandrekar J, Maldonado F
(2015) Am J Respir Crit Care Med 191: 1469-70
MeSH Terms: Anesthesia, General, Conscious Sedation, Female, Humans, Image-Guided Biopsy, Lymph Nodes, Male, Neoplasms, Sentinel Lymph Node Biopsy
Added July 28, 2015
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9 MeSH Terms
Assessment of lymphatic impairment and interstitial protein accumulation in patients with breast cancer treatment-related lymphedema using CEST MRI.
Donahue MJ, Donahue PC, Rane S, Thompson CR, Strother MK, Scott AO, Smith SA
(2016) Magn Reson Med 75: 345-55
MeSH Terms: Adult, Aged, Biomarkers, Breast Neoplasms, Female, Humans, Lymph Nodes, Lymphedema, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Middle Aged, Molecular Imaging, Proteins, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome
Show Abstract · Added February 16, 2016
PURPOSE - Lymphatic impairment is known to reduce quality of life in some of the most crippling diseases of the 21st century, including obesity, lymphedema, and cancer. However, the lymphatics are not nearly as well-understood as other bodily systems, largely owing to a lack of sensitive imaging technologies that can be applied using standard clinical equipment. Here, proton exchange-weighted MRI is translated to the lymphatics in patients with breast cancer treatment-related lymphedema (BCRL).
METHODS - Healthy volunteers (N = 8) and BCRL patients (N = 7) were scanned at 3 Tesla using customized structural MRI and amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI in sequence with the hypothesis that APT effects would be elevated in lymphedematous tissue. APT contrast, lymphedema stage, symptomatology, and histology information were evaluated.
RESULTS - No significant difference between proton-weighted APT contrast in the right and left arms of healthy controls was observed. An increase in APT contrast in the affected arms of patients was found (P = 0.025; Cohen's d = 2.4), and variability among patients was consistent with documented damage to lymphatics as quantified by lymphedema stage.
CONCLUSION - APT CEST MRI may have relevance for evaluating lymphatic impairment in patients with BCRL, and may extend to other pathologies where lymphatic compromise is evident.
© 2015 Wiley Periodicals, Inc.
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16 MeSH Terms
Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells.
Wen Y, Liu W, Bagia C, Zhang S, Bai M, Janjic JM, Giannoukakis N, Gawalt ES, Meng WS
(2014) Acta Biomater 10: 4759-4767
MeSH Terms: Amino Acid Sequence, Animals, Antibodies, Antigen-Presenting Cells, Cell Membrane, Computer Systems, Emulsions, Female, Graft Rejection, Immobilized Proteins, Immunoglobulin G, Interferon-gamma, Lymph Nodes, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Nanoparticles, Neutralization Tests, Peptides, Skin, Skin Transplantation, Spectroscopy, Near-Infrared, T-Lymphocytes, Transplantation, Homologous
Show Abstract · Added April 2, 2019
We report herein application of an in situ material strategy to attenuate allograft T cell responses in a skin transplant mouse model. Functionalized peptidic membranes were used to impede trafficking of donor antigen-presenting cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self-assembling peptides (SAPs) presenting antibodies were found to remain underneath grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted by using a monoclonal antibody that binds to a class II major histocompatibility complex (MHC) molecule (I-A(d)) expressed exclusively by donor cells. Using a novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in allografts treated with membranes loaded with anti-I-A(d) antibodies than without. In vitro, dAPCs released from skin explants were found adsorbed preferentially on anti-I-A(d) antibody-loaded membranes. Recipient T cells from these mice produced lower concentrations of interferon-gamma cultured ex vivo with donor cells. Taken together, the data indicate that the strategy has the potential to alter the natural course of rejection immune mechanisms in allogeneic transplant models.
Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g.
Gérard A, Patino-Lopez G, Beemiller P, Nambiar R, Ben-Aissa K, Liu Y, Totah FJ, Tyska MJ, Shaw S, Krummel MF
(2014) Cell 158: 492-505
MeSH Terms: Animals, Antigen-Presenting Cells, Cell Membrane, Cell Movement, Immunologic Surveillance, Lymph Nodes, Mice, Minor Histocompatibility Antigens, Myosins, Receptors, Antigen, T-Cell, T-Lymphocytes
Show Abstract · Added January 21, 2015
To mount an immune response, T lymphocytes must successfully search for foreign material bound to the surface of antigen-presenting cells. How T cells optimize their chances of encountering and responding to these antigens is unknown. T cell motility in tissues resembles a random or Levy walk and is regulated in part by external factors including chemokines and lymph-node topology, but motility parameters such as speed and propensity to turn may also be cell intrinsic. Here we found that the unconventional myosin 1g (Myo1g) motor generates membrane tension, enforces cell-intrinsic meandering search, and enhances T-DC interactions during lymph-node surveillance. Increased turning and meandering motility, as opposed to ballistic motility, is enhanced by Myo1g. Myo1g acts as a "turning motor" and generates a form of cellular "flânerie." Modeling and antigen challenges show that these intrinsically programmed elements of motility search are critical for the detection of rare cognate antigen-presenting cells.
Copyright © 2014 Elsevier Inc. All rights reserved.
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11 MeSH Terms
Focal tracheal stenosis due to intramural hematoma following endobronchial ultrasound-guided transbronchial needle aspiration.
Al-Qadi MO, Maldonado F
(2014) J Bronchology Interv Pulmonol 21: 274-6
MeSH Terms: Aged, Bronchoscopy, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Female, Hematoma, Humans, Lymph Nodes, Mediastinum, Tracheal Diseases, Tracheal Stenosis
Show Abstract · Added July 28, 2015
Tracheal obstruction can present insidiously or be acute and life threatening. This condition can occur acutely, as in cases of infection or foreign body aspiration, whereas posttraumatic tracheal stenosis or obstruction due to intraluminal tumor growth typically evolves more gradually. Tracheal stenosis secondary to intramural hematoma is exceedingly rare. We report a case of intramural tracheal hematoma causing obstruction following endobronchial ultrasound-guided transbronchial needle aspiration in a 69-year-old woman.
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10 MeSH Terms
CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2 and activation of MEK and PI3K pathways.
Sobolik T, Su YJ, Wells S, Ayers GD, Cook RS, Richmond A
(2014) Mol Biol Cell 25: 566-82
MeSH Terms: Animals, Breast Neoplasms, Cell Line, Tumor, Cell Movement, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Genetic Association Studies, HEK293 Cells, HL-60 Cells, Humans, Lymph Nodes, MAP Kinase Signaling System, MCF-7 Cells, Mice, Mice, Inbred BALB C, Mice, Nude, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Phosphatidylinositol Phosphates, Receptors, CXCR4, Receptors, Interleukin-8B, Signal Transduction, Up-Regulation
Show Abstract · Added March 14, 2014
Aberrant expression of CXCR4 in human breast cancer correlates with metastasis to tissues secreting CXCL12. To understand the mechanism by which CXCR4 mediates breast cancer metastasis, MCF-7 breast carcinoma cells were transduced to express wild-type CXCR4 (CXCR4WT) or constitutively active CXCR4 (CXCR4ΔCTD) and analyzed in two-dimensional (2D) cultures, three-dimensional reconstituted basement membrane (3D rBM) cultures, and mice using intravital imaging. Two-dimensional cultures of MCF-7 CXCR4ΔCTD cells, but not CXCR4WT, exhibited an epithelial-to-mesenchymal transition (EMT) characterized by up-regulation of zinc finger E box-binding homeobox 1, loss of E-cadherin, up-regulation of cadherin 11, p120 isoform switching, activation of extracellular signal-regulated kinase 1/2, and matrix metalloproteinase-2. In contrast to the 2D environment, MCF-7 CXCR4WT cells cultured in 3D rBM exhibited an EMT phenotype, accompanied by expression of CXCR2, CXCR7, CXCL1, CXCL8, CCL2, interleukin-6, and granulocyte-macrophage colony stimulating factor. Dual inhibition of CXCR2 with CXCR4, or inhibition of either receptor with inhibitors of mitogen-activated protein kinase 1 or phosphatidylinositol 3-kinase, reversed the aggressive phenotype of MCF-7 CXCR4-expressing or MDA-MB-231 cells in 3D rBM. Intravital imaging of CXCR4-expressing MCF-7 cells revealed that tumor cells migrate toward blood vessels and metastasize to lymph nodes. Thus CXCR4 can drive EMT along with an up-regulation of chemokine receptors and cytokines important in cell migration, lymphatic invasion, and tumor metastasis.
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25 MeSH Terms