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Combined CB2 receptor agonist and photodynamic therapy synergistically inhibit tumor growth in triple negative breast cancer.
Zhang J, Zhang S, Liu Y, Su M, Ling X, Liu F, Ge Y, Bai M
(2018) Photodiagnosis Photodyn Ther 24: 185-191
MeSH Terms: Acetamides, Animals, Apoptosis, Cell Line, Tumor, Cell Proliferation, Cell Survival, Combined Modality Therapy, Female, Gene Expression Regulation, Neoplastic, Humans, Indoles, Mice, Neoplasm Recurrence, Local, Phenyl Ethers, Photochemotherapy, Photosensitizing Agents, Quality of Life, Receptor, Cannabinoid, CB2, Receptors, GABA, Singlet Oxygen, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays
Show Abstract · Added April 2, 2019
Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because it is more aggressive, diagnosed at later stage and more likely to develop local and systemic recurrence. Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life. Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC. This combinatory therapy targets two proteins upregulated in TNBC: the cannabinoid CB2 receptor (CBR, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the combined CBR agonist and TSPO-PDT treatment resulted in synergistic inhibition in TNBC cell and tumor growth. This combinatory therapy approach provides new opportunities to treat TNBC with high efficacy. In addition, this study provides new evidence on the therapeutic potential of CBR agonists for cancer.
Copyright © 2018 Elsevier B.V. All rights reserved.
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22 MeSH Terms
Nodal Disease in Rectal Cancer Patients With Complete Tumor Response After Neoadjuvant Chemoradiation: Danger Below Calm Waters.
Baucom RB, Maguire LH, Kavalukas SL, Geiger TM, Ford MM, Muldoon RL, Hopkins MB, Hawkins AT
(2017) Dis Colon Rectum 60: 1260-1266
MeSH Terms: Adenocarcinoma, Case-Control Studies, Chemoradiotherapy, Combined Modality Therapy, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Neoplasm Staging, Neoplasm, Residual, Rectal Neoplasms, Retrospective Studies, Risk Factors, Survival Rate, Treatment Outcome, United States
Show Abstract · Added December 14, 2017
BACKGROUND - A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting."
OBJECTIVE - This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma.
DESIGN - This is a retrospective case control study.
SETTINGS - The National Cancer Database 2006 to 2014 was used to identify patients for this study.
PATIENTS - Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative.
MAIN OUTCOME MEASURES - The main outcome was nodal disease. The secondary outcome was overall survival.
RESULTS - A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002).
LIMITATIONS - This study was limited by the lack of clinical detail in the database and the inability to assess recurrence.
CONCLUSIONS - Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for "watchful waiting" strategies. See Video Abstract at http://links.lww.com/DCR/A458.
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19 MeSH Terms
Novel Airway and Ventilator Management of Tracheobronchial Disruption After Blunt Trauma.
Mehdiratta N, Archer M, Stewart M, Dennis B, Grogan E
(2017) Ann Thorac Surg 104: e359-e361
MeSH Terms: Accidents, Traffic, Bronchi, Bronchoscopy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Injury Severity Score, Middle Aged, Multiple Trauma, Positive-Pressure Respiration, Radiography, Thoracic, Risk Assessment, Thoracic Injuries, Trachea, Trauma Centers, Treatment Outcome, Wounds, Nonpenetrating
Show Abstract · Added February 3, 2018
Tracheobronchial injuries can be difficult to diagnose and manage, especially in the presence of polytrauma. A 50-year-old woman presented as a Level I trauma activation after being struck by a motor vehicle. Initial evaluation demonstrated intracranial hemorrhage and multiple chest injuries, including multilevel bilateral rib fractures, pneumomediastinum, and concern for tracheobronchial injury. After initial stabilization, bronchoscopy was performed and demonstrated an injury to the carina. We report a novel airway and ventilation strategy in the setting of concomitant tracheobronchial injury after severe blunt chest trauma in which extracorporeal support is contraindicated.
Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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18 MeSH Terms
Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.
Tamboli RA, Antoun J, Sidani RM, Clements A, Harmata EE, Marks-Shulman P, Gaylinn BD, Williams B, Clements RH, Albaugh VL, Abumrad NN
(2017) Diabetes Obes Metab 19: 1267-1275
MeSH Terms: Acylation, Anti-Obesity Agents, Cohort Studies, Combined Modality Therapy, Cross-Over Studies, Energy Metabolism, Gastric Bypass, Ghrelin, Gluconeogenesis, Glucose Clamp Technique, Human Growth Hormone, Humans, Infusions, Intravenous, Insulin Resistance, Liver, Muscle, Skeletal, Obesity, Morbid, Pancreatic Polypeptide, Pancreatic Polypeptide-Secreting Cells, Pituitary Gland, Anterior, Postoperative Care, Preoperative Care, Protein Precursors, Single-Blind Method
Show Abstract · Added April 3, 2017
AIMS - Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB).
MATERIALS AND METHODS - We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg  min ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp.
RESULTS - Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion.
CONCLUSIONS - These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
© 2017 John Wiley & Sons Ltd.
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24 MeSH Terms
Micrometastatic Dormancy in Uveal Melanoma: A Comprehensive Review of the Evidence, Mechanisms, and Implications for Future Adjuvant Therapies.
Nichols EE, Richmond A, Daniels AB
(2017) Int Ophthalmol Clin 57: 1-10
MeSH Terms: Chemotherapy, Adjuvant, Combined Modality Therapy, Humans, Melanoma, Molecular Targeted Therapy, Neoplasm Metastasis, Neoplasm Micrometastasis, Uveal Neoplasms
Added April 18, 2017
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8 MeSH Terms
HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.
Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Benson AB, Carrato A, Gulley ML, Jain D, Kakar S, Mackay HJ, Streutker C, Tang L, Troxell M, Ajani JA
(2016) Arch Pathol Lab Med 140: 1345-1363
MeSH Terms: Adenocarcinoma, Biomarkers, Tumor, Clinical Decision-Making, Combined Modality Therapy, Decision Trees, Diagnosis, Differential, Esophageal Neoplasms, Evidence-Based Medicine, Humans, Medical Oncology, Molecular Diagnostic Techniques, Molecular Targeted Therapy, Mutation, Neoplasm Grading, Neoplasm Staging, Pathology, Clinical, Receptor, ErbB-2, Societies, Medical, Stomach Neoplasms, United States
Show Abstract · Added March 14, 2018
CONTEXT - - ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.
OBJECTIVES - - To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.
DESIGN - - The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.
RESULTS - - The panel is proposing 11 recommendations with strong agreement from the open-comment participants.
RECOMMENDATIONS - - The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.
CONCLUSIONS - - This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.
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20 MeSH Terms
A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis.
Chao M, Wu H, Jin K, Li B, Wu J, Zhang G, Yang G, Hu X
(2016) Elife 5:
MeSH Terms: Acidosis, Lactic, Adult, Aged, Aged, 80 and over, Bicarbonates, Carcinoma, Chemoembolization, Therapeutic, Combined Modality Therapy, Female, Humans, Liver Neoplasms, Male, Middle Aged, Survival Analysis, Treatment Outcome
Show Abstract · Added May 4, 2017
STUDY DESIGN - Previous works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized (57 patients with large HCC) and a randomized controlled (20 patients with large HCC) studies.
METHODS - The patients were treated with transarterial chemoembolization (TACE) with or without bicarbonate local infusion into tumor.
RESULTS - In the nonrandomized controlled study, geometric mean of viable tumor residues (VTR) in TACE with bicarbonate was 6.4-fold lower than that in TACE without bicarbonate (7.1% [95% CI: 4.6%-10.9%] vs 45.6% [28.9%-72.0%]; p<0.0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate (ORR), whereas the ORR treated with TACE alone was 44.4% (nonrandomized) and 63.6% (randomized). The survival data suggested that bicarbonate may bring survival benefit.
CONCLUSION - Bicarbonate markedly enhances the anticancer activity of TACE.Clinical trail registration: ChiCTR-IOR-14005319.
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15 MeSH Terms
EGFR Fusions as Novel Therapeutic Targets in Lung Cancer.
Konduri K, Gallant JN, Chae YK, Giles FJ, Gitlitz BJ, Gowen K, Ichihara E, Owonikoko TK, Peddareddigari V, Ramalingam SS, Reddy SK, Eaby-Sandy B, Vavalà T, Whiteley A, Chen H, Yan Y, Sheehan JH, Meiler J, Morosini D, Ross JS, Stephens PJ, Miller VA, Ali SM, Lovly CM
(2016) Cancer Discov 6: 601-11
MeSH Terms: Adult, Antineoplastic Agents, Biomarkers, Cell Line, Tumor, Combined Modality Therapy, ErbB Receptors, Exons, Female, Genetic Loci, High-Throughput Nucleotide Sequencing, Humans, Introns, Lung Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Models, Molecular, Molecular Targeted Therapy, Neoplasm Metastasis, Oncogene Proteins, Fusion, Protein Conformation, Protein Kinase Inhibitors, Rad51 Recombinase, Young Adult
Show Abstract · Added April 8, 2017
UNLABELLED - Here, we report that novel epidermal growth factor receptor (EGFR) gene fusions comprising the N-terminal of EGFR linked to various fusion partners, most commonly RAD51, are recurrent in lung cancer. We describe five patients with metastatic lung cancer whose tumors harbored EGFR fusions, four of whom were treated with EGFR tyrosine kinase inhibitors (TKI) with documented antitumor responses. In vitro, EGFR-RAD51 fusions are oncogenic and can be therapeutically targeted with available EGFR TKIs and therapeutic antibodies. These results support the dependence of EGFR-rearranged tumors on EGFR-mediated signaling and suggest several therapeutic strategies for patients whose tumors harbor this novel alteration.
SIGNIFICANCE - We report for the first time the identification and therapeutic targeting of EGFR C-terminal fusions in patients with lung cancer and document responses to the EGFR inhibitor erlotinib in 4 patients whose tumors harbored EGFR fusions. Findings from these studies will be immediately translatable to the clinic, as there are already several approved EGFR inhibitors. Cancer Discov; 6(6); 601-11. ©2016 AACR.See related commentary by Paik, p. 574This article is highlighted in the In This Issue feature, p. 561.
©2016 American Association for Cancer Research.
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24 MeSH Terms
The Intensive Diet and Exercise for Arthritis (IDEA) trial: 18-month radiographic and MRI outcomes.
Hunter DJ, Beavers DP, Eckstein F, Guermazi A, Loeser RF, Nicklas BJ, Mihalko SL, Miller GD, Lyles M, DeVita P, Legault C, Carr JJ, Williamson JD, Messier SP
(2015) Osteoarthritis Cartilage 23: 1090-8
MeSH Terms: Aged, Body Mass Index, Combined Modality Therapy, Diet, Reducing, Disease Progression, Exercise Therapy, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Osteoarthritis, Knee, Radiography, Severity of Illness Index, Single-Blind Method, Treatment Outcome, Weight Loss
Show Abstract · Added August 24, 2015
PURPOSE - Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA).
METHODS - Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27-41 kg m(-2)) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender.
RESULTS - Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D -0.07 (SE 0.22) mm, D + E -0.27 (SE 0.22) mm and E -0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D -0.10(0.05) mm, D + E -0.13(0.04) mm and E -0.05(0.04) mm (P = 0.42).
CONCLUSION - Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.
Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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19 MeSH Terms
A Multimodal Intervention Improves Postanesthesia Care Unit Handovers.
Weinger MB, Slagle JM, Kuntz AH, Schildcrout JS, Banerjee A, Mercaldo ND, Bills JL, Wallston KA, Speroff T, Patterson ES, France DJ
(2015) Anesth Analg 121: 957-71
MeSH Terms: Adult, Aged, Anesthesia, Cohort Studies, Combined Modality Therapy, Continuity of Patient Care, Female, Follow-Up Studies, Humans, Male, Middle Aged, Patient Handoff, Postoperative Care
Show Abstract · Added July 28, 2015
BACKGROUND - Failures of communication are a major contributor to perioperative adverse events. Transitions of care may be particularly vulnerable. We sought to improve postoperative handovers.
METHODS - We introduced a multimodal intervention in an adult and a pediatric postanesthesia care unit (PACU) to improve postoperative handovers between anesthesia providers (APs) and PACU registered nurses (RNs). The intervention included a standardized electronic handover report form, a didactic webinar, mandatory simulation training focused on improving interprofessional communication, and post-training performance feedback. Trained, blinded nurse observers scored PACU handovers during 17 months using a structured tool consisting of 8 subscales and a global score (1-5 scale). Multivariate logistic regression assessed the effect of the intervention on the proportion of observed handovers receiving a global effectiveness rating of ≥3.
RESULTS - Four hundred fifty-two clinicians received the simulation-based training, and 981 handovers were observed and rated. In the adult PACU, the estimated percentages of acceptable handovers (global ratings ≥3) among AP-RN pairs, where neither received simulation-based training (untrained dyads), was 3% (95% confidence interval, 1%-11%) at day 0, 10% (5%-19%) at training initiation (day 40), and 57% (33%-78%) at 1-year post-training initiation (day 405). For AP-RN pairs where at least one received the simulation-based training (trained dyads), these percentages were estimated to be 18% (11%-28%) and 68% (57%-76%) on days 40 and 405, respectively. The percentage of acceptable handovers was significantly greater on day 405 than it was on day 40 for both untrained (P < 0.001) and trained dyads (P < 0.001). Similar patterns were observed in the pediatric PACU. Three years later, the unadjusted estimate of the probability of an acceptable handover was 87% (72%-95%) in the adult PACU and 56% (40%-72%) in the pediatric PACU.
CONCLUSIONS - A multimodal intervention substantially improved interprofessional PACU handovers, including those by clinicians who had not undergone formal simulation training. An effect appeared to be present >3 years later.
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13 MeSH Terms