Scholars@Duke
Takuya Osada

Takuya Osada

Adjunct Associate Professor in the Department of Surgery
Surgery, Surgical Sciences
osada001@mc.duke.edu
Box 2606 Med Ctr, Durham, NC 27710
401 Med Sci Res Bldg, Durham, NC 27710

Scholarly Works - Journal articles

Clinical trials of self-replicating RNA-based cancer vaccines.

Journal article Cancer Gene Ther · June 2023 Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. T ... Full text Link to item Cite

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Journal article Int J Hyperthermia · 2023 Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, h ... Full text Link to item Cite

A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.

Journal article Cancers (Basel) · November 23, 2022 Ductal carcinoma in situ (DCIS) of the breast is often managed by lumpectomy and radiation or mastectomy, despite its indolent features. Effective non-invasive treatment strategies could reduce the morbidity of DCIS treatment. We have exploited the high he ... Full text Link to item Cite

Combination of a novel heat shock protein 90-targeted photodynamic therapy with PD-1/PD-L1 blockade induces potent systemic antitumor efficacy and abscopal effect against breast cancers.

Journal article J Immunother Cancer · September 2022 BACKGROUND: We previously demonstrated potent antitumor activity against human breast cancer xenografts using photodynamic therapy (PDT) targeting a novel tumor-specific photosensitizer (HS201), which binds heat shock protein 90 (HS201-PDT). However, induc ... Full text Link to item Cite

Sensitizing immune unresponsive colorectal cancers to immune checkpoint inhibitors through MAVS overexpression.

Journal article J Immunother Cancer · March 2022 BACKGROUND: The majority of colorectal carcinomas (CRCs) are insensitive to programmed death protein-1/programmed death-ligand 1 (anti-PD-1/PD-L1) immune checkpoint inhibitor (ICI) antibodies. While there are many causes for ICI insensitivity, recent studi ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity.

Journal article J Immunother Cancer · January 2022 BACKGROUND: Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic an ... Full text Link to item Cite

Intratumoral Plasmid IL12 Expands CD8+ T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.

Journal article Clin Cancer Res · May 1, 2021 PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority o ... Full text Link to item Cite

Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.

Journal article J Immunother Cancer · November 2020 BACKGROUND: There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vacc ... Full text Link to item Cite

Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.

Journal article Commun Biol · May 8, 2020 Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a ... Full text Link to item Cite

Impact of synchronized anti-PD-1 with Ad-CEA vaccination on inhibition of colon cancer growth.

Journal article Immunotherapy · August 2019 Aim: The purpose of this study was to determine whether addition of anti-PD-1 antibody increased the immunogenicity and anti-tumor activity of Ad-CEA vaccination in a murine model of colon cancer. Methods: Ad-CEA was administered prior to implantation of M ... Full text Link to item Cite

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study.

Journal article Clin Cancer Res · May 1, 2019 PURPOSE: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic dr ... Full text Open Access Link to item Cite

Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.

Journal article Biochem J · February 8, 2019 The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously, we identified that the anthelmintic drug niclosamide inhibited Wnt signaling by prom ... Full text Link to item Cite

Right Time and Place for IL12: Targeted Delivery Stimulates Immune Therapy.

Journal article Clin Cancer Res · January 1, 2019 Systemic IL12 therapy has potent antitumor effects, but clinical delivery of this potent cytokine has been complicated by systemic toxicity. A novel strategy to deliver IL12 to the tumor microenvironment appears promising in a first-in-human study, appeari ... Full text Link to item Cite

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers.

Journal article Breast Cancer Res · August 9, 2018 BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor recepto ... Full text Link to item Cite

In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

Journal article Clin Cancer Res · December 15, 2017 Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast ... Full text Link to item Cite

A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo.

Journal article ACS Chem Biol · April 21, 2017 Extracellular expression of heat shock protein 90 (eHsp90) by tumor cells is correlated with malignancy. Development of small molecule probes that can detect eHsp90 in vivo may therefore have utility in the early detection of malignancy. We synthesized a c ... Full text Link to item Cite

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

Journal article Oncoimmunology · 2017 Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicabil ... Full text Link to item Cite

Multi-site Measurements of Muscle O2 Dynamics During Cycling Exercise in Early Post-myocardial Infarction.

Journal article Adv Exp Med Biol · 2017 The aim of this study was to compare the muscle oxygen dynamics between early post-myocardial infarction (n = 12; MI) and age-matched elderly subjects without MI (n = 12; CON) in several leg muscles during ramp cycling exercise. Muscle oxygen saturation (S ... Full text Link to item Cite

Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET.

Journal article J Nucl Med · June 2016 UNLABELLED: The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. Immuno-PET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could b ... Full text Link to item Cite

WE-FG-BRA-01: Cancer Treatment Utilizing Photo-Activation of Psoralen with KV X-Rays.

Journal article Med Phys · June 2016 PURPOSE: This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with immunogenic anti-cancer potential. Psoralen therapies have been li ... Full text Link to item Cite

Aerobic training enhances muscle deoxygenation in early post-myocardial infarction.

Journal article Eur J Appl Physiol · April 2016 PURPOSE: Exercise-induced skeletal muscle deoxygenation is startling by its absence in early post-myocardial infarction (MI) patients. Exercise training early post-MI is associated with reduced cardiovascular risk and increased aerobic capacity. We therefo ... Full text Link to item Cite

X-Ray Psoralen Activated Cancer Therapy (X-PACT).

Journal article PLoS One · 2016 This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photo ... Full text Open Access Link to item Cite

Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth.

Journal article Breast Cancer Res · December 2015 Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kina ... Full text Link to item Cite

Mechanical compression during repeated sustained isometric muscle contractions and hyperemic recovery in healthy young males.

Journal article J Physiol Anthropol · October 31, 2015 BACKGROUND: An elevated intramuscular pressure during a single forearm isometric muscle contraction may restrict muscle hyperemia. However, during repeated isometric exercise, it is unclear to what extent mechanical compression and muscle vasodilatation co ... Full text Link to item Cite

CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1.

Journal article Cancer Immunol Immunother · June 2015 Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA ex ... Full text Link to item Cite

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

Journal article J Immunother · May 2015 Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optim ... Full text Link to item Cite

Once-weekly muscle endurance and strength training prevents deterioration of muscle oxidative function and attenuates the degree of strength decline during 3-week forearm immobilization.

Journal article Eur J Appl Physiol · March 2015 PURPOSE: Muscle unloading causes muscle function deterioration, but the extent to which training frequency or volume can be reduced while preserving muscle function during muscle unloading is unknown. We examined the effects of low-volume muscle endurance ... Full text Link to item Cite

Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth.

Journal article Breast Cancer Res · February 15, 2015 INTRODUCTION: Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 ... Full text Link to item Cite

Determining effect of food intake on comprehensive abdominal-pelvic visceral blood flow by Doppler ultrasound

Journal article Journal of Tokyo Medical University · January 1, 2015 Aim: Comprehensive arterial blood flow (BF) in the abdominal-pelvic viscera (BFVis) can be calculated by subtracting right and left femoral arterial BF (BFRFA and BFLFA, respectively) from upper abdominal aorta BF (BFAo) above the coeliac trunk. The aim of ... Cite

Skeletal muscle deoxygenation abnormalities in early post-myocardial infarction.

Journal article Med Sci Sports Exerc · November 2014 PURPOSE: Reduced peak aerobic capacity in chronic heart failure can be partly explained by impaired peripheral factors. However, skeletal muscle deoxygenation responses during exercise and their relation to peak aerobic capacity have not been fully establi ... Full text Link to item Cite

Designing effective vaccines for colorectal cancer.

Journal article Immunotherapy · 2014 Achieving long-term control of colorectal cancers with therapeutic vaccines that generate potent anti-tumor T cell and antibody responses has been a goal for more than two decades. To date, clinical trials of these vaccines have demonstrated induction of i ... Full text Link to item Cite

Modulation of immune system inhibitory checkpoints in colorectal cancer

Journal article Current Colorectal Cancer Reports · December 1, 2013 T cell infiltration of colorectal cancer is associated with improved clinical outcome, underlining the importance of the immune system in cancer control; however, immune checkpoints, including the inhibitory T cell molecules CTLA-4 and PD-1 that temper the ... Full text Cite

Optical and radioiodinated tethered Hsp90 inhibitors reveal selective internalization of ectopic Hsp90 in malignant breast tumor cells.

Journal article Chem Biol · September 19, 2013 Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained, but could be influenced by ectopically expressed Hsp90 in tumors. In this work ... Full text Link to item Cite

Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment.

Journal article J Clin Invest · September 2013 Cancers subvert the host immune system to facilitate disease progression. These evolved immunosuppressive mechanisms are also implicated in circumventing immunotherapeutic strategies. Emerging data indicate that local tumor-associated DC populations exhibi ... Full text Open Access Link to item Cite

Biomarkers and correlative endpoints for immunotherapy trials.

Journal article Am Soc Clin Oncol Educ Book · 2013 Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer ... Full text Link to item Cite

Modulation of Immune System Inhibitory Checkpoints in Colorectal Cancer

Journal article Current Colorectal Cancer Reports · 2013 Cite

An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models.

Journal article Breast Cancer Res · 2013 INTRODUCTION: The human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase (RTK) oncogene is an attractive therapeutic target for the treatment of HER2-addicted tumors. Although lapatinib, an FDA-approved small-molecule HER2 and epidermal g ... Full text Link to item Cite

Abstract P4-08-07: Novel insight into the tumor “flare” phenomenon and lapatinib resistance

Journal article Cancer Research · December 15, 2012 AbstractBACKGROUND: Resistance to lapatinib generally develops in approximately half of patients within one year of initiating treatment. When lapatinib is withdrawn, there is often a rapid progression of di ... Full text Cite

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

Journal article Cancer Immunol Immunother · November 2012 We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing i ... Full text Link to item Cite

Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.

Journal article Mol Cancer Ther · July 2012 Despite advances in contemporary chemotherapeutic strategies, long-term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is need ... Full text Link to item Cite

Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells.

Journal article Breast Cancer Res · June 7, 2012 INTRODUCTION: Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing ... Full text Link to item Cite

Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy.

Journal article Semin Oncol · June 2012 Although cellular immunotherapy based on autolgous dendritic cells (DCs) targeting antigens expressed by metastatic cancer has demonstrated clinical efficacy, the logistical challenges in generating an individualized cell product create an imperative to de ... Full text Link to item Cite

Immunodominant liver-specific expression suppresses transgene-directed immune responses in murine pompe disease.

Journal article Hum Gene Ther · May 2012 Pompe disease can be treated effectively, if immune tolerance to enzyme replacement therapy (ERT) with acid α-glucosidase (GAA) is present. An adeno-associated viral (AAV) vector carrying a liver-specific regulatory cassette to drive GAA expression (AAV-LS ... Full text Open Access Link to item Cite

Physiological aspects of the determination of comprehensive arterial inflows in the lower abdomen assessed by Doppler ultrasound.

Journal article Cardiovasc Ultrasound · March 26, 2012 Non-invasive measurement of splanchnic hemodynamics has been utilized in the clinical setting for diagnosis of gastro-intestinal disease, and for determining reserve blood flow (BF) distribution. However, previous studies that measured BF in a "single vess ... Full text Link to item Cite

Relationship between reduced lower abdominal blood flows and heart rate in recovery following cycling exercise.

Journal article Acta Physiol (Oxf) · March 2012 AIM: To examine the blood flow (BF) response in the lower abdomen (LAB) in recovery following upright cycling exercise at three levels of relative maximum pulmonary oxygen consumption (VO(2max)) and the relationship of BF(LAB) to heart rate (HR) and target ... Full text Link to item Cite

Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected].

Journal article J Transl Med · February 10, 2012 BACKGROUND: Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccin ... Full text Link to item Cite

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Journal article PLoS One · 2012 Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying ... Full text Link to item Cite

Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.

Journal article PLoS One · 2012 Breast cancers with a basal-like gene signature are primarily triple-negative, frequently metastatic, and carry a poor prognosis. Basal-like breast cancers are enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal tr ... Full text Link to item Cite

Increasing vaccine potency through exosome antigen targeting.

Journal article Vaccine · November 21, 2011 While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to e ... Full text Link to item Cite

Truncated ErbB2 expressed in tumor cell nuclei contributes to acquired therapeutic resistance to ErbB2 kinase inhibitors.

Journal article Mol Cancer Ther · August 2011 ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185(ErbB2)). In addition to p185(ErbB2), truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumo ... Full text Link to item Cite

Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

Journal article Clin Cancer Res · July 15, 2011 PURPOSE: The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); howe ... Full text Link to item Cite

HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis.

Journal article Cancer Res · July 1, 2011 HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored ... Full text Link to item Cite

Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

Journal article Cancer Res · June 15, 2011 Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevel ... Full text Link to item Cite

A dendritic cell-based vaccine effects on T-cell responses compared with a viral vector vaccine when administered to patients following resection of colorectal metastases in a randomized phase II study.

Journal article J Clin Oncol · May 20, 2011 2533 Background: CD8+ T cell responses to colorectal cancer are associated with longer survival. This has led to the hypothesis that cancer vaccines, capable of activating T cell responses, may improve clinical outcome. Vaccines based on antigen-presenting ... Link to item Cite

Survival rates among patients vaccinated following resection of colorectal cancer metastases in a phase II randomized study compared with contemporary controls.

Journal article J Clin Oncol · May 20, 2011 3557 Background: Patients with completely resected metastases from colorectal cancer (CRC) remain at high risk of recurrence and death despite adjuvant chemotherapy. Recently, survival of prostate cancer patients was enhanced by antigen-presenting cell the ... Link to item Cite

MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

Journal article Clin Cancer Res · May 15, 2011 PURPOSE: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-c ... Full text Link to item Cite

Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

Journal article Immunol Res · April 2011 Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these ther ... Full text Link to item Cite

Development of an assay to predict oxaliplatin sensitivity from formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues.

Journal article J Clin Oncol · February 2011 429 Background: Genomic profiling has improved our understanding of the underlying biology of tumors, accuracy of diagnosing disease, predictions of the courses of disease, and ability to determine the therapeutic agents that will be most effective in the ... Link to item Cite

Determination of comprehensive arterial blood inflow in abdominal-pelvic organs: Impact of respiration and posture on organ perfusion

Journal article Medical Science Monitor · January 1, 2011 Background: Arterial blood flow (BF) to all abdominal-pelvic organs (AP) shows potential for an indicator of comprehensive splanchnic organ circulation (reservoir of blood supply for redistribution) in cardiovascular disease, hepato-gastrointestinal diseas ... Full text Cite

Depletion of human regulatory T cells.

Journal article Methods Mol Biol · 2011 Regulatory T cells (Treg) have become increasingly relevant in the study of human disease including cancer. Treg cells have been shown to inhibit anti-tumor immune responses, and elevated Treg levels have been associated with certain types of cancer. Simil ... Full text Link to item Cite

Low-volume strength and endurance training prevent the decrease in exercise hyperemia induced by non-dominant forearm immobilization.

Journal article Eur J Appl Physiol · November 2010 We examined the effect of 3-week upper limb immobilization on conduit artery cross-sectional area and peak hyperemia (BF(peak)) after exhaustive dynamic handgrip exercise (Ex(dyn)), and that of low-volume strength and endurance training during immobilizati ... Full text Link to item Cite

CSPG4 protein as a new target for the antibody-based immunotherapy of triple-negative breast cancer.

Journal article J Natl Cancer Inst · October 6, 2010 BACKGROUND: The cell surface proteoglycan, chondroitin sulfate proteoglycan 4 (CSPG4), is a potential target for monoclonal antibody (mAb)-based immunotherapy for many types of cancer. The lack of effective therapy for triple-negative breast cancer (TNBC) ... Full text Link to item Cite

Ligand-independent toll-like receptor signals generated by ectopic overexpression of MyD88 generate local and systemic antitumor immunity.

Journal article Cancer Res · September 15, 2010 Although critical for initiating and regulating immune responses, the therapeutic use of individual cytokines as anticancer immunotherapeutic agents has achieved only modest clinical success. Consequently, many current strategies have focused on the use of ... Full text Link to item Cite

An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

Journal article J Clin Invest · September 2010 Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific ... Full text Open Access Link to item Cite

Synergism from combined immunologic and pharmacologic inhibition of HER2 in vivo.

Journal article Int J Cancer · June 15, 2010 The monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib improve the clinical outcome of patients with HER2-overexpressing breast cancer. However, the majority of metastatic cancers will eventually progress, suggesting the ... Full text Link to item Cite

Adenovirus vaccine immunotherapy targeting WT1-expressing tumors.

Journal article Expert Opin Biol Ther · June 2010 IMPORTANCE OF THE FIELD: Tumor associated antigens (TAAs) offer specific targets for developing cancer immunotherapies. In particular, viral vectors encoding transgenic TAAs have been used in recent vaccination strategies. Wilm's Tumor gene (WT1) is a robu ... Full text Link to item Cite

Abstract 5338: Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T cell killing mediated by CEA/CD3-bispecific T cell-engaging BiTE antibody

Journal article Cancer Research · April 15, 2010 AbstractCarcinoembryonic antigen (CEA; CD66e, CEACAM5) is a well-characterized tumor-associated antigen that is frequently and uniformly over-expressed in human carcinomas. A novel bispecific single-chain an ... Full text Cite

An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicty and enhanced therapeutic efficacy without oncogenicity.

Journal article Clin Cancer Res · March 1, 2010 PURPOSE: Overexpression of the breast cancer oncogene HER2 correlates with poor survival. Current HER2-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly HER2+, va ... Full text Link to item Cite

Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.

Journal article Br J Cancer · January 5, 2010 BACKGROUND: Novel technologies to redirect T-cell killing against cancer cells are emerging. We hypothesised that metastatic human colorectal cancer (CRC) previously treated with conventional chemotherapy would be sensitive to T-cell killing mediated by ca ... Full text Link to item Cite

Molecular characterization of putative chordoma cell lines.

Journal article Sarcoma · 2010 Immortal tumor cell lines are an important model system for cancer research, however, misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in ... Full text Link to item Cite

A study of passive weight-bearing lower limb exercise effects on local muscles and whole body oxidative metabolism: A comparison with simulated horse riding, bicycle, and walking exercise

Journal article Dynamic Medicine · December 31, 2009 Background: We have developed an exercise machine prototype for increasing exercise intensity by means of passively exercising lower limb muscles. The purpose of the present study was to compare the passive exercise intensity of our newly-developed machine ... Full text Cite

Low-volume muscle endurance training prevents decrease in muscle oxidative and endurance function during 21-day forearm immobilization.

Journal article Acta Physiol (Oxf) · December 2009 AIM: To examine the effects of low-volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21-day forearm immobilization (IMM-21d). METHODS: The non-dominant arm (n = 15) was immobilized for 21 day ... Full text Link to item Cite

Central command and the increase in middle cerebral artery blood flow velocity during static arm exercise in women.

Journal article Exp Physiol · November 2009 We examined the role of central command in static exercise-induced increase in middle cerebral artery mean blood flow velocity (V(MCA)). Eleven young female subjects performed static elbow flexion for 2 min at 30% maximal voluntary contraction without (con ... Full text Link to item Cite

Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity.

Journal article Cancer Gene Ther · September 2009 Recombinant serotype 5 adenovirus (Ad5) vectors lacking E1 expression induce robust immune responses against encoded transgenes in pre-clinical models, but have muted responses in human trials because of widespread pre-existing anti-adenovirus immunity. At ... Full text Link to item Cite

Physiology and therapeutics of vascular endothelial growth factor in tumor immunosuppression.

Journal article Curr Mol Med · August 2009 Vascular endothelial growth factor (VEGF), known as a primary mediator of tumor-induced angiogenesis, is now understood to have a role in tumor-associated immunosuppression. Initially, VEGF was identified to alter the growth and maturation of the immature ... Full text Link to item Cite

Hemodynamic relationships among upper-abdominal aorta and femoral arteries: basis for measurement of arterial blood flow to abdominal-pelvic organs.

Journal article Med Sci Monit · July 2009 BACKGROUND: Arterial blood flow (BF) to all abdominal-pelvic organs (AP) is a potentially useful indicator of splanchnic circulatory dysfunction or various stress-induced AP flow distributions. BFAP can be measured by subtracting BF in the "peripheral" bil ... Link to item Cite

Femoral artery blood flow and its relationship to spontaneous fluctuations in rhythmic thigh muscle workload.

Journal article Clin Physiol Funct Imaging · July 2009 BACKGROUND AND AIM: Limb femoral arterial blood flow (LBF) is known to increase linearly with increasing workload under steady-state conditions, suggesting a close link between LBF and metabolic activity. We, however, hypothesized that sudden physiological ... Full text Link to item Cite

Induction of Wilms' tumor protein (WT1)-specific antitumor immunity using a truncated WT1-expressing adenovirus vaccine.

Journal article Clin Cancer Res · April 15, 2009 PURPOSE: Wilms' tumor protein (WT1) is overexpressed in most leukemias and many solid tumors and is a promising target for tumor immunotherapy. WT1 peptide-based cancer vaccines have been reported but have limited application due to HLA restriction of the ... Full text Link to item Cite

Local increase in trapezius muscle oxygenation during and after acupuncture

Journal article Dynamic Medicine · April 13, 2009 Purpose. This study aimed to compare the trapezius muscle blood volume and oxygenation in the stimulation region and in a distant region in the same muscle during acupuncture stimulation (AS). We hypothesized that AS provokes a localized increase in muscle ... Full text Cite

Perceived exertion is not necessarily associated with altered brain activity during exercise.

Journal article J Physiol Anthropol · March 2009 Previous studies have investigated the relationship between prefrontal cortex activation and perceived exertion during prolonged exercise. However, the effect of perceived exertion on prefrontal cortex activity is confounded by exercise intensity. Therefor ... Full text Link to item Cite

The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients.

Journal article Cancer Immunol Immunother · August 2008 Impairment of dendritic cells (DC), the most effective activators of anticancer immune responses, is one mechanism for defective antitumor immunity, but the causes of DC impairment are incompletely understood. We evaluated the association of impaired DC di ... Full text Link to item Cite

Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines.

Journal article Blood · August 1, 2008 CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells limit antigen-specific immune responses and are a cause of suppressed anticancer immunity. In preclinical and clinical studies, we assessed the immune consequences of FoxP3(+) Treg-cell depletion in patien ... Full text Link to item Cite

Depletion of human regulatory T cells (Treg) and antigen-specific immune responses to cancer vaccines.

Journal article J Clin Oncol · May 20, 2008 3010 Background: CD4+CD25+FoxP3+ regulatory T cells (Treg) limit antigen-specific immune responses and are a cause of suppressed anticancer immunity. Conversely, depletion of Treg leads to immune enhancement. The immunotoxin denileukin diftitox which selec ... Link to item Cite

Low-volume muscular endurance and strength training during 3-week forearm immobilization was effective in preventing functional deterioration

Journal article Dynamic Medicine · March 7, 2008 Purpose. The purpose of this study was to determine whether endurance and strength hand grip exercises during 3-week upper limb immobilization preserve muscle oxidative capacity, endurance performance and strength. Methods. Ten healthy adult men underwent ... Full text Cite

Detailed analysis of cytomegalovirus (CMV)-specific T cells expanded for adoptive immunotherapy of CMV infection following allogeneic stem cell transplantation for malignant disease.

Journal article Cytotherapy · 2008 BACKGROUND: Cytomegalovirus (CMV) infection and its treatment causes significant morbidity following allogeneic stem cell transplantation (SCT) for malignancies. We studied the phenotype, function and growth kinetics of CMV pp65 antigen (Ag)-specific T cel ... Full text Link to item Cite

Apoptosis induction by p38 MAPK inhibitor in human colon cancer cells.

Journal article Hepatogastroenterology · 2008 BACKGROUND/AIMS: The p38 mitogen-activated protein kinases (p38 MAPKs) function in a wide variety of signaling pathways. However, the role of p38s is cell type- and stimulus-dependent. The present study aimed to evaluate the effects of p38 MAPK inhibitor o ... Link to item Cite

Epigallocatechin gallate affects human dendritic cell differentiation and maturation.

Journal article J Allergy Clin Immunol · January 2008 BACKGROUND: Epigallocatechin gallate (EGCG), a component of green tea catechin with the strongest biological activity, has been focused in recent years because of its anti-inflammatory and immunomodulatory activities. Dendritic cells (DCs) are professional ... Full text Link to item Cite

A study of dendritic and endothelial cell interactions in colon cancer in a cell line and small mammal model.

Journal article Eur J Surg Oncol · December 2007 AIM: Historically, cancer therapy directly targeting tumor cells have yielded suboptimal clinical results, and therefore anti-angiogenic therapy that targets tumor cells indirectly through impairing tumor vasculature is now considered to be one of the nove ... Full text Link to item Cite

Arterial blood flow of all abdominal-pelvic organs using Doppler ultrasound: range, variability and physiological impact.

Journal article Physiol Meas · October 2007 The pulsed Doppler method theoretically enables human arterial blood flow (BF) to be determined in all of the abdominal-pelvic organs (BF(AP)) by subtracting the bilateral proximal femoral arterial BF from the upper abdominal aorta BF above the coeliac tru ... Full text Link to item Cite

Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2.

Journal article J Transl Med · September 6, 2007 BACKGROUND: The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additi ... Full text Link to item Cite

Natural killer cell activation and dendritic cell-based vaccines

Journal article Minerva Biotecnologica · September 1, 2007 Natural killer (NK) cells are the key players of the innate immune system, which can immediately limit or eliminate dangerous challenges by pathogens or tumor cells to the host. Recent studies have demonstrated the reciprocal activation of NK cell and dend ... Cite

Immunotherapeutic targeting of Wilms' tumor protein.

Journal article Curr Opin Mol Ther · February 2007 The expression of Wilms' tumor protein (WT1)-derived peptides on malignant cell surfaces and recognition of those peptides by cellular and humoral immune responses suggest that WT1 may be a promising potential target antigen in immunotherapeutic trials. Wi ... Link to item Cite

Differences in exercising limb blood flow variability between cardiac and muscle contraction cycle related analysis during dynamic knee extensor.

Journal article J Sports Med Phys Fitness · December 2006 AIM: Blood flow in peripheral conduit arteries during steady-state, dynamic exercise, can be estimated noninvasively with Doppler ultrasound, by measuring the conduit arterial diameter and the mean blood velocity averaged over consecutive cardiac beat-by-b ... Link to item Cite

Recent clinical progress in virus-based therapies for cancer.

Journal article Expert Opin Biol Ther · November 2006 As our knowledge of the molecular basis of cancer expands, viral vectors have been increasingly studied as potential antitumour therapeutic agents. With their ability to invade and replicate within target cells, viruses have been utilised as oncolytic agen ... Full text Link to item Cite

Immunization with fowlpox vector-modified dendritic cell in patients with carcinoembryonic antigen-expressing cancer: Phase I clinical study

Journal article Biotherapy · November 1, 2006 A dendritic cell (DC), which can induce a primary immune response, is known to be the most potent antigen-presenting cell in the immune system. Many studies have been performed to evaluate the safety and efficacy of DC-based immunotherapy. At Duke Universi ... Cite

Impaired muscle oxygen metabolism in uremic children: improved after renal transplantation.

Journal article Am J Kidney Dis · September 2006 BACKGROUND: The purpose of this study is to clarify skeletal muscle oxidative metabolism in children with end-stage renal disease (ESRD) before and after renal transplantation. METHODS: We examined muscle oxygenation and metabolism by using noninvasive nea ... Full text Link to item Cite

NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity.

Journal article Cancer Immunol Immunother · September 2006 Recent reports revealed that dendritic cell (DC)-natural killer (NK) cell interaction plays an important role in tumor immunity, but few DC vaccine studies have attempted to evaluate the non-specific, yet potentially clinically relevant, NK response to imm ... Full text Link to item Cite

Age and activity status affect muscle reoxygenation time after maximal cycling exercise.

Journal article Med Sci Sports Exerc · July 2006 PURPOSE: The purpose of this study was to determine the interaction of age and habitual physical activity on recovery time of muscle oxygenation following maximal cycling exercise (CycEXmax). METHODS: Twelve sedentary middle-aged (50+/-6), 13 sedentary eld ... Full text Link to item Cite

Alterations in the blood velocity profile influence the blood flow response during muscle contractions and relaxations.

Journal article J Physiol Sci · June 2006 The present study examined the influences of the muscle contraction (MCP) and relaxation (MRP) phases, as well as systole and diastole, on the blood velocity profile and flow in the conduit artery at different dynamic muscle contraction forces. Eight healt ... Full text Link to item Cite

Early-outgrowth of endothelial progenitor cells can function as antigen-presenting cells.

Journal article Cancer Immunol Immunother · June 2006 Endothelial progenitor cells (EPCs) have been recently found to exist circulating in peripheral blood of adults, and home to sites of neovascularization in peripheral tissues. They can also be differentiated from peripheral blood mononuclear cells (PBMNCs) ... Full text Link to item Cite

Role of natural killer cell function in dendritic cell-based vaccines.

Journal article Expert Rev Vaccines · February 2006 Recent studies have elucidated the functional links between natural killer (NK) cells and, demonstrating the reciprocal activation of these cell types through NK-DC interactions. The subsets of cells and molecular pathways involved in such interactions hav ... Full text Link to item Cite

Dendritic cell-based immunotherapy.

Journal article Int Rev Immunol · 2006 Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publi ... Full text Link to item Cite

Sulforaphane induces inhibition of human umbilical vein endothelial cells proliferation by apoptosis.

Journal article Angiogenesis · 2006 Sulforaphane (SUL), one of the isothiocyanates (ITCs), has recently been focused due to its inhibitory effects on tumor cell growth in vitro and in vivo, which is dependent on the direct effect on cancer cells. In the present study, we aimed to investigate ... Full text Link to item Cite

Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer.

Journal article Cancer Sci · November 2005 Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical ... Full text Link to item Cite

Ex vivo expanded human CD4+ regulatory NKT cells suppress expansion of tumor antigen-specific CTLs.

Journal article Int Immunol · September 2005 NKT cells can produce large amounts of both Th1- and Th2-type cytokines and are an important regulatory cell type. To elucidate their role in acquired immunity, we examined the effect of human Valpha24+Vbeta11+ NKT cells or CD1d-specific ligand alpha-galac ... Full text Link to item Cite

Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise.

Journal article Metabolism · August 2005 In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabo ... Full text Link to item Cite

CD11b-mediated migratory property of peripheral blood B cells.

Journal article J Allergy Clin Immunol · July 2005 BACKGROUND: CD11b belongs to the integrin family and is expressed on neutrophils, monocytes, natural killer cells, and a subset of lymphocytes. Although CD11b expressed on neutrophils and monocytes has been extensively investigated and has been reported to ... Full text Link to item Cite

Correlation of clinical outcome with natural killer (NK) response to an anti-cancer, dendritic cell-based vaccine.

Journal article J Clin Oncol · June 2005 2585 Background: Cancer vaccines have generally been developed to activate antigen-specific T cell responses, but few studies have attempted to evaluate the non-specific, yet potentially clinically-relevant, NK response to immunization. We hypothesized tha ... Link to item Cite

Effects of blackcurrant anthocyanin intake on peripheral muscle circulation during typing work in humans.

Journal article Eur J Appl Physiol · May 2005 This double-blind, placebo-controlled, crossover study investigated the effect of blackcurrant anthocyanin (BCA) intake on peripheral circulation during rest and during typing work by using near-infrared spectroscopy (NIRS), and it also assessed improvemen ... Full text Link to item Cite

Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules.

Journal article Clin Cancer Res · April 15, 2005 PURPOSE: To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen. EXPERIMENTAL DESIGN: In this phase I study, we administered one or two cycles of four tri ... Full text Link to item Cite

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.

Journal article J Transl Med · February 21, 2005 BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of a ... Full text Link to item Cite

Alterations in the rheological flow profile in conduit femoral artery during rhythmic thigh muscle contractions in humans.

Journal article Jpn J Physiol · February 2005 The present study examined the rheological blood velocity profile in the conduit femoral artery during rhythmic muscle contractions at different muscle forces. Eight healthy volunteers performed one-legged, dynamic knee-extensor exercise at work rates of 5 ... Full text Link to item Cite

Enumerating antigen-specific T-cell responses in peripheral blood: a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis.

Journal article J Immunother · 2005 Detection of the circulating antigen-specific T-cell response to immunization is an important biologic end point in clinical trials of cancer vaccines. Typically employed assays are peptide MHC tetramer, ELISpot, and intracellular cytokine analysis. Althou ... Full text Link to item Cite

Flt3-ligand as a vaccine adjuvant: Results in a study of Flt3-ligand plus tetanus toxoid immunization

Journal article Journal of Applied Research · December 1, 2004 Dendritic cells (DC) efficiently process and present antigens to the effector arm of the immune system, thereby stimulating immunity against antigens of both foreign and self origin. Administration of Flt3-ligand (FL) has been reported to increase dendriti ... Cite

Exercise-related time course of pulsatility index in brachial artery following forearm exercise assessed by Doppler ultrasound.

Journal article Tohoku J Exp Med · August 2004 At rest, vascular reactivity assessed by the changes in pulsatility index (PI) is one indicator of vessel stenosis in some clinical/basic science research. However, all types of vessel stenosis do not show an alteration in the PI, because flow perfusion ma ... Full text Link to item Cite

Regulatory and effector T cell subsets and dendritic cells in breast cancer.

Journal article J Clin Oncol · July 15, 2004 9697 Background: Successful immune responses against breast cancer may depend on the balance between immune stimulation mediated through dendritic cells (DC) & cytolytic T cells, and immune inhibition mediated in part by CD4+CD25+ regulatory T cells (Treg) ... Link to item Cite

Phase I study of immunization with dendritic cells (DC) modified with recombinant fowlpox encoding carcinoembryonic antigen (CEA) and the triad of costimulatory molecules CD54, CD58, and CD80 (rF-CEA(6D)-TRICOM) in patients with advanced malignancies.

Journal article J Clin Oncol · July 15, 2004 2508 Background: We hypothesize that the activity of vaccines based on DC loaded with tumor antigens will be enhanced by modifications that increase antigen expression and costimulatory activity of the DC. METHODS: In an ongoing phase I study, we are admin ... Link to item Cite

Tumor-infiltrating effector cells of alpha-galactosylceramide-induced antitumor immunity in metastatic liver tumor.

Journal article J Immune Based Ther Vaccines · July 13, 2004 BACKGROUND: alpha-Galactosylceramide (alpha-GalCer) can be presented by CD1d molecules of antigen-presenting cells, and is known to induce a potent NKT cell-dependent cytotoxic response against tumor cells. However, the main effector cells in alpha-GalCer- ... Full text Link to item Cite

Muscle contraction-induced limb blood flow variability during dynamic knee extensor.

Journal article Med Sci Sports Exerc · July 2004 PURPOSE: To evaluate whether muscle contraction-induced variability of limb femoral arterial blood flow (FABF) can be reduced with longer sampling durations. This was assessed in relation to muscle contraction-relaxation cycles (CRcycles) during steady-sta ... Full text Link to item Cite

Brain and central haemodynamics and oxygenation during maximal exercise in humans.

Journal article J Physiol · May 15, 2004 During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O(2) delivery and uptake. Here, we examined whether the uptake of O(2) and substrates by the human brain is compromised and whether the fall in ... Full text Link to item Cite

Noninvasive monitoring of deterioration in skeletal muscle function with forearm cast immobilization and the prevention of deterioration

Journal article Dynamic Medicine · February 6, 2004 Background: In this research inactivity was simulated by immobilizing the forearm region in a plaster cast. Changes in skeletal muscle oxidative function were measured using near-infrared spectroscopy (NIRS), and the preventative effect of the training pro ... Cite

Does the aging skeletal muscle maintain its endocrine function?

Journal article Exerc Immunol Rev · 2004 Contracting skeletal muscles produce and release the cytokine interleukin (IL)-6 and this release is augmented by the presence of low muscle glycogen. Since muscle metabolism in elderly subjects relies on glycogen more than younger subjects, it is possible ... Link to item Cite

Post-exercise hyperemia after ischemic and non-ischemic isometric handgrip exercise.

Journal article J Physiol Anthropol Appl Human Sci · November 2003 Post-exercise related time course of muscle oxygenation during recovery provides valuable information on peripheral vascular disease. The purpose of the present study was to examine post-exercise hyperemia (forearm blood flow; FBF, Doppler ultrasound) asse ... Full text Link to item Cite

Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans.

Journal article J Physiol · April 15, 2003 The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 heal ... Full text Link to item Cite

Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans.

Journal article J Physiol · January 1, 2003 Previous studies show that exercise-induced hyperaemia is unaffected by systemic inhibition of nitric oxide synthase (NOS) and it has been proposed that this may be due to compensation by other vasodilators. We studied the involvement of cytochrome P450 2C ... Full text Link to item Cite

IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle.

Journal article Am J Physiol Endocrinol Metab · December 2002 The aim of the present study was to examine whether IL-6 and TNF-alpha are expressed in, and released from, human skeletal muscle during exercise. We hypothesized that the skeletal muscle will release IL-6, but not TNF-alpha, during exercise because of pre ... Full text Link to item Cite

Blood flow and oxygen uptake increase with total power during five different knee-extension contraction rates.

Journal article J Appl Physiol (1985) · November 2002 Controversies exist regarding quantification of internal power (IP) generated by the muscles to overcome energy changes of moving body segments when external power (EP) is performed. The aim was to 1) use a kinematic model for estimation of IP during knee ... Full text Link to item Cite

Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation.

Journal article J Physiol · May 15, 2002 There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycoge ... Full text Link to item Cite

Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle.

Journal article J Physiol · April 1, 2002 The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein durin ... Full text Link to item Cite

Quantitative effects of respiration on venous return during single knee extension-flexion.

Journal article Int J Sports Med · April 2002 Respiration and the muscle pump play major roles in increasing venous return. However, the relative contribution of each of these factors remains unclear. The present study investigates the quantitative effects of interaction between respiration and the mu ... Full text Link to item Cite

Femoral artery inflow in relation to external and total work rate at different knee extensor contraction rates.

Journal article J Appl Physiol (1985) · March 2002 Whether limb blood flow is directly regulated to match the work rate, independent of the rate of contraction, remains elusive. This study therefore investigated the relationship between femoral arterial blood flow (FABF; Doppler ultrasound) and "external" ... Full text Link to item Cite

Cholesterol granuloma of the breast mimicking carcinoma: report of a case.

Journal article Surg Today · 2002 Cholesterol granuloma of the breast is a rare benign condition which is often clinically and radiologically indistinguishable from breast carcinoma. We herein report the case of a 62-year-old asymptomatic woman who was found on a routine breast examination ... Full text Link to item Cite

Decreased synthesis of matrix metalloproteinase-7 and adhesion to the extracellular matrix proteins of human colon cancer cells treated with troglitazone.

Journal article Surg Today · 2002 PURPOSE: In the present study, we investigated the effect of troglitazone, a selective ligand and agonist of PPAR-gamma, on the metastatic potential of human colon cancer cells. METHODS: High- and low-PPAR-gamma expression clones of the colon cancer cell l ... Full text Link to item Cite

Dendritic cells cultured in anti-CD40 antibody-immobilized plates elicit a highly efficient peptide-specific T-cell response.

Journal article J Immunother · 2002 The function of dendritic cells (DCs), antigen-presenting cells that can initiate and regulate cellular and humoral responses, is highly influenced by their level of maturation. Immature DCs may be harmful in anti-tumor immunotherapy, because they can indu ... Full text Link to item Cite

Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content.

Journal article J Physiol · December 1, 2001 1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from c ... Full text Link to item Cite

Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content.

Journal article FASEB J · December 2001 In humans, the plasma interleukin 6 (IL-6) concentration increases dramatically during low-intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability inf ... Full text Link to item Cite

Peripheral blood dendritic cells, but not monocyte-derived dendritic cells, can augment human NK cell function.

Journal article Cell Immunol · October 10, 2001 Dendritic cells (DCs) are essential antigen-presenting cells with a wide variety of functions relating to both adaptive and innate immunity. Recently, interactions of DCs with natural killer (NK) cells and NK1.1-positive T cells have been reported in mice. ... Full text Link to item Cite

Clustered cancer cells show a distinct adhesion behavior from single cell form under physiological shear conditions.

Journal article J Exp Clin Cancer Res · September 2001 It remains a question whether hematogeneous metastasis arises from a single cancer cell attached to the local endothelium or from a cluster of cancer cells trapped in the vascular bed in the target organ. Adhesive interaction of the single cell form and th ... Link to item Cite

Dendritic cells activate antitumor immunity for malignant intracranial germ cell tumor: a case report.

Journal article Jpn J Clin Oncol · August 2001 We report a 22-year-old male patient with a history of intracranial malignant germ cell tumor (GCT) who had undergone tumor resection twice, followed by radiation and chemotherapy. The tumor had rapidly recurred along the entire ventricular wall with exten ... Full text Link to item Cite

Thoracic empyema associated with recurrent colon cancer: report of a case and review of the literature.

Journal article Dis Colon Rectum · February 2001 Many types of infections associated with colorectal cancer have been reported. Here, we describe a rare case of thoracic empyema that was observed during immunotherapy for recurrent colon cancer. Culture of the pleural fluid yielded Streptococcus bovis, wh ... Full text Link to item Cite

Reoxygenation rate immediately after static short-term high intensity exercise indicates muscle oxidative capacity

Journal article Applied Cardiopulmonary Pathophysiology · December 1, 2000 The purpose of this study was to determine whether the reoxygenation rate (Reoxy-rate) immediately after static exercise at various submaximal intensities could indicate the muscle oxidative capacity. Seven healthy male subjects performed a static hand gri ... Cite

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.

Journal article J Physiol · November 15, 2000 1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such ... Full text Link to item Cite

Effects of epinephrine and lactate on the increase in oxygen consumption of nonexercising skeletal muscle after aerobic exercise.

Journal article J Biomed Opt · October 2000 The purpose of this study was to measure O2 consumption of nonexercising skeletal muscles (VO2nonex) at rest and after aerobic exercise and to investigate the stimulant factors of O2 consumption. In experiment 1, we measured the resting metabolic rate of t ... Full text Link to item Cite

Alpha-glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes obtained from cancer patients by activating CD3-CD56+ NK cells in vitro.

Journal article J Immunol · August 1, 2000 Alpha-glycosylceramides, such as alpha-galactosylceramide and alpha-glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, V alpha 14 TCR+NK1.1+ T cells, which accumulate preferentially in the l ... Full text Link to item Cite

Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma.

Journal article J Hepatol · August 2000 BACKGROUND/AIMS: Glutamine synthetase (GS) catalyzes the synthesis of glutamine, a major energy source of cells, and is upregulated in a subset of human hepatocellular carcinomas (HCCs). GS expression may be related to tumor recurrence, since GS-expressing ... Full text Link to item Cite

Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer.

Journal article Br J Cancer · August 2000 Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two isoforms of COX, COX-1 and ... Full text Link to item Cite

Quantification of ischemic muscle deoxygenation by near infrared time-resolved spectroscopy.

Journal article J Biomed Opt · January 2000 The purpose of this study was to quantify muscle deoxygenation in human skeletal muscles using near infrared time-resolved spectroscopy (NIRTRS) and compare NIRTRS indicators and blood saturation. The forearm muscles of five healthy males (aged 27-32 yrs.) ... Full text Link to item Cite

Expression of platelet-derived endothelial cell growth factor correlates with good prognosis in patients with colorectal carcinoma.

Journal article Cancer · January 1, 2000 BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that has potent chemotactic activity for endothelial cells. Although it is expressed in the majority of colorectal tumors, and some reports suggest that its high ... Link to item Cite

MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer.

Journal article Oncologist · 2000 BACKGROUND: Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. MMP-1 is a member of collagenases, a family of MMPs that de ... Full text Link to item Cite

E-selectin can mediate the arrest type of adhesion of colon cancer cells under physiological shear flow.

Journal article Eur J Cancer · January 2000 The aim of this study was to determine whether colon cancer cells flowing in blood exhibit the same adhesion pattern to the vascular bed as leucocytes using a flow adhesion system. In shear flow conditions, five colon cancer cell lines showed less tetherin ... Full text Link to item Cite

Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522.

Journal article Br J Cancer · December 1999 It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characte ... Full text Link to item Cite

Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow.

Journal article Br J Cancer · August 1999 Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous pres ... Full text Link to item Cite

CD8(+)NKR-P1A (+)T cells preferentially accumulate in human liver.

Journal article Eur J Immunol · August 1999 A unique subset of T cells that co-express NKR-P1, which is a lectin type of NK receptor and is thought to have a major role in triggering NK activity, has been identified. In mice, NK1.1 (mouse NKR-P1C)(+) T cells, called NKT cells, preferentially accumul ... Full text Link to item Cite

Histopathological prognostic factors influencing long-term prognosis after surgical resection for hepatic metastases from colorectal cancer.

Journal article Am J Gastroenterol · March 1999 OBJECTIVE: We aimed to present new histopathological features of metastatic liver nodules as more reliable prognostic factors after surgical resection for colorectal metastatic cancer. METHODS: Clinicopathological features, including newly proposed histopa ... Full text Link to item Cite

Acquisition of glutamine synthetase expression in human hepatocarcinogenesis: relation to disease recurrence and possible regulation by ubiquitin-dependent proteolysis.

Journal article Cancer · February 15, 1999 BACKGROUND: The authors previously reported increased ubiquitin (Ub) immunoreactivity in hepatocellular carcinomas (HCCs) and suggested a possible correlation between changes in ubiquitinated protein levels and multistep hepatocarcinogenesis. The current s ... Full text Link to item Cite

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension.

Journal article J Appl Physiol (1985) · February 1999 The redistribution of blood flow (BF) in the abdominal viscera during right-legged knee extension-flexion exercise at very low intensity [peak heart rate (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting, subjects performed a righ ... Full text Link to item Cite

Increased ubiquitin immunoreactivity in hepatocellular carcinomas and precancerous lesions of the liver.

Journal article J Hepatol · June 1997 BACKGROUND/AIMS: Ubiquitin covalently attaches to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tu ... Full text Link to item Cite

Immunoreaction at 43 kDa with anti-ubiquitin antibody in breast neoplasms.

Journal article Jpn J Cancer Res · March 1997 Protein ubiquitination has been implicated in ATP-dependent protein turnover and normal cell proliferation. To investigate whether the ubiquitin-mediated system is functionally involved in the cancerous state, we examined changes in protein ubiquitination ... Full text Link to item Cite

E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma.

Journal article Hepatology · December 1996 In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM ... Full text Link to item Cite

Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy.

Journal article J Appl Physiol (1985) · September 1996 The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metaboli ... Full text Link to item Cite

Human colorectal carcinomas specifically accumulate Mr 42,000 ubiquitin-conjugated cytokeratin 8 fragments.

Journal article Cancer Res · June 15, 1996 Recent studies have shown that various tumor cells accumulate ubiquitin (Ub)-conjugated proteins, the profiles of which differ from those of normal cells. To identify the Ub-conjugated proteins accumulated specifically by human carcinoma cells, a two-dimen ... Link to item Cite

Surgical resection for small hepatocellular carcinoma.

Journal article Surgery · January 1996 BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) can be curative in selected patients, particularly in those with a solitary small HCC (s-sHCC; 2 cm or less in diameter). However, even these patients often have a risk of tumor recurrence o ... Full text Link to item Cite