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1.
Clin Cancer Res ; 20(16): 4289-301, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-24944316

ABSTRACT

PURPOSE: How tumors evade or suppress immune surveillance is a key question in cancer research, and overcoming immune escape is a major goal for lengthening remission after cancer treatment. Here, we used the papillomavirus-associated rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer, to reveal the mechanisms underlying the antitumorigenic effects of intraperitoneal oxidative stress following O3/O2-pneumoperitoneum (O3/O2-PP) treatment. EXPERIMENTAL DESIGN: Solid auricular VX2 tumors were induced in immune-competent adult New Zealand White Rabbits. Animals were O3/O2-PP- or sham-treated, after which they underwent tumor ablation upon reaching no-go criteria. CD3(+) tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry, and expression levels of 84 immune response genes were measured by quantitative real-time PCR. Adoptive transfer of peripheral blood leukocytes (PBL)-derived from animals with tumor regression-into control animals with progressing tumors was implemented to assess acquired tumor resistance functionally. RESULTS: Auricular VX2 tumors regressing after O3/O2-PP treatment exhibited increased levels of CD3(+) TILs; they also exhibited enhanced expression of genes that encode receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with regressing tumors to recipient rabbits with newly implanted VX2 carcinoma resulted in acquired tumor resistance of the host and tumor regression. CONCLUSION: Intraperitoneal oxidative stress effectively converts the immune response against the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to tumoricidal and leads to a sustainable, adoptively transferable oncolytic immune response.


Subject(s)
Head and Neck Neoplasms/prevention & control , Lung Neoplasms/prevention & control , Lymphocytes, Tumor-Infiltrating/immunology , Oxidative Stress , Oxygen/therapeutic use , Ozone/therapeutic use , Papillomaviridae/immunology , Adoptive Transfer , Animals , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/prevention & control , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/metabolism , Humans , Immunoenzyme Techniques , Immunotherapy, Adoptive , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Lymphocyte Activation , Male , Pneumoperitoneum/immunology , RNA, Messenger/genetics , Rabbits , Real-Time Polymerase Chain Reaction , Remission Induction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
2.
Acta Otolaryngol ; 134(1): 100-4, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24256034

ABSTRACT

CONCLUSION: Feasibility of intraoperative 3D imaging with freehand (fh) SPECT for sentinel lymph node (SLN) biopsy in head and neck cancer (HNC) could be demonstrated. Controlled clinical studies are needed to evaluate its accuracy and impact on patient morbidity. OBJECTIVES: The clinical N0 neck in HNC needs improvement in management to sufficiently detect occult neck disease but to spare patients from potential morbidity by elective neck dissection. The SLN concept has potential to accurately stage the neck with low morbidity. METHODS: fhSPECT is a 3D tomographic imaging modality with a gamma probe system combined with an infrared optical tracking system. Five patients with HNC and clinical N0 neck were recruited. Scanning for SLN using fhSPECT was performed before excision and selective neck dissection and specimens were analyzed histopathologically. RESULTS: Preoperatively, a total of nine SLNs were located in five patients with fhSPECT. SLNs in three patients were positive for metastatic disease; in two patients the SLNs were tumor-free. No residual radioactivity was found in the neck in any of the patients after extirpation of SLNs. fhSPECT acquisitions took 2.6 ± 0.4 min. No metastatic lymph nodes were detected in any other node harvested during subsequent selective neck dissection in any patients.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Lymph Nodes/diagnostic imaging , Adult , Aged , Feasibility Studies , Female , Humans , Intraoperative Care , Lymphatic Metastasis , Male , Middle Aged , Sentinel Lymph Node Biopsy , Tomography, Emission-Computed, Single-Photon
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