generation-novel-dendritic-cell-vaccine-using-melanoma-squamous

Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

We identified cancer stem cell (CSC)-enriched populations from murine melanoma D5 syngeneic to C57BL/6 mice and the squamous cancer SCC7 syngeneic to C3H ...

University of Michigan

Dedifferentiated liposarcoma of the cheek: case report and literature review.

Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy.

Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer.

Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach.

Prevention of wound complications following salvage laryngectomy using free vascularized tissue.

Appropriate treatment of head and neck squamous cell cancer (HNSCC) remains one of the most difficult challenges in head and neck oncology. Overall survival of patients with HNSCC remains at approximately 50% at 5 years. Surgical therapy can be mutilating and often has significant effects on swallowing, speech, and physical appearance. The addition of chemotherapy to radiation treatment has shown efficacy in organ preservation in some sites in the head and neck, but has resulted in limited improvement in survival rates. HNSCC resistance to chemotherapy has limited the usefulness of chemotherapy in the treatment of this disease. We have recently demonstrated that human head and neck squamous cell cancers contain a tumorigenic, so-called cancer stem cell, subpopulation of cells that can self-renew and produce differentiated cells that form the bulk of the tumor. These tumorigenic HNSCC cells have a distinct phenotype and can be identified by a surface marker. Current treatment for HNSCC regimens may selectively kill the differentiated cancer cells, producing tumor regression while sparing the cancer stem cells, leading to tumor regrowth and relapse. It is important for us to understand why HNSCC does not respond to chemotherapy and to identify new targeted treatments that can overcome resistance and improve patient outcomes. Further study of HNSCC stem cells will increase our knowledge of this devastating disease and allow us to develop novel treatments.

Cancer stem cells in head and neck squamous cell cancer.

Extensive skin, paranasal, and skull base malignancies often invade the orbit necessitating the removal of the orbital contents to achieve local tumor control. Defects of this region often create a communication between the intracranial and extracranial contents that involves a large volume of skin, soft tissue, and bone. Local and regional tissue alone is rarely adequate to repair these defects. In contrast, free tissue transfer can provide vascularized skin, soft tissue, and bone that can reliably separate the extracranial and intracranial compartments and restore the bony and soft tissue architecture of the orbitomaxillary complex. This article summarizes the approach to orbitomaxillary reconstruction and discusses the use of free tissue transfer in the rehabilitation of this complex region.

Microvascular reconstruction of the orbital complex.

to design in vitro and in vivo models of metastasis to study the behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).

Metastatic potential of cancer stem cells in head and neck squamous cell carcinoma.

To determine whether a novel small molecule inhibitor derived from curcumin (FLLL32) that targets signal transducer and activator of transcription (STAT) 3 would induce cytotoxic effects in STAT3-dependent head and neck squamous cell cancer (HNSCC) cells and would sensitize tumors to cisplatin.

Sensitization of head and neck cancer to cisplatin through the use of a novel curcumin analog.

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(-) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(-) cell lines. Differentially methylated loci between HPV(+) and HPV(-) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(-) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(-) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(-) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.

Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis.

To determine if the various imaging modalities for distant metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma (HNSCC).

Diagnostic modalities for distant metastasis in head and neck squamous cell carcinoma: are we changing life expectancy?

Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of CSCs. In this study, we examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity. Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to CSCs, resulting in CSC lysis in the presence of complement. CTLs generated from peripheral blood mononuclear cells or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring antitumor immunity. Together, these proof-of-concept results provide a rationale for a new type of cancer immunotherapy based on the development of CSC vaccines that can specifically target CSCs.

Cancer stem cell vaccination confers significant antitumor immunity.

Head and neck squamous cell carcinomas (HNSCCs) have devastating morbidity rates with mortality mainly because of metastasis.

In vitro cytokine release profile: predictive value for metastatic potential in head and neck squamous cell carcinomas.

Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols.

Weekly chemotherapy with radiation versus high-dose cisplatin with radiation as organ preservation for patients with HPV-positive and HPV-negative locally advanced squamous cell carcinoma of the oropharynx.

Residents make their lists and program directors check them twice: reviewing case logs.

To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial.

Mark E.P. Prince

Department of Otolaryngology

University of Michigan

Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Mark E.P. Prince

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University of Michigan

Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Department of Otolaryngology