elastin and Head-and-Neck-Neoplasms

<br><b>Introduction:</b> Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.</br> <br><b>Aim:</b> The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.</br> <br><b>Material and methods:</b> The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.</br> <br><b>Results</b>: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.</br> <br><b>Conclusions:</b> The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.</br>.

Topics: Connective Tissue; Elastin; Head and Neck Neoplasms; Humans; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9

Dermatofibrosarcoma protuberans (DFSP) is a locally invasive neoplasia with a pattern of infiltrative growth that leads to extended resections. To avoid unnecessary resections and spare tissues, its treatment requires an adequate assessment of the margins. We present a case where artificial dermis (Matriderm®) was used followed by skin graft for reconstruction. We present a 50-year-old woman with a DFSP in the occipital region. She was referred to us after a first surgery with positive margins. A wide local excision with a 2-cm margin was performed and periosteal tissue was also removed, which led to exposure of the skull. Matriderm was placed on the bone surface and dressings were changed every other day. Meanwhile, margins were evaluated by the complete circumferential and peripheral deep margin assessment (CCPDMA) and were positive for DFSP in the superior margin. After 4 weeks the area was completely covered by granulation tissue and a new resection followed by reconstruction with a skin graft was performed. With regard to the difficulties in the margin assessment in DFSP, we present artificial dermis (Matriderm) as an option for reconstructive surgery in these patients, especially when a skin graft cannot be performed as a first option.

Topics: Collagen; Dermatofibrosarcoma; Elastin; Female; Head and Neck Neoplasms; Humans; Middle Aged; Scalp; Skin Neoplasms; Skin Transplantation; Skin, Artificial

Silk-elastinlike protein polymers (SELPs) have been effectively used as controlled release matrices for the delivery of viruses for cancer gene therapy in preclinical models. However, the degradability of these polymers needs to be tuned for improved localized intratumoral gene delivery. Using recombinant techniques, systematic modifications in distinct regions of the polymer backbone, namely, within the elastin blocks, silk blocks, and adjacent to silk and elastin blocks, have been made to impart sensitivity to specific matrix metalloproteinases (MMPs) known to be overexpressed in the tumor environment. In this report we investigated the structure-function relationship of MMP-responsive SELPs for viral mediated gene therapy of head and neck cancer. These polymers showed significant degradation in vitro in the presence of MMPs. Their degradation rate was a function of the location of the MMP-responsive sequence in the polymer backbone when in hydrogel form. Treatment efficacy of the adenoviral vectors released from the MMP responsive SELP analogs in a xenograft mouse model of head and neck squamous cell carcinoma (HNSCC) was shown to be polymer structure dependent. These results demonstrate the tunable nature of MMP-responsive SELPs for localized matrix-mediated gene delivery.

Topics: Adenoviridae; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Delayed-Action Preparations; Elastin; Female; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Head and Neck Neoplasms; Humans; Matrix Metalloproteinases; Mice, Nude; Silk; Squamous Cell Carcinoma of Head and Neck

In oncology, dermal equivalent may be indicated to cover losses of substance related to skin tumors or after the removal of skin flaps.. To report our experience of two dermal equivalents, Matriderm 1 mm with a one-stage graft (DE1) and Integra DL with a two-stage graft (DE2) in oncology.. Retrospective, single-center study involving 16 patients.. Sixteen patients received dermal equivalents as an alternative to flaps (7 cases), over tendinous areas (7 cases), and for cosmetic purposes (2 cases). Twelve patients received DE1 and four DE2. Wound healing times with DE1 were 4 weeks less than those with DE2. Three cases of infection were noted with DE2. The use of dermal equivalents as an alternative to skin flaps was effective, and no adhesions were found over the tendinous areas.. The learning curve, the two-stage graft required with DE2, and not using a vacuum-assisted closure system can explain the high infection rate. The use of dermal equivalents is particularly indicated in the treatment of skin defect in oncology. The possibility of a one-stage graft with DE1 and combination with negative pressure therapy is beneficial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Collagen; Elastin; Head and Neck Neoplasms; Humans; Middle Aged; Otorhinolaryngologic Neoplasms; Plastic Surgery Procedures; Retrospective Studies; Skin Neoplasms; Skin Transplantation; Skin, Artificial; Surgical Flaps; Surgical Wound Infection; Time Factors; Wound Healing; Young Adult

The silk-elastinlike protein polymer, SELP 815K, and poloxomer 407, a commercially available synthetic copolymer, were evaluated to compare their relative performance in matrix-mediated viral gene delivery. Using a xenogenic mouse tumor model of human head and neck squamous cell carcinoma, the efficacy of viral gene-directed enzyme prodrug therapy with these polymers was characterized by viral gene expression in the tumor tissue, tumor size reduction, and survivability with treatment. Viral injection in SELP 815K produced a greater level and more prolonged extent of gene expression in the tumor, a statistically greater tumor size reduction, a longer time until tumor rebound, and a significantly increased survivability, as compared to injection of virus alone or in Poloxamer 407. Safety of treatment with these polymers was evaluated in a non-tumor bearing immunocompetent mouse model. Compared to virus injected alone or in Poloxamer 407, virus injected in SELP 815K had fewer and less severe indications of toxicity related to treatment as assessed by blood analysis, body weight, and histopathology of distant organs and the injection sites. Similar to virus alone or in Poloxamer 407, virus injected in SELP 815K elicited a mild injection site inflammatory response characterized primarily by a mononuclear leukocyte infiltrate and the formation of granulation tissue. Virus injected in SELP 815K resulted in fewer animals with elevated white blood cell counts and a less pronounced local toxicity reaction than was observed with virus in Poloxamer 407. In contrast to virus injected alone or in Poloxamer 407, which were not retained in the injection site tissues beyond week 1, SELP 815K was retained at the injection sites and by the end of the study (week 12), displayed limited absorption, and mild encapsulation. These results demonstrate the benefits of SELP 815K for matrix-mediated gene delivery over the injection of free virus and the injection of virus in Poloxamer 407. Virus in SELP 815K had greater efficacy of tumor suppression, promoted greater levels and greater duration of viral gene expression, and displayed reduced levels of injection site toxicity. Combining these performance and safety benefits with the degree of control with which they can be designed, synthesized and formulated, SELPs continue to show promise for their application in viral gene delivery.

Topics: Adenoviridae; Animals; Blood Chemical Analysis; Elastin; Female; Ganciclovir; Gene Transfer Techniques; Genetic Therapy; Head and Neck Neoplasms; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Mice; Mice, Nude; Poloxamer; Prodrugs; Proteins; Silk; Treatment Outcome; Xenograft Model Antitumor Assays

Silk-elastinlike protein polymers (SELP's) are block copolymers of silk-like and elastin-like tandem repeats. With appropriate sequence and composition SELPs can be liquid at room temperature and form hydrogels at body temperature. The influence of polymer structure and concentration on biodegradation in vitro and controlled delivery of adenoviruses carrying reporter genes to head and neck tumors in vivo was evaluated using hydrogels made from three SELP analogs. SELP-815K, with eight silk and fifteen elastin units and a lysine (K) modified elastin, was compared to SELP-415K and SELP-47K. Hydrogels with higher silk content and concentration degraded at a slower rate compared to other analogs. Intratumoral injection of adenoviruses with SELPs enhanced gene expression in tumor tissue up to 10 fold compared to viral injection without polymer. Viruses delivered with SELP-815K at 4 wt.% polymer concentration showed the highest level of gene expression. Tumor to liver ratio of expression was up to 55 fold higher for SELP-mediated systems. This study demonstrates the influence of exquisite control over polymer structure using recombinant techniques on spatial and temporal control over adenoviral delivery and establishes the utility of SELP matrices as biodegradable systems for gene therapy of head and neck cancer.

Topics: Adenoviridae; Amino Acid Sequence; Animals; beta-Galactosidase; Cross-Linking Reagents; Elastin; Gene Expression; Genetic Therapy; Head and Neck Neoplasms; Humans; Hydrogels; Lac Operon; Luminescence; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Transplantation; Recombinant Proteins; Silk; Structure-Activity Relationship