T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1+ and Vδ2+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.
21 September 2015 in Analytical Cellular Pathology
Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.
In the last years, propeller flaps have become an appealing option for coverage of a large range of defects. Besides having a more reliable vascular pedicle than traditional flap, propeller flaps allow for great freedom in design and for wide mobilization that extend the possibility of reconstructing difficult wounds with local tissues and minimal donor-site morbidity. They also allow one-stage reconstruction of defects that usually require multiple procedures. Harvesting of a propeller flap requires accurate patient selection, preoperative planning, and dissection technique. Complication rate can be kept low, provided that potential problems are prevented, promptly recognized, and adequately treated. This paper reviews current knowledge on propeller flaps. Definition, classification, and indications in the different body regions are discussed based on a review of the literature and on the authors’ experience. Details about surgical technique are provided, together with tips to avoid and manage complications.
1 May 2012 in Journal of Plastic, Reconstructive & Aesthetic Surgery
Background: The vastus lateralis muscle is a versatile donor site for pedicled and free flaps that, despite great potential, remains unpopular. Although the muscle is classically described as a single belly, evidence exists for a more complex morphology. The aim of this study was to investigate the segmental anatomy of the vastus lateralis muscle and the feasibility of selective flap harvest. Methods: Ten cadaveric lower limbs were investigated. Muscular partitions were identified according to morphologic architecture, vascular supply, and nerve supply; guidelines for selective flap harvest were described. Twenty-three segmental vastus lateralis (n = 14) or chimeric anterolateral thigh–vastus lateralis flaps (n = 9) were raised based on neurovascular segmental supply, and used as noninnervated free flaps for reconstruction of moderate and large defects of the head and neck, trunk, or lower limbs. Intraoperative electrostimulation was used to confirm segmental innervation. Lower limb function was evaluated through the Lower Extremity Functional Scale. Results: The authors clearly identified three anatomical partitions, which receive a constant segmental neurovascular supply, and two aponeuroses. The authors successfully applied the proposed guidelines for flap harvesting to all 23 patients. Intraoperative electrostimulation confirmed functional integrity of both the flap and the spared partitions. All muscle flaps survived. Donor-site morbidity was negligible, with comparable mean preoperative and postoperative Lower Extremity Functional Scale values (67.7 versus 67.4; p > 0.05). Conclusions: This study provides detailed knowledge on the morphologic and neurovascular anatomy of the vastus lateralis muscle, which supports the authors’ guidelines for selective flap harvesting. The technique described is safe and minimizes surgical damage.
1 May 2014 in Journal of Oral and Maxillofacial Surgery