RESUMEN
Despite of considerable advances in the diagnostic and therapeutic possibilities, the prognosis of epithelial tumors in the oral cavity is still very poor. A knowledge of the prognostic factors at the beginning of treatment is therefore indispensable for determination of the appropriate therapy for the given patient. These factors may be linked to the patient (e.g. age, sex, general condition and immunological parameters) or to the tumor localization. A survey of the literature reveals that the TNM stage, the grade, the mode of invasion and the depth of the tumor infiltration are generally the most important factors influencing the fate of the patient. The prognosis depends primarily on the clinicopathological parameters, though even if they are known, it is not possible to screen out those patients who are at particular risk of a relapse. During the past 10 years, study of the DNA content distribution, the proliferation markers and certain oncogenes has come into the focus of attention; great interest is also shown in the extracellular matrix components and the metalloproteinases, which play key roles in the invasion and metastasis formation.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Carcinoma de Células Escamosas/genética , Membrana Celular/química , Genes Supresores de Tumor , Humanos , Inmunohistoquímica , Masculino , Neoplasias de la Boca/genética , Oncogenes , Pronóstico , SobrevidaRESUMEN
OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Interleucinas/administración & dosificación , Neoplasias de la Boca/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Complejo CD3/análisis , Carcinoma de Células Escamosas/patología , Ciclofosfamida/administración & dosificación , Células Dendríticas/patología , Femenino , Humanos , Indometacina/administración & dosificación , Inyecciones , Inyecciones Intradérmicas , Antígeno Ki-67/análisis , Células Asesinas Naturales/patología , Leucocitos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Necrosis , Receptores de Interleucina-2/análisis , Linfocitos T/inmunología , Sulfato de Zinc/administración & dosificaciónRESUMEN
Animal experiments were carried out with osteoconductive bone substitute beta-tricalcium phosphate (beta-TCP), with the aim of assessing the effects of the growth factors synthesised by thrombocytes on the speed of beta-TCP incorporation and on the quality of newly formed bone. The question to be answered was the extent to which platelet-rich plasma (PRP) accelerated the resorption of beta-TCP and the formation of new bone. Two teeth were removed symmetrically from each side of the mandible of 12 Beagle dogs; the resulting cavities were filled on one side with beta-TCP alone, and on the other side with a mixture of beta-TCP + PRP (obtained from autologous blood). The quality of the newly formed bone and the effects of this PRP were studied by histological and histomorphometric methods. In week 6, bone formation was already more effective when PRP was applied in comparison with beta-TCP alone, and in week 12 the growth was significantly greater. The results demonstrate that the use of PRP accelerates the remodelling of new bone created by beta-TCP.
Asunto(s)
Plaquetas , Sustitutos de Huesos/farmacología , Fosfatos de Calcio/farmacología , Oseointegración/efectos de los fármacos , Animales , Implantación Dental Endoósea/veterinaria , Perros , Mandíbula/cirugía , Oseointegración/fisiologíaRESUMEN
In 8 cases of maxillary and mandibular osteomyelitis which had failed to respond to traditional surgical and medicinal methods of treatment, a significant improvement could be achieved (in 7 of the 8 cases) by applying an intra-arterial clindamycin therapy. Treatment was carried out similar to the intra-arterial cytostatic perfusion treatment of tumors in the head and neck areas. Clindamycin was administered in daily dosages of 900 mg over a period of 8-23 days.