Suzana Cantanhede Orsini Machado de Sousa

Homeobox genes: a molecular link between development and cancer

Homeobox genes are regulatory genes encoding nuclear proteins that act as transcription factors, regulating aspects of morphogenesis and cell differentiation during normal embryonic development of several animals. Vertebrate homeobox genes can be divided in two subfamilies: clustered, or HOX genes, and nonclustered, or divergent, homeobox genes. During the last decades, several homeobox genes, clustered and nonclustered ones, were identified in normal tissue, in malignant cells, and in different diseases and metabolic alterations. Homeobox genes are involved in the normal teeth development and in familial teeth agenesis. Normal development and cancer have a great deal in common, as both processes involve shifts between cell proliferation and differentiation. The literature is accumulating evidences that homeobox genes play an important role in oncogenesis. Many cancers exhibit expression of or alteration in homeobox genes. Those include leukemias, colon, skin, prostate, breast and ovarian cancers, among others. This review is aimed at introducing readers to some of the homeobox family functions in normal tissues and especially in cancer.

Myoepithelial cell markers in salivary gland neoplasms.

We compared the immunoexpression of 5 myoepithelial cell (MEC) markers (asmooth-muscle actin, calponin, h-caldesmon, vimentin, and S-100-protein) using 16 pleomorphic adenomas (PA), 15 adenoid cystic carcinomas (ACC), and 3 epithelialmyoepithelial carcinomas (EMC) of salivary glands. The cx-smooth-muscle actin was useful for identification of MECs, especially in cribriform and tubular ACC, followed by EMC. Calponin was similar to ct-smooth-muscle actin, except for polygonal and plasmacytoid cells of PA and for solid ACC, which showed a-smooth-muscle actin negative and calponin positive. H-caldesmon was negative. Vimentin immunostained all MEC types, and was negative in luminal cells. S-100 protein was expressed both in the nuclei and cytoplasm of MECs and luminal cells, especially in PA. The best way to identify MEC is using a-smooth-muscle actin or calponin, plus vimentin, since in tumors MECs are hardly ever fully differentiated.

Photodynamic therapy mediated by methylene blue dye in wound healing.

OBJECTIVE We sought to investigate the wound-healing process after photodynamic therapy (PDT) mediated by methylene blue dye (MB). BACKGROUND DATA Few scientific studies show the PDT roles in wound healing. MATERIALS AND METHODS One hundred rats were given a circular wound on the back, inflicted with a 6-mm-diameter punch. The animals were divided into four groups: control (no treatment); dye (topical application of MB); laser (InGaAlP, 117.85 J/cm(2), 100 mW, 660 nm, single point); and PDT (topical application of MB followed by laser irradiation). After 1, 3, 5, 7, and 14 days, the cutaneous wounds were photographed and assessed with histopathologic examination by using light microscope. Changes seen in edema, necrosis, inflammation, granulation tissue, re-epithelialization, and number of young fibroblasts were semiquantitatively evaluated. The wound-area changes were measured with special software and submitted to statistical analysis. RESULTS The laser group demonstrated the smallest wound area at 14 days after the surgical procedure (p < 0.01). Concerning complete re-epithelialization, the laser group showed it at 5-7 days after surgery, whereas the PDT and the other groups showed it at 14 days. CONCLUSIONS Laser interaction with tissue is somehow changed when exposed to the MB. PDT mediated by MB was not prejudicial to wound healing, as no delay occurred compared with the control group.

Altered cytokeratin expression in actinic cheilitis

Background:  Actinic cheilitis (AC) is a widely recognized precancerous lesion of the lip. Varying degrees of epithelial dysplasia may be present. However, no studies have correlated epithelial changes with cytokeratin expression that might reflect the disordered maturation that is probably occurring.

Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplification

INTRODUCTION It is still controversial whether human papillomavirus (HPV) can be considered a risk factor in oral carcinogenesis. The aim of this study was to detect HPV DNA in 50 cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas, using in situ hybridization with signal amplification (CSA-ISH). METHODS HPV DNA was assessed in paraffin sections using CSA-ISH with a wide-spectrum biotinylated DNA probe. In HPV-positive cases, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed. RESULTS The overall prevalence of HPV infection was 24%, markedly higher than that found in the control group. Results showed a discrete proportional relationship in the indices found in leukoplakia with no dysplasia, leukoplakia with dysplasia, and squamous cell carcinoma, but this was not statistically significant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. In genotyping, HPV types 16/18 were the most prevalent, and types 6/11 were only found in groups of mild or no dysplasia. CONCLUSION The results suggest that HPV is not likely to play a role in the progression of malignant transformation in oral lesions. Nevertheless, the increased prevalence of HPV infection compared to normal oral mucosa and the fact that high-risk HPV types were the most frequently identified do not allow the exclusion of HPV as a risk factor in oral carcinogenesis.

Comparative immunoprofile of polymorphous low-grade adenocarcinoma and canalicular adenoma

Immunohistochemistry is an important tool when dealing with salivary gland neoplasms. Canalicular adenoma and polymorphous low-grade adenocarcinoma may share some histologic characteristics that can cause difficulties in their separation. In the present study, cases of polymorphous low-grade adenocarcinoma and canalicular adenoma were submitted to a panel of antibodies to evaluate the differences in their immunoprofiles. The results obtained showed that, while vimentin is only expressed by polymorphous low-grade adenocarcinoma, CK7 and CK8 are present in both neoplasms. Therefore, vimentin is the best marker to differentiate between these tumors.

Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Head and neck cancer patients receiving LLLT for oral mucositis, for example, might have remaining tumor cells that could be stimulated by LLLT. This study demonstrated that LLLT (GaAlAs--660 nm or 780 nm, 40 mW, 2.05, 3.07 or 6.15 J/cm²) can modify oral dysplastic cells (DOK) and oral cancer cells (SCC9 and SCC25) growth by modulating the Akt/mTOR/CyclinD1 signaling pathway; LLLT significantly modified the expression of proteins related to progression and invasion in all the cell lines, and could aggravate oral cancer cellular behavior, increasing the expression of pAkt, pS6 and Cyclin D1 proteins and producing an aggressive Hsp90 isoform. Apoptosis was detected for SCC25 and was related to pAkt levels.

Glandular odontogenic cyst: report of a case with cytokeratin expression.

The glandular odontogenic cyst is a rare lesion that was recognized as a distinct entity in the latest WHO typing of odontogenic tumors. We report a glandular odontogenic cyst that recurred after surgical removal from the anterior mandible of a 54-year-old white man. Immunohistochemical study showed that the cystic epithelium reacted positively to antibodies directed against cytokeratins (CKs) 7, 13, 14, and 19 and negatively to CKs 8 and 18.

Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene Derivatives

UNLABELLED Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C₇₀ and novel C₈₄O₂ fullerenes were functionalized with and without an additional deca-tertiary ethyleneamino-chain as an electron source, giving rise to two distinct pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18 and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was better at longer wavelengths; the ratio between killing obtained with LC-19 and LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength. The incorporation of a deca-tertiary amine chain in the C₈₄O₂ fullerene gave more PDT killing when excited with shorter wavelengths or in the presence of low ascorbate concentration through higher generation of hydroxyl radicals. Photoactivated C₈₄O₂ fullerenes induced apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage demonstrated by acridine orange and rhodamine 123 fluorescent probes. FROM THE CLINICAL EDITOR Photoactivated C₇₀ and C₈₄O₂ fullerenes were demonstrated to induce apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage, as a function of wavelength. The study is paving the way to future clinical uses of these agents in photodynamic therapy.

Central odontogenic granular cell tumor: immunohistochemical study of two cases.

Abstract Central odontogenic granular cell tumor (COGCT) is a very uncommon tumor, with only 21 reported cases in the literature. In this study, we attempted to determine immunohistochemical aspects of the tumor that might light on its histogenesis. Two cases occurring in the maxilla of young patients (19 and 25 years old) were studied. The epithelial tumor cells were positive only for cytokeratins 13 and 14 while the granular cells were positive for vimentin and also for CD68. Cells positive to S-100 protein were seen adjacent to and within the epithelial islands. Those results support the theory that the granular cells of COGCT are of mesenchymal origin and, probably, modified fibroblasts.