RESUMO
PURPOSE: Occult metastasis is a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). Sentinel lymph node (SLN) biopsy (SLNB) is a promising method to detect such metastases. The present study aimed to evaluate the diagnostic reliability of SLNB with computed tomography lymphography (CTL) for early-stage OSCC and to clarify patient outcomes after SLNB. METHODS: The medical records of 42 patients with T1 or T2 cN0 OSCC who had undergone CTL the day before surgery were retrospectively collected and statistically analyzed. RESULTS: SLNs were identified on CTL in 41 of 42 OSCC patients (97.6 %). Micrometastases were detected in 10 of 41 cases (24.4 %) and 11 of 65 SLNs (16.9 %) by intraoperative pathological diagnosis. Three cases showed occult metastasis within a year after the primary operation. Specificity and negative predictive value were 76.9 % and 90.3 %, respectively. The cumulative 5-year regional recurrence-free rate was 89.7 % in 31 SLNB-negative patients. Five-year overall and disease-free survival rates were 86.9 % and 70.1 %, respectively, in the 41 cases with identified SLNs. CONCLUSION: CTL offers acceptable results and appears likely to be effective in treating early-stage OSCC patients with low-invasive surgery. Further investigation is necessary to compare radioisotope-based methods.
RESUMO
Vascular endothelial growth factor (VEGF) serves an important role in new blood vessel formation or angiogenesis, which is a critical event in tumor growth and metastasis. Bevacizumab is a humanized monoclonal antibody against VEGF-A, whereas S-1 is a fluoropyrimidine antineoplastic agent that induces apoptosis in various types of cancer cells. The present study evaluated the antitumor effects of bevacizumab in combination with 5-fluorouracil (5-FU) or S-1 against oral squamous cell carcinoma (OSCC) in vitro and in vivo. Two human OSCC cell lines were used, namely the high VEGF-A-expressing HSC-2 cells and the low VEGF-A-expressing SAS cells. MTT assay was used to evaluate the effect of bevacizumab and/or 5-FU against HSC-2 and SAS cell proliferation. Additionally, the antitumor effect of bevacizumab was evaluated alone and in combination with S-1 against HSC-2 tumors in nude mice. S-1 (6.9 mg/kg/day) was administered orally every day for 3 weeks, and bevacizumab (5 ml/kg/day) was injected intraperitoneally twice per week for 3 weeks. Apoptotic cells in mouse tumors were detected using the TUNEL method, and cell proliferation and microvessel density (MVD) were determined by immunohistochemical staining of Ki-67 and CD31, respectively. Bevacizumab alone did not inhibit OSCC cell proliferation in vitro, and did not exhibit any synergistic inhibitory effect in combination with 5-FU in vitro. However, combined bevacizumab and S-1 therapy exerted synergistic and significant antitumor effects in vivo on HSC-2 tumor xenografts, and induced apoptosis in tumor cells. Furthermore, this combination therapy led to decreased MVD and cell proliferative abilities, as well as increased apoptosis in residual tumors. The present findings suggested that the bevacizumab plus S-1 combination therapy may exert antitumor effects in high VEGF-A-expressing OSCC cells.
RESUMO
Carbonyl reductase 1 (CBR1) is an enzyme that catalyzes the reduction of numerous compounds by using NADPH-dependent oxidoreductase activity. Decreased expression of CBR1 is associated with disease progression and an unfavorable outcome in several types of malignancies. The purpose of the current study was to determine whether CBR1 expression could be a useful prognostic factor in patients with oral squamous cell carcinoma (OSCC). Therefore, its mechanisms of action were investigated in order to understand how CBR1 affects cancer cell behavior in vitro. CBR1 expression was evaluated using immunohistochemistry and tissue samples obtained from 90 patients with OSCC. The associations between CBR1 expression, clinicopathological characteristics and patient survival were also analyzed. In addition, the role of CBR1 in cancer cell invasion and metastasis was examined, along with its underlying molecular mechanisms, via transfecting CBR1-siRNA into the HSC2 human OSCC cell line. Immunohistochemical analysis revealed that biopsy tissue samples of 71.1% of the patients with OSCC were positive for CBR1. In addition, CBR1 expression status was correlated with the N classification (P<0.0001), stage (P=0.0018) and outcome (P=0.0095). Furthermore, a statistical correlation was determined between the protein expression status and overall survival (P=0.0171). In vitro studies indicated that the suppression of CBR1 by CBR1-siRNA increased cancer cell proliferative, wound healing and migratory abilities. These findings suggest that low expression levels of CBR1 may affect cancer prognosis, and that CBR1 may have potential as a prognostic factor for patients with OSCC.
RESUMO
BACKGROUND: Programmed death-1 ligand-1 (PD-L1) an important cancer biomarker that can suppress the immune system and its high expression is often reported to be related with increased tumor aggressiveness in some cancers. Here, we examined and evaluated PD-L1 expression in patients with malignant salivary gland tumor. Moreover, the relationship between PD-L1 immunolocalization and clinical pathological features, as well as the prognosis of malignant salivary gland tumors was investigated. METHODS: We examined PD-L1expression in 47 patients with malignant salivary gland tumor by immunohistochemical staining. PD-L1 positivity was defined as ≥5% in tumor cell membrane and evaluated according to three categories (0% = 0, < 5% = 1, ≥5% = 2) in tumor-infiltrating mononuclear cells (TIMCs). Fisher's exact test was used to compare between PD-L1 expression and clinico-pathological features, and Kaplan-Meier method was used to estimate the distribution of OS by PD-L1 positivity. RESULTS: PD-L1 expression was detected in 51.1% of malignant salivary gland tumor tissues. No association was observed between PD-L1 immunolocalization in tumor and patient gender, or age. However, PD-L1 immunodetection of tumor cell membranes was significantly associated to stage, recurrence or metastasis after surgery, and patient outcome. On the other hand, PD-L1 immunodetection of tumor-infiltrating mononuclear cells (TIMCs) was significantly associated to recurrence or metastasis after surgery, and patient outcome. PD-L1 positivity in both tumor cell membrane and TIMCs was associated with shorter overall survival (OS) (p = 0.002 and p = 0.016, respectively). CONCLUSION: These findings suggested that patients with PD-L1 positive tumors or TIMCs appear to have poor clinical outcomes in malignant salivary gland tumors.
Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares/patologia , Adulto JovemRESUMO
Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.
Assuntos
Dermatite/tratamento farmacológico , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fluoruracila/efeitos adversos , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Animais , Feminino , Alimentos Formulados , Glutamina/metabolismo , Japão , Masculino , Mesocricetus , Camundongos , Camundongos Nus , Pele/efeitos dos fármacos , Pele/metabolismo , Estomatite/metabolismoRESUMO
BACKGROUND/AIM: To evaluate the efficacy of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) in oral cancer patients. PATIENTS AND METHODS: Oral cancer patients receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy were administered. On day 1, 0.75 mg palonosetron was intravenously administrated just before chemotherapy. RESULTS: The primary endpoint was the proportion of patients with a complete response (CR) and the secondary endpoint was the proportion of patients with complete control (CC) during the acute and delayed phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87 courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR and 70 of 87 courses (80.5%) had CC. CONCLUSION: Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.
Assuntos
Antineoplásicos/uso terapêutico , Isoquinolinas/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Vômito/prevenção & controle , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Isoquinolinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Palonossetrom , Quinuclidinas/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/uso terapêutico , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
Gimeracil or 5-chloro-2,4-dihydroxypyridine (CDHP) enhances the antitumor effects of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU. CDHP, as part of a combination therapy, was also reported to exert a radiosensitizing effect. Therefore, CDHP may have underlying mechanisms of action other than DPD inhibition. The focus of the present study was to investigate the antitumor effects of CDHP and cisplatin (CDDP) combination treatment in vitro and in vivo against oral squamous cell carcinoma (OSCC) tumors. The inhibitory growth effects of CDHP and/or CDDP treatment on SAS and HSC2 cells were examined using an MTT assay. The expression levels of DNA double strand break repair proteins, including Ku70, DNA-dependent-protein kinase catalytic subunit (DNA-PKcs), Rad50 and Rad51 in CDHP and/or CDDP-treated cells were detected using western blotting. Nude mice with SAS or HSC2 tumors were treated with CDHP (administered orally 7 times/week) and/or CDDP (administered by intraperitoneal injection once/week) for 2 weeks. Combined treatment of CDHP and CDDP significantly suppressed the growth of SAS and HSC2 cells in vitro and that of tumors in vivo compared with the effects caused by single drug only or control treatments. Western blotting demonstrated that the expression levels of Ku70, DNA-PKcs, Rad50 and Rad51 were downregulated in cells treated with CDHP and CDDP combination treatment. Immunohistochemistry also identified that the expression of DNA double strand break repair proteins was downregulated in tumors treated with CDHP and CDDP combination treatment compared with that of tumors treated with CDDP alone or control. The results of the current study suggest that CDHP may be responsible for enhancing the antitumor effects of CDDP by suppressing the DNA double strand break repair system. Therefore, the combination of CDHP and CDDP may be a potential effective option for OSCC treatment.
RESUMO
Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.
RESUMO
We focused on the expression of Calreticulin (CALR) in oral squamous cell carcinoma (OSCC) on the basis of proteomic differential display analysis data. We used QR-32 cells in this study which is a regressive murine fibrosarcoma cell clone; and QRsP-11, a progressive malignant tumor cell clone originated from QR-32. CALR is an endoplasmic reticulum luminal Ca2+-binding chaperone protein, which is thought to affect the tumor behavior of various malignancies. This study was aimed to determine the usefulness of CALR as a prognostic factor in patients with OSCC. We investigated the expression of CALR in tissue samples taken from 111 OSCC patients by immunohistochemistry, and we also analyzed the relationship between CALR expression and patients' clinicopathological characteristics as well as patient survival. Positive immunohistchemical staining of CALR was observed in the cancer cell cytoplasm. Among 111 patients, high expression of CALR was observed in 44 patients (39.6%), whereas low expression was observed in 67 patients (60.4%). Significant association was found between CALR expression and T classification (P=0.0027), N classification (P=0.0219), stage (P=0.0013), and patient outcome (P=0.0014). Log-rank test showed that, there is a significant difference (P<0.0001) in 5-year survival rates between patients showing CALR high-expression (59.1%) and CALR low-expression (86.6%). According to our Multivariate analysis, reduced term survival of patients was correlated to high levels of CALR expression (P<0.0001). Our findings suggest that elevated expression of CALR might play an important role in tumor progression in OSCC, and could be considered as a useful prognostic factor in OSCC patients.
RESUMO
Stathmin 1 is an oncoprotein that regulates cell cycle by modulating microtubule dynamics and can cause uncontrolled cell proliferation in mutated state. The present study examined stathmin 1 expression in 49 patients with oral squamous cell carcinoma (OSCC) treated with docetaxel (Doc)-containing regimens by immunohistochemical staining. Moreover, we investigated the relationship between stathmin 1 expression and clinicopathological features, as well as the prognosis of above patients. Stathmin 1 could be detected in the cytoplasm of tumor cells in OSCC tissues though its expression level was variable. There was no correlation between stathmin 1 expression and patient gender, or age in OSCC. However, stathmin 1 expression of tumor cell was significantly correlated with T classification (P = 0.0017), N classification (P = 0.0171), stage (P < 0.0001), therapeutic efficacy (P < 0.0001), and patient outcome (P = 0.0387). In addition, high expression of stathmin 1 in tumor cells was associated with shorter overall survival (OS, P = 0.0017). Multivariate analysis also revealed that high expression of stathmin 1 was a predictor of reduced survival (P = 0.0241). These findings suggest that patients with OSCC tumors showing high expression of stathmin 1 might have poor therapeutic effects and worse clinical outcomes in OSCC treated with Doc-containing regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Bucais/diagnóstico , Estatmina/genética , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Docetaxel , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Estatmina/metabolismo , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Gimeracil or 5-chloro-2, 4-dihydroxypyridine (CDHP) has been reported to exert radiosensitization effects in cancer cells by suppressing DNA repair pathways. Here, we investigated the antitumor effect of gimeracil and radiation combination therapy against oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: The antitumor activity of gimeracil and/or radiation was investigated in HSC2 and/or SAS cells by growth inhibition assays and clonogenic survival assay. The expression of DNA double-strand break repair proteins were assessed by western blotting and immunohistochemistry, also fluorescent measurements of intracellular reactive oxygen/nitrogen species (ROS/RNS) were carried out in gimeracil and/or radiation-treated HSC2 cells/tumors. RESULTS: Gimeracil and radiation combination treatment significantly inhibited OSCC cell/tumor growth and colony formation. Down-regulated expressions of DNA double-strand break repair proteins were observed in gimeracil and/or radiation treated cells/tumors. Additionally, the growth inhibitory effect of this combination treatment was associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation. CONCLUSION: Gimeracil might exert radiosensitizing effects on OSCC cells.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Bucais/patologia , Piridinas/farmacologia , Radiossensibilizantes/farmacologia , Animais , Humanos , Técnicas In Vitro , Camundongos , Camundongos NusRESUMO
The purpose of this study was to clarify characteristics of posed smiles for Class III female patients before and after orthognathic surgery. Just before retrusion surgery and the removal of fixation plates, 2 sets of posed smiles were recorded for 7 Class III female patients. As normal controls, 7 healthy female volunteers were also recorded. Using our video-based motion analyzing system, range images and 5â×â5 virtual grids projected onto the lips were recorded for all patients while making a posed smile. The gravity for each area in the lips was calculated from the intersections of the virtual grids. Principal component analysis was applied to the normalized virtual grids, that is, a homologous model of lip shape, for all frames of the posed smiles. While the sample size was too small to generalize from these results, we found that the upper vermilion shifted posteriorly and laterally in posed smiles for Class III female patients after retrusion surgery as compared with the preoperative posed smiles. In addition, the characteristic lip movements during postoperative posed smiles for Class III female patients did not resemble those of the normal controls.
Assuntos
Expressão Facial , Osteotomia/métodos , Análise de Componente Principal/métodos , Sorriso/fisiologia , Adolescente , Adulto , Feminino , Humanos , Lábio/fisiologia , Adulto JovemRESUMO
BACKGROUND: The cancer stem cells (CSCs), a small subpopulation of cells in tumor are responsible for the tumor initiation, growth, recurrence and metastasis of cancer, as well as resistance of cancers to drugs or radiotherapy. CSCs are an important target for the development of novel strategies in cancer treatment. However, CSCs-targeted new anti-cancer drug discovery is currently hindered by the lack of easy and reliable methods for isolating, collecting and maintaining sufficient number of CSCs. Here, we examined whether introduction of defined reprogramming factors (Oct4, shp53, Sox2, Klf4, l-Myc and Lin28) into HSC2 tongue cancer cells could transform the HSC2 into HSC2 with CSCs properties. METHODS: We introduced the defined reprogramming factors into HSC2 tongue cancer cells via episomal vectors by electroporation method to generate transfectant cells. We investigated the malignant properties of the transfectant cells by cell proliferation assay, migration assay, wound healing assay, sphere formation assay, chemosensitivity and radiosensitivity assay in vitro; and also examined the tumorigenic potential of the transfectants in vivo. RESULTS: The transfectant cells (HSC2/hOCT3/4-shp53-F, HSC2/hSK, HSC2/hUL, HSC2/hOCT3/4-shp53-F + hSK, HSC2/hOCT3/4-shp53-F + hUL, HSC2/hSK + hUL, HSC2/hOCT3/4-shp53-F + hSK + hUL) displayed a malignant phenotype in culture and form tumors on the back of nude mice more efficiently than parental HSC2 and control HSC2/EGFP transfectant cells. They exhibited increased resistance to chemotherapeutic agents; 5-fluorouracil, cisplatin, docetaxel, trifluorothymidine, zoledronic acid, cetuximab, bortezomib and radiation when compared with HSC2 and HSC2/EGFP. Among all the transfected cells, HSC2/hOCT3/4-shp53-F + hSK + hUL cell containing all of the reprogramming factors showed the most aggressive and malignant properties and presented the highest number of spheres in the culture medium containing human recombinant fibroblast Growth Factor-2 (FGF-2) and epidermal Growth Factor (EGF). CONCLUSION: These findings suggest that artificial cancer stem cells obtained by the induction of cellular reprogramming may be useful for investigating the acquisition of potential malignancy as well as screening the CSCs-targeting drugs.
Assuntos
Reprogramação Celular , Células-Tronco Neoplásicas/patologia , Neoplasias da Língua/patologia , Transfecção/métodos , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Eletroporação , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Fator 4 Semelhante a Kruppel , Células-Tronco Neoplásicas/metabolismo , Esferoides Celulares/metabolismo , Neoplasias da Língua/metabolismo , Células Tumorais CultivadasRESUMO
Cancer cells show enhanced glucose consumption and lactate production even in the presence of abundant oxygen, a phenomenon known as the Warburg effect, which is related to tumor proliferation, progression and drug-resistance in cancers. Hypoxia-inducible factor-1 (HIF-1) and several members of Phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway positively contribute to the Warburg effect, whereas AMP activated protein Kinase (AMPK) acts as a negative regulator. Targeting the regulator molecules of Warburg effect might be a useful strategy to effectively kill cancer cells. Metformin was reported to be effective against various cancers as it inhibits cell proliferation by activating AMPK, and inhibiting mTOR and HIF-1α. Several studies suggested the efficacy of metformin with 5-fluorouracil (5-FU) against esophageal and colon cancer. In this study, we evaluated the efficacy of metformin and 5-FU combined therapy against human oral squamous cell carcinoma (OSCC) in vitro and in vivo. MTT assay and TUNEL assay revealed that metformin (4 mg/ml) and 5-FU (2.5 µg/ml) combination treatment effectively inhibited cell growth and induced apoptosis in OSCC cell lines (HSC2, HSC3 and HSC4) compared to either agent alone. Lactate colorimetric assay detected decreased level of lactate in the supernatants of metformin and 5-FU treated cells compared to cells treated with metformin or 5-FU. Western blot analysis showed marked downregulation of HIF-1α and mTOR expression, and upregulation of AMPKα in cells treated with metformin and 5-FU combination treatment. Combination therapy with metformin (200 mg/kg, i.p.) and 5-FU (10 mg/kg, i.p.) for 4 weeks (5 days/week) effectively reduced HSC2 tumor growth (77.6%) compared to metformin (59.9%) or 5-FU (52%) alone in nude mice. These findings suggest that metformin and 5-FU combined therapy could exert strong antitumor effect against OSCC through the inhibition of Warburg phenomenon in tumor cells.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/administração & dosagem , Metformina/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/biossíntese , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Camundongos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/biossíntese , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Therapeutic cancer vaccines are designed to treat cancer by boosting the endogenous immune system to fight against the cancer. In the development of clinically effective cancer vaccines, one of the most practical objectives is to identify adjuvants that are capable of optimizing the vaccine effects. In this study, we explored the potential of polyinosinic-polycytidylic acid (poly(I:C)) and LAG-3-Ig (soluble recombinant protein of lymphocyte activation gene-3 [LAG-3] extracellular domain fused with human IgG Fc region) as adjuvants for P1A tumor antigen peptide vaccine in a pre-established P815 mouse tumor model with a transfer of tumor-specific T cells. Whereas the use of poly(I:C) or LAG-3-Ig as a signal adjuvant induced a slight enhancement of P1A vaccine effects compared to incomplete Freund's adjuvant, combined treatment with poly(I:C) plus LAG-3-Ig remarkably potentiated antitumor effects, leading to complete rejection of pre-established tumor and long-term survival of mice. The potent adjuvant effects of poly(I:C) plus LAG-3-Ig were associated with an enhanced infiltration of T cells in the tumor tissues, and an increased proliferation and Th1-type cytokine production of tumor-reactive T cells. Importantly, the combined adjuvant of poly(I:C) plus LAG-3-Ig downregulated expressions of PD-1, LAG-3, and TIGIT on P1A-specific T cells, indicating prevention of T cell exhaustion. Taken together, the results of the current study show that the combined adjuvants of poly(I:C) plus LAG-3-Ig with tumor peptide vaccine induce profound antitumor effects by activating tumor-specific T cells.
Assuntos
Antígenos CD/imunologia , Vacinas Anticâncer/imunologia , Imunoglobulina G/imunologia , Poli I-C/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos CD/administração & dosagem , Antígenos CD/genética , Linfócitos T CD8-Positivos/efeitos dos fármacos , Humanos , Imunoglobulina G/administração & dosagem , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/imunologia , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
Two cases where aberrant tissue was attached to the lower lip mimicking the inferior labial frenum were reported. The frenum-like tissue extended from the gingival margin between the lower left deciduous central and lateral incisors in case 1 and between the lower right deciduous central and lateral incisors in case 2, to the dry lower lip. Histologically, the resected specimen was regarded as normal oral mucosa covered with stratified squamous epithelium, without a clear amniotic band. The frenum-like tissue of the lower lip found in both our patients was diagnosed as a category of oral synechiae, of unknown origin.
Assuntos
Coristoma/diagnóstico , Freio Labial , Doenças Labiais/diagnóstico , Mucosa Bucal , Criança , Pré-Escolar , Coristoma/patologia , Coristoma/cirurgia , Feminino , Humanos , Freio Labial/patologia , Freio Labial/cirurgia , Doenças Labiais/patologia , Doenças Labiais/cirurgia , MasculinoRESUMO
PURPOSE: Oral mucositis induced by radiation or chemoradiation can compromise the quality of life of oral squamous cell carcinoma (OSCC) patients. The present study was designed to evaluate the preventive effects of elemental diet (ED), Elental®, on radiotherapy- or chemoradiotherapy-induced mucositis in OSCC patients. PATIENTS AND METHODS: Seventy-four patients who underwent radiation (60-70 Gy) with/without chemotherapy [S-1, cisplatin (CDDP), CDDP plus S-1] were enrolled in this retrospective study; 37 had received Elental® during treatment (Elental® group) and 37 had not (control group). Factors related to alleviation of oral mucositis were identified by multivariate logistic regression analysis. Rates of completion of chemoradiation treatments were compared between Elental® and control groups according to the treatment regimen. The comparison of the nutritional status between groups was also performed. RESULTS: Multivariate analysis indicated that the administration of Elental® and no combined chemotherapy (radiation alone) were significant factors associated with the degree of oral mucositis, i.e., most of the patients who consumed Elental® suffered from a lower degree of mucositis compared to the control group. Elental® was associated with a significantly improved rate of completion of chemoradiation (no interruption). There was no significant difference between Elental® group and control group in terms of mean change of body weight or total protein and albumin levels in blood serum before and after (chemo)radiation. CONCLUSIONS: The present study indicates that Elental® is effective for ameliorating oral mucositis induced by (chemo)radiation in OSCC patients. Elental® was also associated with improved completion rates of (chemo)radiotherapy.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/efeitos adversos , Alimentos Formulados , Neoplasias Bucais/radioterapia , Mucosite/dietoterapia , Estomatite/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Qualidade de Vida , Estudos Retrospectivos , Estomatite/induzido quimicamente , Estomatite/dietoterapiaRESUMO
OBJECTIVE: We developed a novel method of producing accurate range images of the velopharynx using a three-dimensional (3D) endoscope to obtain detailed measurements of velopharyngeal movements. The purpose of the present study was to determine the relationship between the distance from the endoscope to an object, elucidate the measurement accuracy along the temporal axes, and determine the degree of blurring when using a jig to fix the endoscope. METHODS: An endoscopic measuring system was developed in which a pattern projection system was incorporated into a commercially available 3D endoscope. After correcting the distortion of the camera images, range images were produced using pattern projection to achieve stereo matching. Graph paper was used to measure the appropriate distance from the camera to an object, the mesial buccal cusp of the right maxillary first molar was measured to clarify the range image stability, and an electric actuator was used to evaluate the measurement accuracy along the temporal axes. RESULTS: The measurement error was substantial when the distance from the camera to the subject was >6.5 cm. The standard error of the 3D coordinate value produced from 30 frames was within 0.1 mm (range, 0.01-0.08 mm). The measurement error of the temporal axes was 9.16% in the horizontal direction and 9.27% in the vertical direction. CONCLUSION: The optimal distance from the camera to an object is <6.5 cm. The present endoscopic measuring system can provide stable range images of the velopharynx when using an appropriate fixation method and enables quantitative analysis of velopharyngeal movements.
Assuntos
Algoritmos , Anormalidades Craniofaciais/cirurgia , Endoscópios , Imageamento Tridimensional/métodos , Movimento , Imagens de Fantasmas , Faringe/fisiopatologia , Anormalidades Craniofaciais/fisiopatologia , Desenho de Equipamento , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND/AIM: Sarcoma of the oral cavity is rare accounting for around 1% of all malignant oral tumors. The purpose of this study was to find important prognostic factors for patients with oral sarcoma. PATIENTS AND METHODS: The study included 1,643 patients examined from April 1980 to March 2010 at the Departments of oral and maxillofacial surgery at multi-institutions who had a histopathological diagnosis of malignant oral tumors. RESULTS: Sarcoma accounted for 19 of 1,643 cases (1.16%) in malignant oral tumors. Histologically, osteosarcoma was most common in 6 of the 19 patients, followed by 3 cases each of leiomyosarcoma and malignant fibrous histiocytoma, 2 of rhabdomyosarcoma and 1 each of angiosarcoma, Ewing's sarcoma, malignant schwannoma, malignant rhabdoid tumor and undifferentiated sarcoma. Irrespective of the histological type, tumor diameter on initial examination was >50 mm in 8 patients, 7 of whom died. Tumor diameter was <50 mm in 11 patients, 6 of whom survived. Distant metastasis was present in 11 patients, 10 of whom died. The local control rate was 42.1% and 5-year survival rate was 36.8%. CONCLUSION: Treatment of patients with tumors over 50-mm long in diameter and distant metastasis is extremely difficult. The incidence of oral sarcoma is very low. However, tumor diameter and presence of distant metastasis are important prognostic factors for oral sarcoma according to this multi-institutional study.
Assuntos
Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Sarcoma/mortalidade , Sarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Prognóstico , Sarcoma/tratamento farmacológico , Análise de SobrevidaRESUMO
Squamous cell carcinoma throughout the epithelium of a lateral cervical cyst is considered extremely rare. This report describes an additional case of this very rare clinical condition. A 70-year-old man presented with a well-defined, immobile, painless mass in the left neck that was excised with a diagnosis of branchial cyst. Histologic findings of the excised specimen were lateral branchial cyst with high-grade dysplasia and carcinoma of the squamous epithelial lining. The patient was followed for more than 2 years 10 months and no evidence of recurrence or other cancer has been found.