Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells.

INTRODUCTION: Cisplatin is used as a standard chemotherapeutic agent for head and neck cancer treatment. However, some head and neck cancers have cisplatin resistance, leading to difficulty in treatment and poor prognosis. Overcoming cisplatin resistance remains an important strategy to improve prognoses for head and neck cancer patients. OBJECTIVE: Elucidation of the mechanisms underlying cisplatin resistance can suggest novel targets to enhance the anticancer effects of cisplatin for treating head and neck cancers. MATERIAL AND METHODS: We used a cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR cells using PCR array. Among the genes with expression increased by cisplatin, we specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be induced by chemotherapeutic agents such as cisplatin, radiation, and hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation were analysed using specific RNAi. RESULTS: Results show that SESN1 was induced by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced apoptosis and reduced cell viability through enhancement of ROS after cisplatin treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of hyperthermia with increased ROS, but did not affect the cell-killing effects of radiation. CONCLUSIONS: This study demonstrated the participation of SESN1 in cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a novel molecular target to overcome cisplatin resistance and hyperthermia resistance and improve head and neck cancer treatment.

Clinicopathological Study of Primary Intraosseous Squamous Cell Carcinoma of the Jaw and a Review of the Literature.

PURPOSE: Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant odontogenic tumor that originates from odontogenic epithelial remnants. It is often difficult to diagnose PIOSCC definitively; hence, extraction or surgical treatment is performed before the initial diagnosis in most cases. The present study examined new insights into and prognostic factors of patients with PIOSCC admitted to the authors' department. MATERIALS AND METHODS: An extensive record review was conducted of patients who underwent radical surgery for PIOSCC from January 2001 through December 2014. RESULTS: Of all cases of OSCC, the frequency of PIOSCC was 1.45%. The 2-year relapse-free survival (RFS) and overall survival (OS) rates were 50.0 and 41.6% in all cases, respectively. Three patients underwent surgery or tooth extraction before the initial diagnosis; in fact, intervention before initial diagnosis was found to be an important poor prognostic factor for RFS and OS. In contrast, patients who were not treated before the initial diagnosis was made did not exhibit any locoregional recurrence. CONCLUSIONS: The treatment of PIOSCC should be similar to that for oral cancer with at least clinical stage T3N0 in the National Comprehensive Cancer Network clinical practice guidelines. In addition, cases of PIOSCC that are not treated before the initial diagnosis are more likely to obtain a good prognosis.

Successful elective surgery in a patient with a positive preoperative cocaine toxicology screen.

A positive result on preoperative cocaine toxicology screening has traditionally been a contraindication to immediate nonemergency surgery. We describe a case of major but not emergency head and neck surgery on a patient with a massive ossifying fibroma whose preoperative toxicology screen was positive for cocaine. The surgery was completed without complication, and the patient recovered uneventfully. The decision to proceed with surgery was based on the fact that the results of urine cocaine screening can remain positive long after the cocaine itself has become metabolically inactive, and thus the results may not reflect the actual presence of cocaine or the degree of current intoxication. Our institution has concluded that elective head and neck surgery may be safely performed in carefully selected, hemodynamically stable patients who have tested positive for cocaine ingestion provided that they have been closely observed for 8 hours preoperatively and that they have provided informed consent. Outcome studies are needed.

[Influence of chemotherapy regimen on antioxidant level in patients with locally-advanced tumors of the maxilla, nasal and paranasal sinuses].

The study dealt with effect of chemoradiotherapy on the oxidant/antioxidant system in 57 patients with locally-advanced tumors (stage III-IV) of the maxilla, nasal and paranasal sinuses. Therapy modalities ranged from systemic chemoradiotherapy (22), intraarterial chemoradiotherapy + UHF-hyperthermia (20) and intraarterial chemotherapy + radiotherapy (15). The most frequent regimen of chemotherapy involved cisplatin 15 mg/ m2, total dose of 100 mg; fluorouracil 600 mg/m2, total dose of 2,000-3,000 mg, and doxorubicin 15 mg/m2, total dose of 40-60 mg. As far as telegammatherapy is concerned, all patients received STD of 3 Gy and TTD of 40-60 Gy. Unlike systemic chemoradiotherapy, continuous intraarterial chemoradiotherapy with UHF-hyperthermia or without it was followed by lower incidence of enhanced oxidative reaction response and tumor-related endotoxicosis.

Adjuvant antiangiogenic therapy for giant cell tumors of the jaws.

PURPOSE: To further evaluate a novel treatment protocol for the management of aggressive giant cell lesions (GCLs) consisting of enucleation followed by adjuvant subcutaneous interferon alpha therapy. PATIENTS AND METHODS: Using a retrospective case series study design, a sample of patients with aggressive GCLs was enrolled between April 1995 and June 2006. Lesions were enucleated with preservation of vital structures. Postoperatively, the patients received daily subcutaneous interferon alpha (3 million units/m2 of body surface area). Interferon treatment continued with regular clinical and radiographic follow-up until the surgical defects filled in with bone, as demonstrated by panoramic radiographs and confirmed by computed tomography. Side effects, such as fever, fatigue, weight loss, decreased white blood cell count, decreased platelet count and elevated liver enzymes, were monitored. After completion of interferon therapy, patients followed for 2 years without evidence of recurrence were considered cured of disease. RESULTS: The study sample was comprised of 26 subjects (65% female) with a mean age of 18.5 years. At the time of this writing, 16 of the subjects have completed the protocol and are cured of disease, 6 are in remission, and 4 are in active treatment. Four subjects experienced significant side effects from the interferon, requiring modification of treatment. CONCLUSIONS: Enucleation of aggressive GCLs with preservation of vital structures and adjuvant interferon is an excellent strategy for managing aggressive GCLs. Approximately 15% of subjects developed significant side effects limiting interferon administration and necessitating alternative therapies.

Ivory osteoma of the craniofacial skeleton.

The authors describe the clinical presentation, investigation, and surgical management of two cases of benign ivory osteoma of the craniofacial skeleton. In the first case, a bony mass located over the frontal region had become a cosmetic burden to the patient, and she requested removal with minimal morbidity. Accordingly, an endoscopic procedure, with minimal access incisions located behind the hairline, was devised. In the second case, the patient, a Jehovah's Witness, presented with a long history of slowly enlarging bony masses over the maxilla and in the pterygopalatine space. She finally requested surgical intervention when the symptoms of pain related to fifth nerve compression at the foramen ovale became intolerable. Key aspects of the preoperative and perioperative management strategies used to avoid blood transfusion are detailed, as is the surgical approach, which included a bicoronal scalp flap with temporary removal of the zygomatic arch and the coronoid process. Finally, the etiology, histology, and natural history of ivory osteomas are discussed.

Granuloma periférico de células gigantes: caso clínico y revisión de la literatura / The peripheral giant cell granuloma: clinical case and review of literature review

El granuloma periférico de células gigantes, es una lesión exofítica que se sitúa en la zona gingival y en el hueso alveolar, de carácter benigno y etiología no muy bien definida. Representa el 7 por ciento de los tumores benignos de los maxilares. En este trabajo, describimos un caso en una mujer de 13 años de edad, con una lesión de crecimiento rápido, localizada en el maxilar superior y realizamos una revisión bibliográfica, estudiando los aspectos epidemiológicos, clinicopatológicos y los posibles tratamientos de este proceso. (AU)

Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case report and differential diagnosis.

We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and markedly pigmented appearance. Histology showed neoplastic growths of atypical epithelial cells that occasionally contained melanin pigments. Melanocytes with dendritic processes were often found in the tumor cell clusters, and solitary or aggregated melanophages were scattered within the dense fibrovascular stroma. The tumor cells were diffusely positive for cytokeratins and epithelial membrane antigen, and focally positive for vimentin, neuron specific enolase, neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural studies showed well-developed intercellular junctions, mainly desmosomes, and glycogen particles. In addition, some tumor cells contained melanosomes and/or a few neurosecretory granules. We consider that the present tumor suggests a close association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.

In vitro effects of hyperthermia combined with cisplatin or peplomycin on the human maxillary carcinoma cell line IMC-2.

We examined the interactive effects of hyperthermia combined with cisplatin (CDDP) (0.5 micrograms/ml) or peplomycin (PEP) (1.0 microgram/ml) on surviving fractions of human maxillary carcinoma IMC-2 cells. Either CDDP or PEP enhanced the 44 degree C thermosensitivity of thermotolerant cells after heating at 42 degrees C for 2 hours. The development of thermotolerance at 42 degrees C with either of the two drugs for 2 hours was not inhibited by CDDP, but it was partially inhibited by PEP. Moreover, for PEP throughout the entire period of 42-44 degrees C step-up heating, the 44 degree C thermosensitivity of thermotolerant cells after heating at 42 degrees C with PEP for 2 hours was enhanced similarly to that at 44 degrees C with PEP. Heating at 42 degrees C combined with either of the two drugs showed a marked interactive effect.

Enhancement of cisplatin sensitivity and platinum uptake by 40 degrees C hyperthermia in resistant cells.

We studied the cytotoxic and pharmacological properties of 40 degrees C hyperthermia and CDDP in CDDP-sensitive (IMC-3) and CDDP-resistant (IMC-3-DDP) human maxillary carcinoma cells. Heating at 40 degrees C alone caused almost no cell killing to IMC-3 and IMC-3-DDP cells. In both cell lines, the dose-dependent cytotoxicity of 2-h exposures to CDDP was increased at 40 degrees C in comparison to 37 degrees C. Heating at 40 degrees C also potentiated CDDP cytotoxicity in both IMC-3 and IMC-3-DDP cells with thermal chemoenhancement ratios (CER) of 1.48 and 1.94, respectively. The intracellular CDDP uptake level of IMC-3-DDP at 37 degrees C was significantly reduced compared with IMC-3 cells. At 40 degrees C, however, hyperthermia increased platinum accumulation by factors of 1.4 and 1.8 in IMC-3 and IMC-3-DDP cells, respectively. These findings indicated that CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants rather than in the control clones. Thus, clinical cancer chemotherapy with CDDP may be improved by an appropriate combination with hyperthermia even at 40 degrees C.

Inhibitory effects of selenium, vitamin A and butylated hydroxytoluene on growth of human maxillary cancer cells in vitro.

The effects of vitamin A, selenium, and butylated hydroxytoluene (BHT) on the growth of a human maxillary cancer cell line were examined in monolayer cell cultures. The colony-forming assay showed a 50% reduction in the survival rate of the cell line at a concentration of 3.6 micrograms/ml of selenium, 28 micrograms/ml of vitamin A, and 74 micrograms/ml of BHT. Flow cytometric analysis with both FITC-labeled bromodeoxyuridine monoclonal antibody and propidium iodide demonstrated an increase of the S-phase fraction in the presence of selenium, an increase of the G0/G1-phase fraction in the presence of vitamin A, and an increase of the G2-M-phase fraction 1 day followed by an increase of G0/G1-phase fraction from the 3rd to 7th day when BHT was added. These results suggest that the mechanisms of inhibition of DNA synthesis by these compounds are different.

Application of the ATP-bioluminescence assay to thermosensitivity testing for head and neck cancer.

We investigated the usefulness of the ATP assay as a thermosensitivity test in comparison with a colony-forming assay (CFA). The intracellular ATP levels in KB cells were markedly decreased after exposure to hyperthermia (43 degrees C for 1 h), reaching less than half that in the control cells in 12-18 h, and recovering gradually thereafter. The effect of hyperthermia assessed by the ATP assay closely correlated to that assessed by CFA, not only when KB cells were heated at 42, 43, and 44 degrees C but also in the conditions where L, KB and IMC-3 cell lines were heated at 43 degrees C. Findings showed that the ATP assay can be performed easily and more quickly than CFA for evaluating cell viability after heating. We also investigated heterogeneous responses to hyperthermia in cells from fresh surgical specimens of tumors. Thus, this rapid and reliable test was found to be useful for predicting the outcome of hyperthermia as a clinical treatment.

Synergistic effects of irradiation and hyperthermia on established cell lines derived from maxillary carcinoma. Report II.

We studied in vitro the capability of radiation, hyperthermia, and their combination to inhibit growth of cell strains isolated from maxillary carcinoma and their radiation tolerant strains. Synergic effects of the combination were studied by investigating effects of hyperthermia and radiation on cell cycles with BrdU pulse labelling to establish optimal conditions for the combination. Growth of cell strains from maxillary carcinoma was remarkably inhibited by thermal treatment because of retarded cellular cycles. Cells at the S-phase were so sensitive to heat that their intake of BrdU was debilitated. Radiation increased the proportion of cells at the S-phase that poorly synthesized DNA. When combining radiation with hyperthermia, the heat killed cells at the S-phase, which was prolonged by radiation, and survivors showed retarded cellular cycles; that is, synergism was found.

Synergistic effect of irradiation and hyperthermia on established cell lines derived from maxillary carcinoma. Report I.

Cultured tumor cells of an established cell line derived from cancer of the head and neck (maxillary and lingual cancer) were irradiated with X-rays (5 or 10 Gy). This treatment inhibited cell proliferation in a dose-dependent way. Cell cycle analysis showed that the ratio of cells in the S phase to the population of viable cells was higher than that in a non-irradiated control group. Thus, the S phase was prolonged by exposure to X-rays. Cell proliferation was also inhibited by 1 h of heat treatment at 43 degrees C. However, movement through the cell cycle was slowed down overall and no cell aggregation in any phase of the cell cycle was found. Proliferation of not only radioresistant but also radiosensitive cells was inhibited by this treatment. Hyperthermia at 43 degrees C for 1 h did not affect cell proliferation, nor did it influence the pattern of cell cycle distribution. However, it caused a decrease in intracellular polyamine amount. The combination of irradiation and hyperthermia caused a stronger inhibition than either treatment alone. The synergistic effect of the two treatments probably arose from the S-phase cells being heat-labile although radioresistant.

An ancient "tumour" from pre-Columbian Chile.

A case of an expansile facial lesion discovered in the more than 600 years old skeletal remains of a 22-25-year-old female is discussed. Gross, radiographic and histological studies were accomplished on the specimen. Although a definitive diagnosis could not be derived because of the age and condition of the specimen, differential diagnoses are discussed and a probable diagnosis rendered.