Efficacy of Episil® in patients with hematologic malignancies: a comparative study.

BACKGROUND: Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome. METHODS: Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital). RESULTS: Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis. CONCLUSIONS: This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Relationship of oral bacterial number with medical hospitalization costs in analysis of Diagnosis Procedure Combination database from single institution in Japan.

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.

Efficacy of Low-Level Laser Therapy for Oral Mucositis in Hematologic Patients Undergoing Transplantation: A Single-Arm Prospective Study.

Oral mucositis significantly affects the quality of life in hematologic cancer patients undergoing hematopoietic stem cell transplantation. Despite global evidence supporting the efficacy of low-level laser therapy (LLLT) for mucositis prevention, its clinical adoption in Japan is limited. This study aimed to fill this gap by evaluating the safety and efficacy of LLLT in a Japanese patient population. In a single-group, non-blinded, exploratory trial, we compared 21 LLLT-treated patients against a historical control of 96 patients. The primary endpoint was the incidence of Grade ≥ 2 mucositis, based on NCI-CTCAE ver. 4.0. The LLLT group showed a significantly lower incidence of Grade ≥ 2 mucositis (23.8%) compared to the control group (64.6%) (p = 0.0006). Furthermore, Grade ≥ 2 mucositis correlated with increased oral dryness and longer hospital stays. Our study confirms the efficacy of LLLT in reducing the onset of severe oral mucositis among Japanese hematologic cancer patients, advocating for its clinical introduction as a preventive measure in Japan.

Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with recurrent oral squamous cell carcinoma treated with nivolumab.

The immune checkpoint inhibitor (ICI), nivolumab, has revolutionised the treatment of recurrent and metastatic oral cancer. However, the response rate to ICIs remains low, and identifying predictors of nivolumab response is critical. Although the neutrophil-to-lymphocyte ratio (NLR) has been suggested as a predictive marker of nivolumab response in patients with various types of cancer, its utility in oral squamous cell carcinoma (OSCC) has not been elucidated. In this retrospective multicentre cohort study, we evaluated the association between NLR and outcome of nivolumab treatment in 64 patients with OSCC treated between 2017 and 2020. The objective response and disease control rates were 25.1% and 32.9%, respectively. The rates for complete and partial responses were 15.7% (10/64) and 9.4% (6/64), respectively; stable and progressive disease rates were 7.8% (5/64) and 67.1% (43/64), respectively. Complete and partial responses were classified as responders, and stable and progressive diseases were classified as non-responders. The median (range) pre-treatment NLR among responders was 4.3 (2.8-8.0), which decreased to 4.0 (2.6-6.3) after nivolumab treatment, and the median (range) pre-treatment NLR among non-responders was 5.1 (2.7-7.9), which increased to 6.4 (4.0-14.0) with tumour growth. Moreover, overall survival was significantly worse in the group with a higher post-treatment NLR (≥5) than in the group with a lower NLR (<5). Patients with a post-treatment NLR of ≥6 had worse outcomes for salvage chemotherapy following nivolumab treatment. Thus, post-treatment NLR could be a useful marker for predicting the response to nivolumab treatment or salvage chemotherapy in patients with OSCC.

Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors.

BACKGROUND: While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. METHODS: A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. RESULTS: During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/µL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). CONCLUSION: Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

VEGF-A promotes the motility of human melanoma cells through the VEGFR1-PI3K/Akt signaling pathway.

Vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1 and R2) play important roles in the progression of malignant melanoma through tumor angiogenesis. However, it is not clear whether the VEGF-A/VEGFR1 signaling pathway is involved in the proliferation and migration of melanoma cells. Thus, the effect of VEGF-A on cell migration was investigated in human melanoma cell lines. Of several splicing variants of VEGF-A, VEGF165 is the most abundant and responsible for VEGF-A biological potency. VEGF165 facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF165. VEGF165 also induced the phosphorylation of Akt. In addition, VEGF165-induced cell migration was inhibited significantly by VEGFR1/2 or a VEGFR1-neutralizing antibody. Furthermore, the downregulation of VEGFR1 via the transfection of VEGFR1-targeting antisense oligonucleotides suppressed VEGF165-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF165-induced Akt phosphorylation and VEGF165-induced cell migration. These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF165. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma.

Development of a radiomics and machine learning model for predicting occult cervical lymph node metastasis in patients with tongue cancer.

OBJECTIVE: We aimed to develop a predictive model for occult cervical lymph node metastasis in patients with tongue cancer using radiomics and machine learning from pretreatment contrast-enhanced computed tomography. STUDY DESIGN: This study included 161 patients with tongue cancer who received local treatment. Computed tomography images were transferred to a radiomics platform. The volume of interest was the total neck node level, including levels Ia, Ib, II, III, and IVa at the ipsilateral side, and each neck node level. The dimensionality of the radiomics features was reduced using least absolute shrinkage and selection operator logistic regression analysis. We compared 5 classifiers with or without the synthetic minority oversampling technique (SMOTE). RESULTS: For the analysis at the total neck node level, random forest with SMOTE was the best model, with an accuracy of 0.85 and an area under the curve score of 0.92. For the analysis at each neck node level, a support vector machine with SMOTE was the best model, with an accuracy of 0.96 and an area under the curve score of 0.98. CONCLUSIONS: Predictive models using radiomics and machine learning have potential as clinical decision support tools in the management of patients with tongue cancer for prediction of occult cervical lymph node metastasis.

Periodontal inflamed surface area in oral cavity associated with febrile neutropenia in patients with hematologic malignancy undergoing chemotherapy.

Febrile neutropenia (FN) is an infectious complication that develops during chemotherapy. Although the oral cavity can be an important infection route, it is unknown whether the oral environment is associated with FN. The present study examined the relationship between the oral environment using periodontal inflamed surface area (PISA), a new periodontal disease parameter, and FN in hematologic cancer patients undergoing chemotherapy. In this retrospective cohort study, 157 patients were divided into FN onset during chemotherapy (n = 75) and the FN negative groups (n = 82). The associations of risk factors related to the intraoral environment were assessed. Logistic regression analysis showed that types of blood cancer (odds ratio 1.98; P < 0.01), use of a high-risk regimen (odds ratio 4.44; P < 0.05), prophylaxis treatment with human granulocyte colony-stimulating factor (G-CSF) (odds ratio 4.15; P < 0.01) and PISA (odds ratio 1.02; P < 0.01) were independent factors associated with FN onset. Finally, propensity score matching was performed between two groups; 37 matched pairs were generated. PISA was significantly higher in the FN group than the FN negative group. There was a significant relationship between PISA and FN onset (P = 0.035). The present findings indicate that periodontitis treatment before starting cancer treatment is recommended as supportive care for preventing FN onset during chemotherapy.

Impact of Maximum Tongue Pressure in Patients with Jaw Deformities Who Underwent Orthognathic Surgery.

Malocclusion and morphological abnormalities of the jawbone often affect the stomatognathic function and long-term postoperative stability in patients with jaw deformities. There are few reports on the effect of maximum tongue pressure (MTP) in these patients. We investigated the relationship between the MTP and jawbone morphology and the effect of the MTP on surgery in 42 patients with jaw deformity who underwent surgical orthodontic treatment at Hiroshima University Hospital. The MTP was measured using a tongue pressure measurement device; the average value was considered as the MTP. Based on the MTP measured before surgery, patients were classified into the high- or the low-MTP group. The clinical findings and results of the cephalometric analysis were compared. Posterior movement of the mandible in the high-MTP group was significantly lower than that in the low-MTP group. The ANB angle, overjet, and overbite in the high-MTP group were significantly smaller than those in the low-MTP group. On the other hand, there was no difference between the two groups in the measured values, indicating a labial inclination of the anterior teeth (U1 to SN, U1 to FH, IMPA, and FMIA). MTP has been suggested to affect mandibular prognathism in patients with jaw deformities.

Relationships between intraoral ultrasonographic and histopathological findings in patients with tongue cancer.

BACKGROUND: In this study, we aimed to investigate the relationships between histopathological and intraoral ultrasonographic (IUS) findings in patients with tongue cancer. METHODS: IUS and histopathological findings in 46 patients with tongue cancer were considered for this study. We assessed the relationships between IUS findings regarding tumor thickness, margin type, border type, and internal echo intensity; internal/peripheral Doppler findings; and muscle invasion and histopathological findings regarding tumor thickness, differentiation, Yamamoto-Kohama (YK)-classification grade, blood vessel invasion, lymphatic invasion, perineural invasion, and muscle invasion. RESULTS: Statistical associations were found between the following findings: between thickness determined through IUS measurement and that determined through histopathological measurement, between the IUS findings regarding tumor margin and border types and the histopathologically determined YK-classifications grades, and between a Doppler image of the internal area of tongue lesions and lymphatic invasion. CONCLUSIONS: IUS findings may be used to predict histopathological findings about tumor thickness and YK-classification grades.

Enhanced KRT13 gene expression bestows radiation resistance in squamous cell carcinoma cells.

Cancer metastasis and recurrence are potentially lethal. A small number of cancer cell groups called cancer stem cells (CSCs) have both stem cell capacity and cancer-forming ability and are reported to play important roles in cancer metastasis and recurrence. These CSCs are considered to be radiation-resistant (RR). Therefore, understanding the biological effects of radiation on squamous cell carcinoma (SCC) cell lines in vitro and in vivo might be worthwhile to circumvent radiation resistance. Currently, there are no reports on the establishment of RR-SCC cells in serum-free defined culture, which mimics biological mechanisms and prevents instability of using serum in the culture medium. We isolated radiation-resistant strains, designated A431-LDR and A431-HDR, from A431 cells derived from vulval SCC and irradiated them with a total dose of 60 Gy at a low-dose rate (2.2 Gy/d) (RM1000) and a high-dose rate (5 Gy/5.75min) in serum-free defined culture. These cells exhibited high sphere-forming and migration ability in vitro and high tumor-forming ability in nude mice xenografts. Overexpression of KRT13 in A431-RR cells might play a role in its radiation-resistant characteristics. These cells might be useful not only to study cancer stem cells but also to study the circumvention of radiation resistance by novel cancer treatment modalities.

Effects of perioperative oral care on postoperative inflammation following heart valve surgery.

OBJECTIVE: Whether oral health care during the perioperative period can lead to a better outcome after heart valve surgery has not been adequately elucidated. We examined the effects of perioperative oral care on postoperative inflammation response in patients who underwent heart valve surgery. MATERIALS AND METHODS: In this retrospective cohort study, 223 patients scheduled for single valve heart surgery were divided into the oral care, who underwent professional teeth cleaning or scaling within 3 days prior to surgery, and also following surgery at least twice a week (n = 111), and non-oral care (n = 112) groups. After propensity score matching, records of both groups (80:80) were examined after surgery to evaluate inflammation markers (white blood cell count [WBC], neutrophil/white blood cell ratio [NWR], C-reactive protein [CRP] level, body temperature [BT]). RESULTS: WBC, NWR, CRP level, and BT were increased in both groups the day following surgery. Thereafter, CRP level, WBC, NWR, and BT on various days after surgery in the oral care group showed greater decreases as compared to the non-oral care group. CONCLUSIONS: Perioperative oral health care can decrease postoperative inflammation in patients undergoing heart valve surgery and may be important to ensure a better outcome in those patients.

Reconstruction of an upper lip and intraoral defect following resection of an upper lip melanoma using a lower lip musculomucosal flap combined with a tongue flap.

Restoring the cosmetic and functional aspects of the lip after tumor resection is challenging. We report a case of reconstruction for a defect due to resection of a melanoma using a lower lip musculomucosal flap combined with a tongue flap. A 20-year-old man was referred to our hospital and diagnosed with malignant melanoma with metastatic right submaxillary lymph nodes. We excised the tumor with neck dissection. We excised not only the right upper lip mucosa but also the gum, including some orbicularis oris muscle and alveolar bone from the right canine tooth to the left central incisor tooth. The defect was simultaneously reconstructed using both, a lower lip musculomucosal flap and a tongue flap. Revisional operation to remove contraction of a postoperative scar and the right vermillion border collection was performed at 3 months after the initial operation. There had been no functional and cosmetic trouble of the upper lip.

Suture granulomas developing after the treatment of oral squamous cell carcinoma.

INTRODUCTION: Suture granuloma is a benign tumor that develops because of the presence of surgical suture materials. It commonly occurs several years after different types of surgeries. Here we report a case involving a 64-year-old man who underwent head and neck surgery for oral squamous cell carcinoma and developed multiple suture granulomas mimicking tumor recurrence in the radiation field just a few days after the completion of adjuvant chemoradiation therapy. PRESENTATION OF CASE: The patient underwent surgery for lymph node metastasis in the neck at 6 months after the resection of primary oral squamous cell carcinoma. Fifteen days after the completion of adjuvant chemoradiation therapy at a total dose of 50 Gy, small nodules appeared in the radiation field, along the areas of the subcutaneous surgical sutures. Cancer recurrence was initially suspected, but histopathological analysis of a biopsy specimen confirmed foreign body granuloma. DISCUSSION: Chemoradiation therapy may enhance the immunoreaction of macrophages in the radiation field and promote the formation of granulation tissue in a short period of time. In addition, cisplatin, which was concurrently administered with radiation in our case, could have influenced the development of the suture granuloma. CONCLUSION: In addition to tumor recurrence, suture granulomas should be considered a differential diagnosis for nodules occurring after surgery, even if they develop in the field of radiation.

New Crambescidin-Type Alkaloids from the Indonesian Marine Sponge Clathria bulbotoxa.

A crude methanolic extract of the Indonesian sponge Clathria bulbotoxa showed a potent cytotoxic activity against the human epidermoid carcinoma A431 cells. An investigation of the active components led to the isolation of three new compounds named crambescidins 345 (1), 361 (2), and 373 (3), together with the known related metabolites crambescidins 359 (4), 657 (5), and 800 (6). The structures of the compounds were determined by spectroscopic analysis. These compounds 1-4 that possess a simple pentacyclic guanidine core exhibited moderate cytotoxicity against the A431 cells with the IC50 values of 7.0, 2.5, 0.94, and 3.1 µM, respectively, while the known compounds 5 and 6 that possess a long aliphatic side chain were found to be significantly cytotoxic. On the other hand, in an anti-oomycete activity test against the fungus-like plant pathogen Phytophthora capsici, 1-4 showed a higher activity than that of 5 and 6, suggesting that the long aliphatic side chain plays a significant role for cytotoxicity, but is not effective or suppressive for anti-oomycete activity.

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up.

OBJECTIVES: Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. MATERIALS AND METHODS: Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2mg/kg) intravenously 48h prior to light irradiation. Photoradiation was performed at doses of 100-150J/cm(2) using a 630-nm wavelength excimer dye laser. RESULTS: Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. CONCLUSION: PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.

Ectomesenchymal chondromyxoid tumor of the tongue: insights on histogenesis.

OBJECTIVE: The objective of this study was to investigate the histogenesis of ectomesenchymal chondromyxoid tumors (ECTs) of the tongue. STUDY DESIGN: The biochemical characteristics of a rarely occurring tumor of the tongue were analyzed by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR), and its biological properties were assessed in primary culture in serum-free media. RESULTS: Immunohistochemistry showed that the tumor cells were strongly positive for vimentin, S-100, and glial fibrillary acidic protein (GFAP), but negative for cytokeratin and epithelial membrane antigen. In primary cultures, the cells derived from the ECT were morphologically similar to neuronal cells and expressed Nanog, GFAP, and MAP2. RT-PCR analysis of the surgical specimen was positive for OCT3/4, Sox2, Nanog, MAP2, and CD105 mRNAs. CONCLUSIONS: The results of the present study indicate that ECTs originate from the ectomesenchymal cells of the neural crest and are similar in their molecular and biological characteristics to undifferentiated mesenchymal stem cells.

Ameloblastic carcinoma, secondary type, of the mandible: a case report.

Ameloblastic carcinoma is a rare, odontogenic, malignant tumor that has features of ameloblastoma in addition to cytologic atypia with or without metastasis. It is classified as primary type; secondary type, intraosseous; and secondary type, peripheral according to the World Health Organization classification of 2005. Ameloblastic carcinoma, secondary type, is extremely rare, and few cases have been reported in the English-language literature. The authors report a case of ameloblastic carcinoma, secondary type, arising at the mandible in a 17-year-old Japanese boy.

Novel cytotoxic polyoxygenated steroids from an Okinawan sponge Dysidea sp.

A library of extracts established from hundreds of marine organisms was screened by a cytotoxicity test. The active organic extract of an Okinawan marine sponge of the genus Dysidea was subjected to bioassay-guided fractionation to give three new polyoxygenated steroids dysideasterols F-H (1-3), together with two known related compounds (4 and 5). Their structures were confirmed by NMR and mass spectroscopic analyses. A characteristic structural feature of 2, 4 and 5 is an allylic epoxide, whereas this epoxide undergoes ring-opening by a neighbouring hydroxyl group to give a tetrahydrofuran ring in 1 and 3. All compounds 1-5 exhibited a similar cytotoxic effect with IC50 values of 0.15-0.3 µM against human epidermoid carcinoma A431 cells, demonstrating that the allylic epoxide moiety was not responsible for this cytotoxic effect.