Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

Cost of illness for colorectal cancer in Japan - a time trend and future projections (1996-2035) based on governmental statistics.

BACKGROUND: In Japan, the crude mortality rate of colorectal cancer is the second highest among men and highest among women by site. We aimed to calculate the social burden of colorectal cancer using the cost of illness (COI) method and identify the main factors that drove changes in the COI. METHODS: From 1996 to 2020, the COI was estimated by summing direct, morbidity, and mortality costs. In addition, the COI by 2035 was projected by fitting approximate curves obtained from historical data to health-related indicators by sex and age. Future projections of the number of patients by the stage of disease were also made to explore the factors that changed the COI. RESULTS: The number of deaths and incidence from colorectal cancer was expected to continue increasing due to population aging. However, the COI was projected to rise from 850.3 billion yen in 1996 to 1.451 trillion yen in 2020, and peaked at 1.478 trillion yen in 2023 before it declined. CONCLUSION: Although the increased number of deaths associated with population aging increased COI, it was expected that the COI would decrease around 2023 due to a decrease in the human capital value of the deceased. In addition, the mortality rate was expected to decrease in the future due to an increase in the percentage of early detection of colorectal cancer via widespread screening and advances in medical technology.

Primary syphilis with a tongue ulcer mimicking tongue cancer: a case report.

The main symptom in primary syphilis is a small, painless, sore or ulcer called a chancre on the penis, vagina, or around the anus, although chancres can sometimes appear in the mouth or on the lips, fingers, or buttocks. We present the case of a man in his early 60 s with a chief complaint of a painful tongue ulcer. An ulcerated, indurated, and hemorrhagic lesion (23 × 14 mm) was found on the ventral tongue surface, near the oral floor. Palpation identified several swollen, mobile, elastic cervical lymph nodes, with no tenderness. We initially diagnosed tongue cancer; however, during a subsequent detailed examination for a malignant tumor, including biopsy and obtaining additional history, his disease was finally identified as primary syphilis with multiple swollen cervical lymph nodes. Oral amoxicillin and probenecid were started, and after 14 days, there was partial reduction in the size of the submandibular lymph nodes and the ulcer on the left tongue margin. The number of patients with syphilis in Japan increased by eight times from 2012 to 2018. We suggest that dentists consider primary syphilis as a differential diagnosis for oral refractory ulcer with induration and obtain a detailed patient history.

Social burden of three major diseases in Japan: A time trend and future projections using the comprehensive cost of illness method.

BACKGROUND: Three major diseases in Japan, cancer, heart disease, and cerebrovascular disease (CVD) are the leading causes of death in Japan. This study aimed to clarify the social burden of these diseases, including long-term care (LTC), and to predict future trends. METHODS: The comprehensive cost of illness (C-COI), a modification of the cost of illness (COI), was used to estimate the social burden of the three major diseases in Japan. The C-COI can macroscopically estimate both direct and indirect costs, including the LTC. A new method for future projections of the C-COI was developed according to the method for future projections of the COI. All data sources were government statistics. RESULTS: The C-COI of cancer, heart diseases, and CVD in 2017 amounted to 11.0 trillion JPY, 5.3 trillion JPY, and 6.5 trillion JPY, respectively. The projected future C-COI in 2029 was 10.3 trillion JPY, 5.3 trillion JPY, and 4.4 trillion JPY, respectively. In 2029, the LTC costs accounted for 4.4%, 12.8%, and 44.1% of the total C-COI, respectively. Informal care costs are projected to be approximately 1.7 times higher, assuming that all family caregivers will be replaced by professional caregivers in 2029. CONCLUSION: Indirect costs for all three diseases were projected to decrease owing to aging of the patient. In contrast to the other two diseases, the LTC cost of CVD accounted for a large proportion of the burden. The burden of CVD is expected to decrease in the future, but informal care by older family caregivers is suggested to reach its limits. In the future, the focus of resource allocation should shift from medical care to LTC, especially support for family caregivers. A method of future projections for the social burden based on the C-COI was considered effective for identifying issues for healthcare policy in the context of the times.

Cost of illness in a super-aged society-comparison of breast, lung, and prostate cancer in Japan.

BACKGROUND: Aging increases the disease burden because of an increase in disease prevalence and mortality among older individuals. This could influence the perception of the social burden of different diseases and treatment prioritization within national healthcare services. Cancer is a disease with a high disease burden in Japan; however, the age-specific frequency and age-specific mortality rates differ according to site. In this study, we evaluated the relationship between the aging of the Japanese society and the disease burden by comparing the features of three cancers with different age-specific frequency rates in Japan. Furthermore, we made projections for the future to determine how the social burden of these cancers will change. METHODS: We calculated the social burden of breast, lung, and prostate cancers by adding the direct, morbidity, and mortality costs. Estimates were made using the cost of illness (COI) method. For future projections, approximate curves were fitted for mortality rate, number of hospital admissions per population, number of outpatient visits per population, and average length of hospital stay according to sex and age. RESULTS: The COI of breast, lung, and prostate cancers in 2017 was 903.7, 1,547.6, and 390.8 billion yen, respectively. Although the COI of breast and prostate cancers was projected to increase, that of lung cancer COI was expected to decrease. In 2017, the average age at death was 68.8, 76.8, and 80.7 years for breast, lung, and prostate cancers, respectively. CONCLUSIONS: Patients with breast cancer die earlier than those with other types of cancer. The COI of breast cancer ("young cancer") was projected to increase slightly because of an increase in mortality costs, whereas that of prostate cancer ("aged cancer") was projected to increase because of an increase in direct costs. The COI of lung cancer ("aging cancer") was expected to decrease in 2020, despite the increase in deaths, as the impact of the decrease in human capital value outweighed that of the increase in deaths. Our findings will help prioritize future policymaking, such as cancer control research grants.

The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications.

Mutations in p53 are common in human oral squamous cell carcinoma (OSCC). However, in previous analyses, only detection of mutant p53 protein using immunohistochemistry or mutations in some exons have been examined. Full length mutant p53 protein in many cases shows a loss of tumor suppressor function, but in some cases possibly shows a gain of oncogenic function. In this study, we investigate relationships of outcomes with the mutational spectrum of p53 (missense and truncation mutations) in whole exon in OSCC. Specimens from biopsy or surgery (67 cases) were evaluated using next-generation sequencing for p53, and other oncogenic driver genes. The data were compared with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analyses. p53 mutations were detected in 54 patients (80.6%), 33 missense mutations and 24 truncation mutations. p53 mutations were common in the DNA-binding domain (43/52) and many were missense mutations (31/43). Mutations in other regions were mostly p53 truncation mutations. We detected some mutations in 6 oncogenic driver genes on 67 OSCC, 25 in NOTCH1, 14 in CDKN2A, 5 in PIK3CA, 3 in FBXW7, 3 in HRAS, and 1 in BRAF. However, there was no associations of the p53 mutational spectrum with mutations of oncogenic driver genes in OSCC. A comparison of cases with p53 mutations (missense or truncation) with wild-type p53 cases showed a significant difference in lymph node metastasis. DFS was significantly poorer in cases with p53 truncation mutations. Cases with p53 truncation mutations increased malignancy. In contrast, significant differences were not found between cases with p53 missense mutations and other mutations. The p53 missense mutation cases might include cases with mostly similar function to that of the wild-type, cases with loss of function, and cases with various degrees of gain of oncogenic function.

Surveillance for Patients with Oral Squamous Cell Carcinoma after Complete Surgical Resection as Primary Treatment: A Single-Center Retrospective Cohort Study.

BACKGROUND: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance of patients with OSCC based on the individual risk for recurrence and/or metastasis, we performed a retrospective cohort study after the complete surgical resection of OSCC as the primary treatment. METHODS: The study was performed in 324 patients with OSCC who had been primarily treated with surgery from 2007 to 2020 at our hospital. We investigated the period, timing, and methods (visual examination, palpation and imaging using FDG-PET/CT or CECT) for surveillance in each case that comprised postsurgical treatment. RESULTS: Regarding the time to occurrence of postsurgical events, we found that half of cases of local recurrence, cervical lymph node metastasis, and distant metastasis occurred within 200 days, and 75% of all of these events occurred within 400 days. However, the mean time for second primary cancer was 1589 days. The postsurgical events were detected earlier by imaging examinations than they were by visual examination and palpation. CONCLUSIONS: For the surveillance of patients with OSCC after primary surgery, it is desirable to perform FDG-PET/CT within 3-6 months and at 1 year after surgery and to consider CECT as an option in between FDG-PET/CT, while continuing history and physical examinations for about 5 years based on individual risk assessment.

Morphometric and histomorphometric evaluations of high-purity macro/microporous beta-tricalcium phosphate in maxillary sinus floor elevation: preliminary results on a retrospective, multi-center, observational study.

BACKGROUND: The present study examined the effectiveness of high-purity macro/microporous beta-tricalcium phosphate (HPMM ß-TCP) as a bone grafting material for maxillary sinus floor elevation by morphometric, histopathological, and histomorphometric evaluations. METHODS: Ten unilateral maxillary sinus floor elevation procedures using 100% HPMM ß-TCP were performed in 10 patients. Morphometric evaluation was carried out by computed tomography (CT) imaging immediately after augmentation and prior to dental implant placement 7 months later. Histopathological and histomorphometric evaluations were carried out by bone biopsy retrieval at the time of dental implant placement 7 months after sinus floor elevation. RESULTS: All 10 sinus floor elevations were successful. Morphometric evaluation by CT showed that the vertical height and volume gained by sinus floor elevation decreased 7 months after surgery. Histopathological evaluation of bone biopsy retrieval specimens showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. New bone formation was observed at the cranial side from the native alveolar bone. The newly formed bone had a trabecular structure and was in intimate contact with the HPMM ß-TCP material. Histomorphometric evaluation of bone biopsy retrieval specimens showed an average new bone volume of 33.97% ± 2.79% and an average residual HPMM ß-TCP volume of 15.81% ± 4.52%. CONCLUSIONS: In this study, HPMM ß-TCP showed osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period.

Oral squamous cell carcinoma may originate from bone marrow-derived stem cells.

Molecules that demonstrate a clear association with the aggressiveness of oral squamous cell carcinoma (OSCC) have not yet been identified. The current study hypothesized that tumor cells in OSCC have three different origins: Epithelial stem cells, oral tissue stem cells from the salivary gland and bone marrow (BM) stem cells. It was also hypothesized that carcinomas derived from less-differentiated stem cells have a greater malignancy. In the present study, sex chromosome analysis by fluorescence in situ hybridization and/or microdissection PCR was performed in patients with OSCC that developed after hematopoietic stem cell transplantation (HSCT) from the opposite sex. OSCC from 3 male patients among the 6 total transplanted patients were considered to originate from donor-derived BM cells. A total of 2/3 patients had distant metastasis, resulting in a poor prognosis. In a female patient with oral potentially malignant disorder who underwent HSCT, there were 10.7% Y-containing cells in epithelial cells, suggesting that some epithelial cells were from the donor. Subsequently, gene expression patterns in patients with possible BM stem cell-derived OSCC were compared with those in patients with normally developed OSCC by microarray analysis. A total of 3 patients with BM stem cell-derived OSCC exhibited a specific pattern of gene expression. Following cluster analysis by the probes identified on BM stem cell-derived OSCC, 2 patients with normally developed OSCC were included in the cluster of BM stem cell-derived OSCC. If the genes that could discriminate the origin of OSCC were identified, OSCCs were classified into the three aforementioned categories. If diagnosis can be performed based on the origin of the cancer cells, a more specific therapeutic strategy may be implemented to improve prognosis. This would be a paradigm shift in diagnostic and therapeutic strategies for OSCC.

Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single-center retrospective cohort study.

A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028; CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05-0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053-1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.

Cost of illness of liver diseases in Japan.

INTRODUCTION AND OBJECTIVES: Liver disease is characterized by the progression from hepatitis to cirrhosis, followed by liver cancer, i.e., a disease with a higher mortality rate as the disease progresses. To estimate the cost of illness (COI) of liver diseases, including viral hepatitis, cirrhosis, and liver cancer, and to determine the overall effect of expensive but effective direct-acting antivirals on the COI of liver diseases. PATIENTS OR MATERIALS AND METHODS: Using a COI method from available government statistics data, we estimated the economic burden at 3-year intervals from 2002 to 2017. RESULTS: The total COI of liver diseases was 1402 billion JPY in 2017. The COI of viral hepatitis, cirrhosis, and liver cancer showed a downward trend. Conversely, other liver diseases, including alcoholic liver disease and nonalcoholic steatohepatitis (NASH), showed an upward trend. The COI of hepatitis C continued to decline despite a sharp increase in drug unit prices between 2014 and 2017. CONCLUSIONS: The COI of liver diseases in Japan has been decreasing for the past 15 years. In the future, a further reduction in patients with hepatitis C is expected, and even if the incidence of NASH and alcoholic liver disease increases, that of cirrhosis and liver cancer will likely continue to decrease.

Comparison of the cost of illness of primary liver cancer between Japan and Taiwan.

BACKGROUND: Primary liver cancer (PLC) is the fifth and second leading cause of death in Japan and Taiwan, respectively. The aim of this study was to compare the economic burden of PLC between the two countries using the cost of illness (COI) method and identify the key factors causing the different trends in the economic burdens of PLC. MATERIALS AND METHODS: We calculated the COI every 3 years using governmental statistics of both countries (1996-2014 data for Japan and 2002-2014 data for Taiwan). The COI was calculated by summing the direct costs, morbidity costs, and mortality costs. We compared the COIs of PLC in both countries at the USD-based cost. The average exchange rate during the targeted years was used to remove the impact of foreign exchange volatility. RESULTS: From 1996 to 2014, the COI exhibited downward and upward trends in Japan and Taiwan, respectively. In Japan, the COI in 2014 was 0.70 times the value in 1996, and in Taiwan, the COI in 2014 was 1.16 times greater than that in 1996. The mortality cost was the greatest contributor in both countries and had the largest contribution ratio to the COI increase in Japan. However, the direct cost in Taiwan had the largest contribution ratio to the COI decrease. CONCLUSIONS: To date, the COI of PLC in Japan has continuously decreased, whereas that in Taiwan has increased. Previous health policies and technological developments are thought to have accelerated the COI decrease in Japan and are expected to change the trend of COI of PLC, even in Taiwan.

Whole Exome Sequencing of SMO, BRAF, PTCH1 and GNAS in Odontogenic Diseases.

BACKGROUND/AIM: Odontogenic diseases are diagnosed based on clinical course, imaging, and histopathology. However, a definitive diagnosis is not always possible. PATIENTS AND METHODS: We analyzed whole exons of SMO, BRAF, PTCH1 and GNAS using next-generation sequencing (NGS) in 18 patients. RESULTS: Of the 6 patients with ameloblastoma, 2 patients had the same missense mutation in BRAF, and 1 patient with peripheral ameloblastoma had a missense mutation in PTCH1. Of the 7 patients with odontogenic keratocyst, 4 patients had a missense mutation in PTCH1, 2 patients had missense mutations in BRAF, and 1 patient had a missense mutation in SMO. The patient with odontoma had missense mutations in SMO, BRAF and PTCH1. One patient with cement-osseous dysplasia had missense mutations in SMO and PTCH1. The patient with adenomatoid odontogenic tumor had missense mutations in SMO. CONCLUSION: Whole exome sequencing of the above genes by NGS would be useful for the differential diagnosis of odontogenic diseases.

Clinical characteristics, treatment methods and prognoses of patients with oral squamous cell carcinoma in Japanese population: a single institution retrospective cohort study.

BACKGROUND: The status of oral cancer therapy in elderly patients in Japan, where ageing is rapidly progressing, may serve as a model for other countries with similar demographics. There is controversy over what kind of treatment should be applied and how aggressively it should be applied to very elderly patients who have exceeded the average life expectancy. Given that 85 years is approximately the overall Japanese life expectancy at birth, we considered a threshold of 85 years and hypothesized that the prognosis of oral squamous cell carcinoma (SCC) patients aged ≥85 years was not inferior to that of those < 85 years. The aim of the present study was to investigate the clinical characteristics, treatment methods, and prognoses of Japanese oral SCC patients aged ≥85 years. METHODS: A retrospective cohort study was performed. The data of patients with primary oral SCC (n = 358) from 2005 to 2018 in our institute were extracted from electronic medical records. A total of 358 patients with oral SCC were divided into two groups (≥85 years group [n = 26] and < 85 years group [n = 332]) based on the age threshold of 85 years at the first visit. Kaplan-Meier survival analyses and Cox proportional hazard models were used to analyse overall survival (OS) and hazard ratios (HRs) according to age group, treatment, and TNM classification. RESULTS: There was no difference in the 5-year OS rate between the ≥85 years and < 85 years groups (80.8% vs. 82.2%, P = 0.359). This finding was the same in the operative (94.7% vs. 85.8%, P = 0.556) and non-operative (42.9% vs. 33.2%, P = 0.762) groups, indicating that age did not affect prognosis. Mortality was lower in the operative group than in the non-operative group (adjusted HR: 0.276, 95% CI: 0.156-0.489, P < 0.001), suggesting that surgery is a superior method. However, non-surgical treatment was selected at a higher rate in the ≥85 years group (26.9% vs. 11.1%, P = 0.028). CONCLUSIONS: This study suggests the prognosis of ≥85-year-old patients was not inferior to that of < 85-year-old patients. We recommend that surgery as the first choice treatment for ≥85-year-old patients with oral SCC who can tolerate surgery should be performed.

Paclitaxel Potentiates the Anticancer Effect of Cetuximab by Enhancing Antibody-Dependent Cellular Cytotoxicity on Oral Squamous Cell Carcinoma Cells In Vitro.

Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells.

Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment-resistant major depressive disorder.

AIM: A substantial proportion of major depressive disorder patients are treatment-resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment-resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment-resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment-resistant major depressive disorder. METHOD: Given that immune-inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine-related molecules could serve as clinically useful biomarkers of treatment-resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor-α, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy. RESULTS: The serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor-α, was significantly higher in treatment-resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment-resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin-6 receptor level measurement was useful for identification of treatment-resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology-Self Report score (QIDS-SR16 ) as a target variable showed that only serum soluble interleukin-6 receptor level could explain the severity of major depressive disorder. CONCLUSION: Based on these results, we recommend measurement of serum soluble interleukin-6 receptor level to discriminate treatment-resistant major depressive disorder patients. High serum soluble interleukin-6 receptor level is associated with the pathogenesis of treatment-resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans-signaling system in onset of treatment-resistant major depressive disorder.

Troglitazone, a Selective Ligand for PPARγ, Induces Cell-cycle Arrest in Human Oral SCC Cells.

AIM: We attempted to clarify the role of Peroxisome proliferator-activated receptor γ (PPARγ) and its ligand, troglitazone (TRO) on oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: The expression of PPARγ gene was examined in 47 human oral SCC tissues and two human oral SCC cell lines, CA9-22 and HSC-4. The effects of TRO on the growth and cell-cycle progression of human oral SCC cells were examined. RESULTS: PPARγ mRNA was detected in 20 of 47 oral SCC tissues and two human oral SCC cells. TRO significantly suppressed the growth of the cells, but did not induce apoptosis. CA9-22 cells treated with TRO showed an increased fraction in the G1 phase and decreased fractions in the S and G2-M phases. CONCLUSION: TRO did not induce apoptosis in oral SCC cells, but did inhibit the growth of the cells by arresting the cell cycle at G1 phase.

Determination of the origin of oral squamous cell carcinoma by microarray analysis: Squamous epithelium or minor salivary gland?

More than 90% of oral cancers are histopathologically squamous cell carcinomas (SCCs). According to clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or minor salivary glands. Here, we examined whether some oral SCCs originate from minor salivary glands, and investigated whether these tumors show particularly aggressive biological behavior. The mRNA expression profiles of samples obtained from six patients with oral floor SCC (five men, one woman; mean age, 62.7 years) were analyzed using a microarray containing 32,878 probes. The six samples were divided into two groups by clustering of expression levels of 845 probes differentially expressed in normal oral squamous epithelium and normal salivary glands. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these nine marker genes by reverse transcriptase-polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p = 0.044, Chi-square test). Furthermore, SCC derived from minor salivary glands showed a poor event-free survival rate (p = 0.017, Kaplan-Meier analysis). In conclusion, determination of the origin of oral SCC is helpful in planning treatment for patients with oral SCC.

Cost of illness of hepatocellular carcinoma in Japan: A time trend and future projections.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth leading cause of death in Japan. The aim of this study was to calculate the social burden of HCC using the cost of illness (COI) method, and to identify the key factors driving changes in the economic burden of HCC. METHODS: Utilizing government-based statistical nationwide data, the cost of illness (COI) method was used to estimate the COI for 1996, 1999, 2002, 2005, 2008, and 2014 to make predictions for 2017, 2020, 2023, 2026, and 2029. The COI comprised direct and indirect costs (morbidity and mortality costs) of HCC. RESULTS: From 1996 to 2014, COI trended downward. In 2014, COI (579.2 billion JPY) was 0.71 times greater than that in 1996 (816.2 billion JPY). Mortality costs accounted for more than 70% of total COI and were a major contributing factor to the decrease in COI. It was predicted that COI would continue a downward trend until 2029, and that the rate of decline would be similar. CONCLUSIONS: COI of HCC has been decreasing since 1996. Treatment of patients infected with hepatitis C virus using newly introduced technologies has high therapeutic effectiveness, and will affect the future prevalence of HCC. These policies and technologies may accelerate the downward tendency of COI, and the relative economic burden of HCC is likely to continue to decrease.

Cost of illness of leukemia in Japan - Trend analysis and future projections.

BACKGROUND: Leukemia is a deadly hematological malignancy that usually affects all age groups and imposes significant burden on public funds and society. The objective of this study was to analyze the cost of illness (COI) of leukemia, and to mark out the underlying driving factors, in Japan. METHODS: COI method was applied to the data from government statistics. We first summed up the direct and indirect costs from 1996 to 2014; then future COI for the year 2017-2029 was projected. RESULTS: Calculated COI showed an upward trend with a 13% increase from 1996 to 2014 (270-305 billion yen). Increased COI was attributed to an increase in direct costs. Although mortality cost accounted for the largest proportion of COI, but followed a downward trend. Decreased mortality costs reflected the effects of aging. Mortality cost per person also decreased, however, the percentage of mortality cost for individuals ≥65 years of age increased consistently from 1996 to 2014. If a similar trend in health-related indicators continue, COI would remain stable from 2017 to 2029 regardless of models. CONCLUSION: COI of leukemia increased from 1996 to 2014, but was projected to decrease in foreseeable future. With advancement of new therapies, leukemia has become potentially curable and require long-term care; so direct cost and morbidity cost will remain unchanged. This reveal the further continuing burden on public funds. Thus, the information obtained from this study can be regarded as beneficial to future policy making with respect to government policies in Japan.