Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage.

BACKGROUND: Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1. METHODS: We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1. RESULTS: Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression. CONCLUSIONS: The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions.

Nodal-based radiomics analysis for identifying cervical lymph node metastasis at levels I and II in patients with oral squamous cell carcinoma using contrast-enhanced computed tomography.

OBJECTIVE: Discriminating metastatic from benign cervical lymph nodes (LNs) in oral squamous cell carcinoma (OSCC) patients using pretreatment computed tomography (CT) has been controversial. This study aimed to investigate whether CT-based texture analysis with machine learning can accurately identify cervical lymph node metastasis in OSCC patients. METHODS: Twenty-three patients (with 201 cervical LNs [150 benign, 51 metastatic] at levels I-V) who underwent preoperative contrast-enhanced CT and subsequent cervical neck dissection were enrolled. Histopathologically proven LNs were randomly divided into the training cohort (70%; n = 141, at levels I-V) and validation cohort (30%; n = 60, at level I/II). Twenty-five texture features and the nodal size of targeted LNs were analyzed on the CT scans. The nodal-based sensitivities, specificities, diagnostic accuracy rates, and the area under the curves (AUCs) of the receiver operating characteristic curves of combined features using a support vector machine (SVM) at levels I/II, I, and II were evaluated and compared with two radiologists and a dentist (readers). RESULTS: In the validation cohort, the AUCs (0.820 at level I/II, 0.820 at level I, and 0.930 at level II, respectively) of the radiomics approach were superior to three readers (0.798-0.816, 0.773-0.798, and 0.825-0.865, respectively). The best models were more specific at levels I/II and I and accurate at each level than each of the readers (p < .05). CONCLUSIONS: Machine learning-based analysis with contrast-enhanced CT can be used to noninvasively differentiate between benign and metastatic cervical LNs in OSCC patients. KEY POINTS: • The best algorithm in the validation cohort can noninvasively differentiate between benign and metastatic cervical LNs at levels I/II, I, and II. • The AUCs of the model at each level were superior to those of multireaders. • Significant differences in the specificities at level I/II and I and diagnostic accuracy rates at each level between the model and multireaders were found.

Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma.

BACKGROUND: Our aim was to investigate the disease-free survival in patients with tongue squamous cell carcinoma receiving metronomic neoadjuvant chemotherapy with 5-fluorouracil prodrugs (UFT or S-1) plus bleomycin compared with those who had up-front surgery retrospectively. METHODS: In this retrospective study, 108 patients with stages I to II tongue squamous cell carcinoma who had undergone surgery were divided into the "surgery group" or "neoadjuvant chemotherapy group." RESULTS: A total of 41 patients received up-front surgery; 67 received metronomic neoadjuvant chemotherapy with UFT plus bleomycin (39) or S-1 plus bleomycin (28). The rate of disease-free survival was the primary outcome measure. Neoadjuvant 5-fluorouracil prodrugs did not correlate higher with improved disease-free survival than up-front surgery (72 and 54%, respectively; hazard ratio for recurrence or death, 0.54; 95% confidence interval [CI], 0.28 to 1.03; P = 0.06). Patients who received S-1 were more likely than those who received UFT to have pathological complete response (46% vs. 15%; P = 0.007). Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery (79% vs. 54%; hazard ratio, 0.41; 95% CI, 0.15 to 0.98; P = 0.04). However, neoadjuvant UFT did not improve disease-free survival as compared with up-front surgery (67% vs. 54%, respectively; hazard ratio, 0.66; 95% CI, 0.31 to 1.33; P = 0.24). CONCLUSIONS: Neoadjuvant S-1 chemotherapy, as compared with up-front surgery, significantly improved disease-free survival among patients with tongue squamous cell carcinoma. CLINICAL RELEVANCE: A choice of drugs before neoadjuvant metronomic chemotherapy is needed.

Synchronous quadruple multiple primary cancers of the tongue, bilateral breasts, and kidney in a female patient with a disease-free survival time of more than 5 years: a case report.

BACKGROUND: Reports of synchronous multiple primary cancers in patients with oral cancer have recently been increasing because of progress in radiographic diagnostic techniques. Multiple primary cancers in patients with oral cavity cancer mainly occur in the head and neck region, lung, and esophagus. 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is usually used to identify synchronous multiple primary cancers. CASE PRESENTATION: We herein describe a 69-year-old woman diagnosed with synchronous quadruple multiple primary cancers, namely a squamous cell carcinoma of the mobile tongue, invasive ductal carcinoma of the right breast, intraductal carcinoma of the left breast, and chromophobe renal cell carcinoma of the right kidney. We removed the four tumors over three surgical procedures to reduce the surgical risk because the patient had diabetes mellitus. To the best of our knowledge, this combination of multiple primary cancers has not been reported to date. Importantly, we followed this case for 5 years after surgery. The patient was alive and well with no clinical or radiologic signs of recurrent or metastatic disease at the time of this writing. CONCLUSIONS: In the present case, the kidney cancer could not be detected by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography but could be detected by contrast-enhanced computed tomography. To avoid overlooking multiple primary cancers of the kidney, we suggest that contrast-enhanced computed tomography should cover a region extending to the inferior margin of the kidney, rather than only to the liver, in patients with oral cavity cancer.

Mixed tumour of the skin of the lower lip: A case report and review of the literature.

Mixed tumour of the skin or chondroid syringoma (CS) is a rare and mostly benign neoplasm of the sweat glands. Although CS is frequently located on varied parts of the head and neck region, the lower lip is a rarely reported site. The present report describes a case of CS of the lower lip in a 58-year-old male as an expository case to further emphasise the need for proper diagnosis, appropriate treatment and prognostic evaluation. The patient presented with a round, non-tender, slightly hard and mobile mass beneath the mucocutaneous junction of his left lateral side of the lower lip. Radiology revealed a mass measuring 11x11x7 mm3 in size at a depth of ~2 mm. Furthermore, magnetic resonance T1- and T2-weighted images showed slightly low and high signal intensities, respectively. A provisional diagnosis of benign tumour of the lower lip was made, and surgical excision biopsy taken under local anaesthesia, while considering the patient's cosmetic appearance. Histopathology demonstrated features akin to apocrine gland, chondroid and myxoid stroma consistent with the diagnosis of benign CS. No evidence of recurrence or satellites were recorded after a follow-up of nearly 2 years. Although rare, a high index of suspicion for CS among other cutaneous adnexal tumours of the lower lip is necessary. In addition, interprofessional collaboration in the management of such oral tumours could enhance patient satisfaction amid prevailing intraoral and aesthetic concerns.

Mucoepidermoid carcinoma of the anterior lingual salivary gland: A rare case report.

Mucoepidermoid carcinomas (MECs) are rare head and neck malignant tumours that were originally considered to be benign. It has been estimated that ~20% of MECs in the major salivary glands, such as the parotid gland, and 50% in the several minor salivary glands found in the oral cavity, are malignant. The diagnosis of MECs is mainly based on ancillary and immunohistochemistry testing. However, owing to the difficulty in harvesting adequate material for histological examination, the histopathological diagnosis of intraoral MECs may be particularly challenging. We herein report a rare case of an 82-year-old patient who presented to the Department of Oral and Maxillofacial Surgery of Ryukyu University Hospital with complaints of a progressive swelling and pain in the ventral surface of the apex of the tongue. The patient had previously undergone needle biopsy and the histopathological analysis of the tumour suggested a diagnosis of irritation fibroma. To ensure a more accurate histopathological assessment, an incisional biopsy was performed, in addition to the haematological and radiological assessments. Examination of the obtained surgical specimen confirmed low-grade MEC of the anterior lingual gland. The tumour was surgically excised, the patient healed uneventfully and no recurrence was detected on the regular 3-year follow-up. Although MECs are relatively more common in the minor salivary glands of the oral cavity, they are a rare occurrence in the anterior lingual gland. Therefore, adequate histological material should be surgically harvested to perform a complete evaluation of the morphology and cytology of the tumour and ensure the accuracy of diagnosis.

Deep Learning for the Preoperative Diagnosis of Metastatic Cervical Lymph Nodes on Contrast-Enhanced Computed ToMography in Patients with Oral Squamous Cell Carcinoma.

We investigated the value of deep learning (DL) in differentiating between benign and metastatic cervical lymph nodes (LNs) using pretreatment contrast-enhanced computed tomography (CT). This retrospective study analyzed 86 metastatic and 234 benign (non-metastatic) cervical LNs at levels I-V in 39 patients with oral squamous cell carcinoma (OSCC) who underwent preoperative CT and neck dissection. LNs were randomly divided into training (70%), validation (10%), and test (20%) sets. For the validation and test sets, cervical LNs at levels I-II were evaluated. Convolutional neural network analysis was performed using Xception architecture. Two radiologists evaluated the possibility of metastasis to cervical LNs using a 4-point scale. The area under the curve of the DL model and the radiologists' assessments were calculated and compared at levels I-II, I, and II. In the test set, the area under the curves at levels I-II (0.898) and II (0.967) were significantly higher than those of each reader (both, p < 0.05). DL analysis of pretreatment contrast-enhanced CT can help classify cervical LNs in patients with OSCC with better diagnostic performance than radiologists' assessments alone. DL may be a valuable diagnostic tool for differentiating between benign and metastatic cervical LNs.

Patterns of recurrence after low-dose postoperative radiotherapy for head and neck squamous cell carcinoma.

BACKGROUND: Postoperative chemoradiotherapy is recommended for patients with head and neck squamous cell carcinoma with positive margins or extracapsular extension at high risk of recurrence. However, high-dose radiotherapy in the head and neck region often causes severe acute and late radiation-related adversities. In our institution, the radiation dose has been relatively lower than that used in Western countries to reduce radiation-related toxicities. Therefore, in this study, we examined the treatment outcomes of low-dose postoperative chemoradiotherapy. METHODS: The outcomes of 90 consecutive head and neck squamous cell carcinoma patients who received postoperative radiotherapy between June 2009 and December 2016 were retrospectively analyzed. All patients received postoperative three-dimensional conformal radiotherapy with or without concurrent systemic chemotherapy. The median patient age was 65 years. Concurrent chemoradiotherapy was administered at a total dose of 50.4 Gy in 28 fractions (daily fraction, 1.8 Gy). High-risk patients received 10.8 Gy of boost irradiation in six fractions. For radiotherapy alone, the irradiation dose was up to 54 Gy in 30 fractions and 64.8 Gy in 36 fractions for high-risk patients to increase the treatment intensity. RESULTS: The median follow-up period was 40.5 months. The 3-year locoregional control and overall survival rates were 67.5% and 82.7%, respectively. A significantly higher proportion of patients with oral cavity carcinoma experienced locoregional failure (p = 0.004). The acute adverse events were mild, and the only late adverse event was grade 3 dysphagia (n = 3). CONCLUSION: This study suggests that de-escalation of the postoperative radiation dose can potentially reduce the severe adverse events of irradiation in patients while ensuring its effectiveness. In patients with oral cavity carcinoma, it might be necessary to increase the radiation dose.

A case of oral cancer with preoperative transcatheter aortic valve implantation for aortic stenosis: A case report.

Aortic valve stenosis [or aortic stenosis, (AS)] is a risk factor in non-cardiac surgery. Guidelines from the European Heart Association recommended that AS treatment should be applied prior to non-cardiac surgery. Transcatheter aortic valve implantation (TAVI) is a method of minimally invasive AS treatment. The present study reports a case of tongue excision and neck dissection after TAVI for a patient with tongue cancer and AS. A 79-year-old woman was diagnosed with AS following preoperative examination for tongue cancer. The patient was judged as a high-risk case for open-heart surgery after consultation with staff at the University Hospital of The Ryukyus. It was concluded that TAVI should be performed prior to cancer surgery. On day 21 following TAVI, cancer surgery was performed and the patient was discharged from hospital 22 days after tongue cancer surgery. To the best of our knowledge, there is no report of oral cancer surgery after TAVI. TAVI is generally used as a short-term treatment strategy for AS associated with head and neck cancer due to its minimally invasive nature. In the present case, oral cancer surgery was performed closely following TAVI without serious complications. The case demonstrated that TAVI might be useful for severe AS patients with high surgical risk prior to cancer resection surgery. However, further cases are required to confirm the safety and effectiveness of TAVI treatment strategies.

miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A).

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. Therefore, novel therapeutic options are needed to improve prognosis of OSCC. Recently, microRNAs (miRs) have received increasing attention as a potential therapeutic tool for carcinomas. However, no definitive miR-based drugs for patients with OSCC have been reported to date. The aim of this study was to identify new miRs potentially involved in cellular processes associated with OSCC malignancy, which could lead to novel therapeutic strategies. MATERIALS AND METHODS: We identified miRs that are modulated in OSCC and possibly regulate OSCC malignancy, using miR microarray on OSCC cell lines. RESULTS: miR-935 and miR-509-3p were down-regulated in OSCC cell lines and patient tissues. When miR-935 was overexpressed in HSC-3-M3 cells, proliferation, migration, and invasion of the cell line was suppressed, whereas apoptosis was increased. Moreover, we showed that the gene inositol polyphosphate-4-phosphatase type I A (INPP4A) is a potential target whose expression is positively regulated by miR-935. CONCLUSION: miR-935 may function as a tumor suppressor by inhibiting OSCC malignancy via INPP4A induction. Therefore, miR-935 can be a new therapeutic candidate for OSCC treatment.

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi's Sarcoma.

Currently, Kaposi's sarcoma (KS) is treated following the recommendations of international guidelines. These guidelines recommend esophagogastroduodenoscopy/colonoscopy for detecting multicentric KS of visceral lesions. Second primary malignancies (SPMs) are also a common KS complication; however, information on their detection and treatment is unfortunately not yet indicated in these guidelines. This paper reports on an 86-year-old man who suffered from quadruple primary malignancies: skin classic KS with colon adenocarcinoma, oral squamous cell carcinoma (maxilla), and well-differentiated stomach adenocarcinoma. Gastric cancer was incidentally detected during esophagogastroduodenoscopy, which was performed to detect visceral KS. We suggest that esophagogastroduodenoscopy/colonoscopy be routinely performed during the follow-up of patients with KS. As SPMs are crucial complications in patients with KS, these malignancies should be detected as early as possible.

Regulation of chemokine production via oxidative pathway in HeLa cells.

Inflammation is associated with disease progression and, by largely unknown mechanisms, has been said to drive oncogenesis. At inflamed sites, neutrophils deploy a potent antimicrobial arsenal that includes proteinases, antimicrobial peptides, and ROS. Reactive oxygen species (ROSs) induce chemokines. In the present study, the concentrations of IL-8 in culture supernatants of HeLa cells treated with ROS were determined by enzyme-linked immunosorbent assay. We used o-phenanthroline to deplete Fe(2+) in order to investigate the mechanisms through which ROSs induce IL-8 secretion in our system. The iron chelator o-phenanthroline effectively inhibited H(2)O(2)-induced ERK2 activation. Enzyme-linked immunosorbent assays showed that IL-8 protein secretion was elevated in ROS-treated HeLa cells. When Fe(2+) was removed from these cells, IL-8 secretion was inhibited. Collectively, these results indicate that Fe(2+)-mediated Erk pathway activation is an important signal transduction pathway in ROS-induced IL-8 secretion in epithelial cells.

Oral health behavior of children and guardians' beliefs about children's dental caries in Vientiane, Lao People's Democratic Republic (Lao PDR).

Dental caries is considered a major health problem among schoolchildren in Lao People's Democratic Republic (Lao PDR). According to Health Belief Model (HBM)-based research, children's oral health behavior can be determined by their guardians' beliefs. This study aimed to describe children's oral health behavior and its association with childhood dental caries, as well as to assess associations between children's tooth-brushing behavior and guardians' beliefs in an urban area of Lao PDR, using HBM. Data were collected from ten primary schools in the Sisattanak district, the Vientiane capital, between 2013 and 2014. Ten dentists with the help of dental hygienists and schoolteachers conducted dental health check-ups at the schools that diagnosed dental caries based on visual inspection. They also conducted a questionnaire-based survey with the schoolchildren's guardians to collect data including socio-economic and demographic information, their children's oral health behavior, and guardians' beliefs derived from HBM, including perceived susceptibility to and perceived severity of child dental caries, perceived benefit of and perceived barrier to child's tooth brushing, and self-efficacy in making their children brush their teeth twice daily. A mixed-effects logistic regression model assessed the association between dental caries and children's oral health behavior and between children's tooth-brushing behavior and guardians' beliefs. Data from 1161 of 1304 (89.0%) children registered at the schools were used. The prevalence of dental caries was 82%. Children who brushed their teeth ≥ twice/day were significantly less likely to have dental caries than those brushing once or seldom (OR: 0.64, 95% CI: 0.45 to 0.91). The number of children who brushed twice daily also significantly increased with the increased level of guardians' self-efficacy (OR: 2.14, 95% CI: 1.91 to 2.41). In conclusion, childhood dental caries was associated with daily tooth brushing. Children's tooth-brushing behavior was associated with guardians' self-efficacy in making their children brush twice daily.

Thymoma appearing 9 years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review.

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

Targeting EphA4 abrogates intrinsic resistance to chemotherapy in well-differentiated cervical cancer cell line.

Alkylating reagent chemotherapy for human cancers is not curative, and relapse occurs due to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD cells after chemotherapy, a phenomenon referred to as intrinsic resistance, depends on reactive oxygen species. Well-differentiated regions of the tumor are intrinsically resistant to chemotherapy. Receptor tyrosine kinase erythropoietin-producing human hepatocellular receptor A4 (EphA4) protein is highly expressed in the well-differentiated tumor-derived cervical cancer cell line Caski, but not in poorly differentiated tumor-derived cervical cancer cell lines such as HeLa or SiHa. Here, we report that reactive oxygen species produced by cisplatin exposure induce tyrosine phosphorylation of EphA4. After observing that EphA4 is activated by cisplatin, we rationalized a combination chemotherapy that induces well-differentiated cervical cancer death. Pharmacological inhibition of EphA4 increased cisplatin-induced cell death in Caski cells. Moreover, we observed increased expression levels of the senescence marker cyclin-dependent kinase inhibitor 2A (p16) in the absence of EphA4 kinase function after stimulation of Caski cells with cisplatin exposure. Mechanistically, cisplatin induces chemotherapy resistance of Caski cells by upregulating Lyn, a Src family kinase (SFK) that interacts with EphA4, through a pathway involving reactive oxygen species. Thus, the reactive oxygen species-SFK-EphA4 axis presents new potential drug targets for chemotherapy resistance.

Dedifferentiated liposarcoma of the oral floor: A case study and literature review of 50 cases of head and neck neoplasm.

Dedifferentiated liposarcoma (DDLS) has a relatively poor prognosis, however this neoplasm rarely occurs in the head and neck. To date, no definite protocol has been established for the diagnosis and treatment of head and neck DDLS. The present study reports the case of a 69-year-old male patient with DDLS of the oral floor. To the best of our knowledge, this is the first documented case of oral floor DDLS. In addition, this is the first reported case with the development of a second primary malignancy following the treatment of head and neck DDLS. A literature review of 50 cases of head and neck DDLS revealed that preoperative biopsy is not reliable for the diagnosis of these tumors and an accurate pathological diagnosis with total resection is preferred.

Triple primary cancer of the head and neck, skin and prostate: A case report and literature review.

Second primary cancer (SPC) is an important prognostic factor for patients with head and neck cancer (HNC); therefore, the association between the prognosis and development of SPC has been well-reported. The use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is valuable to examine cancer stage, evaluate treatment responses and investigate suspected relapses or metastases. In the present study, the case of a male patient who was diagnosed with three primary cancer types, including well to moderately differentiated squamous cell carcinoma (SCC) of the mandible, axillary cutaneous poorly differentiated SCC and prostate adenocarcinoma, was described. Among these, mandible cancer was the first diagnosed when the patient was 70 years of age. Synchronous skin and prostate cancer (PRC) types then developed 3 years later. To the best of our knowledge, this is the first report of the aforementioned combination of cancer types. Postoperative FDG-PET was not performed as no lesions of recurrence or metastases of mandible cancer were found. Three years later, the PRC was asymptomatic and was incidentally detected by FDG-PET performed for a preoperative evaluation of skin cancer. It was indicated that FDG-PET could be utilized in patients with HNC due to there being no accurate FDG-PET protocol to detect SPC over a long-term follow-up.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma.

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2-ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=-0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and 'delayed LNM' in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR-196a-5p can serve as a therapeutic marker for preventing metastasis.

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography: A case report.

Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

Inhibition of IgE-mediated phosphorylation of FcepsilonRIgamma protein by antiallergic drugs in rat basophilic leukemia (RBL-2H3) cells: a novel action of antiallergic drugs.

We examined the effect of antiallergic drugs, azelastine and epinastine, on the expression of FcepsilonRIalpha, beta, and gamma chains and phosphorylation of the gamma chains in rat basophilic leukemia (RBL-2H3) cells. The cells were cultured for 24 h with IgE treatment in the presence of azelastine or epinastine at the concentration of 10(-5) M. The FcepsilonRIalpha mRNA expression was determined by northern blot analysis. The protein level of FcepsilonRI expressed on the plasma membrane was examined following IgE treatment by immunoprecipitation with anti-IgE light chain, followed by western blot analysis with anti-gamma chain of FcR. Azelastine and epinastine had no effect on the FcepsilonRIalpha, beta and gamma mRNA levels. Although the amount of gamma chain assembled into IgE-bound FcepsilonRI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of gamma chains of IgE-bound FcepsilonRI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of FcepsilonRIgamma protein is not due to their inhibition of mRNA and protein expression, but due to abrogating phosphorylation of the gamma chains, which is important for initiation of FcepsilonRI signaling cascade elicited by IgE interaction.