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The accurate diagnosis of vascular anomalies (VAs) is considered a challenging endeavor. Misdiagnosis of VAs can lead clinicians in the wrong direction, such as the performance of an unnecessary biopsy or inappropriate surgical procedures, which can potentially lead to unforeseen consequences and increase the risk of patient injury. The purpose of the present study was to develop an approach for the diagnosis of VAs of the oral and maxillofacial region based on computed tomography (CT), magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI (DCE-MRI). In the present study, the CT and MR images of 87 VAs were examined, and the following imaging features were evaluated: Detectability of the lesion, the periphery of the lesion, the inner nature of the lesion, the density of the lesion on CT, the signal intensity of the lesion on MRI, the detectability of phleboliths and the shape of the lesion. A total of 29 lesions were further evaluated using the contrast index (CI) curves created from the DCE-MRI images. A diagnostic diagram, which is based on the imaging features of VAs and CI curve patterns, was subsequently extrapolated. The results obtained demonstrated that the VAs were detected more readily by MRI compared with CT, whereas the detectability of phleboliths was superior when using CT compared with MRI. VAs showed a propensity for homogeneous isodensity on CT, whereas, by contrast, they exhibited a propensity for heterogeneous hyperdensity on CE-CT. VAs also showed a propensity for homogeneous intermediate signal intensity when performing T1-weighted imaging (T1WI), heterogeneous high signal intensity when performing short tau inversion recovery MRI, and heterogeneous high signal intensity when performing fat-saturated CE-T1WI. The CI curves of VAs were found to exhibit a specific pattern: Of the 29 CI curves, 23 (79.3%) showed early weak enhancement, followed by a plateau leading up to 400-600 sec. An imaging-based diagnostic diagram was ultimately formulated. This diagram can act as an aid for radiologists when they are expecting to find a VA, and hopefully serve the purpose of simplifying the diagnostic process. Taken together, the findings of the present study indicated that DCE-MRI may be considered a useful tool for the diagnosis of VAs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Al-Hammad et al.)

Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) are highly promising therapies for oral squamous cell carcinoma (OSCC). The assessment of PD-L1 expression may help predicting the therapeutic effect of ICIs and, thus, benefit patient selection. Contrast index (CI) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been proven as efficient to assess microvessel density (MVD) in OSCC. The present study aimed to determine the correlation between DCE-MRI parameters and MVD and between DCE-MRI parameters and PD-L1 expression to determine whether DCE-MRI could be used non-invasively to evaluate PD-L1 expression in patients with OSCC. A total of 21 patients with primary OSCC who had undergone a 3T MRI scan, including DCE-MRI, were included in the present study, and CI curve-derived parameters were examined. The MVD and PD-L1 expression in the surgically resected specimens were analyzed using immunohistochemistry (IHC) staining for CD31 and IHC staining for PD-L1, respectively. The results demonstrated that the expression levels of these markers were correlated with DCE-MRI parameters. PD-L1 expression levels were found to be significantly correlated with the maximum CI (CI-max; P=0.007), peak CI (CI-peak; P=0.007), maximum CI gain (CI-gain; P=0.006) and MVD (P=0.001) values. The mean CI-max, CI-peak, CI-gain and MVD values were significantly higher in tumors with high PD-L1 expression (P<0.05). MVD levels were also significantly correlated with the time of CI-max (T-max; P=0.003) and CI-gain (P=0.037). The mean CI-gain was significantly increased, and the mean T-max was significantly shorter in high MVD tumors (P<0.05 and P<0.01, respectively). In summary, the findings from the present study confirmed the correlation between CI parameters, derived from DCE-MRI, and MVD, and suggested that these parameters may be correlated with PD-L1 expression in OSCC tumor cells., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tekiki et al.)

The purpose of this study was to evaluate computed tomography (CT) findings of radicular cysts with a focus on location, size, and condition of the surrounding bone. Subjects comprised 60 men and 86 women (mean age 47.2 years) with histopathologically confirmed radicular cysts who underwent CT examination between 2012 and 2014. Mesiodistal and buccolingual diameters were measured at the location where the lesion appeared to be largest on CT axial images. Of the 146 cases, 103 lesions were in the maxilla and 43 were in the mandible. Mesiodistal diameter of the maxillary lesions was significantly larger than that of the mandibular lesions. However, the ratio of mesiodistal diameter to buccolingual diameter in the mandible was significantly larger than that in the maxilla. Bone expansion was more significant in the maxilla than in the mandible. Mesiodistal and buccolingual diameters in only the maxilla and perilesional sclerotic radiolucency in images of both jaws were significantly associated with the severity of clinical symptoms. The findings suggest that radicular cysts in the maxilla are accompanied by bone expansion in the mesiodistal and buccolingual directions and those in the mandible progress in the mesiodistal direction without bone expansion. Clinical acute symptoms (pain and swelling) are correlated with lesion size in the maxilla; such a correlation is not clear for mandibular lesions, and discovery of mandibular lesions may, therefore, be delayed.

Purpose: The prevalence of supernumerary teeth has been reported to be between 0.1% and 3.8%. The aim of this study was to determine the prevalence, clinical significance, and associated pathologies of fourth molars based on a retrospective study and a literature review., Materials and Methods: A 5-year retrospective prevalence study was conducted at the Department of Oral Diagnosis and Dentomaxillofacial Radiology of Okayama University Hospital, Okayama, Japan. The study involved extracting data from the digital records of patients from January 1, 2013 through December 31, 2017. The sampling frame included all patients who had panoramic radiographs, cone-beam computed tomography (CT), and multislice CT images during the period under review., Results: A total of 26,721 cases were reviewed and 87 fourth molars were identified. The prevalence of fourth molars in the 5-year study at Okayama was calculated as 0.32%. The mean age of patients with a fourth molar was 30.43 years, and the male-to-female ratio was 1:0.98. The vast majority of cases were in the maxilla (92%) and had normal shapes (89.7%); furthermore, 82.8% of cases were unerupted., Conclusion: The prevalence of fourth molars in the study population was found to be 0.32%, and fourth molars occurred with approximately equal frequency in males and females. Fourth molars were more common in the maxilla and were predominantly unerupted and small.

Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations. The OSCC-EGFR-EVs were then able to enter into and transform epithelial cells leading to increased mesenchymal traits with increased vimentin and spindle-like shapes. EGF priming of OSCC cells further increased this EMT-initiating effect of the OSCC-EVs. The internalization and pro-EMT effects of the OSCC-EVs were largely blocked by cetuximab. Thus, OSCC-derived EVs transform normal epithelial cells into a mesenchymal phenotype and anti-EGFR therapeutic antibody cetuximab inhibits such a carcinogenic effect of the OSCC-EVs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The ATP-binding cassette transporter G1 (ABCG1) is a cholesterol lipid efflux pump whose role in tumor growth has been largely unknown. Our transcriptomics revealed that ABCG1 was powerfully expressed in rapidly metastatic, aggregative colon cancer cells, in all the ABC transporter family members. Coincidently, genetic amplification of ABCG1 is found in 10-35% of clinical samples of metastatic cancer cases. Expression of ABCG1 was further elevated in three-dimensional tumoroids (tumor organoids) within stemness-enhancing tumor milieu, whereas depletion of ABCG1 lowered cellular aggregation and tumoroid growth in vitro as well as hypoxia-inducible factor 1α in cancer cells around the central necrotic areas in tumors in vivo . Notably, depletion of ABCG1 triggered the intracellular accumulation of extracellular vesicles (EVs) and regression of tumoroids. Collectively, these data suggest that ABCG1 plays a crucial role in tumorigenesis in metastatic cancer and that depletion of ABCG1 triggers tumor regression with the accumulation of EVs and their derivatives and cargos, implicating a novel ABCG1-targeting therapeutic strategy by which redundant and toxic substances may be accumulated in tumors leading to their regression.

Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Adenoid cystic carcinoma (ACC) is a slowly growing malignant neoplasm with a propensity for perineural invasion. Microscopic invasion of ACC often prevents its detection on computed tomography (CT) or magnetic resonance imaging (MRI). We herein report a rare case of sublingual ACC presenting as a "skip lesion" that rapidly infiltrated the mandible after tumor resection. A 64-year-old man presented to Okayama University Hospital with an 18-month history of swelling in the right floor of the mouth. Clinical examination displayed an ulcerated swollen mass in that region. An enhanced mass was detected in the right sublingual space on CT and MRI. Bone surface erosion was observed at the inferior border of the mandible, but continuity with the sublingual mass or mass around that lesion was not detected by imaging. Sublingual tumor resection and selective neck dissection were performed by the pull-through method. Histopathologically, the surgical margins were free of cancer cells, and the tumor was diagnosed as ACC. Continuity with the sublingual mass and mandibular bone was not detected intraoperatively. However, marked bone resorption was detected in the anterior mandible 3 months after the operation. Biopsy was performed, and the findings indicated the same histological type of sublingual ACC. This case suggests that a malignant tumor close to the jaw bone requires the clinician to consider the possibility of bone invasion and to observe a wide region surrounding the tumor using imaging examination.

The usefulness of dental approaches, such as oral management, has gained recognition among patients treated for head and neck cancer. In particular, oral management plays a very important role before, during, and after treatment in patients undergoing radiotherapy, chemotherapy, or a combination of both. However, specialized dentistry knowledge and techniques that are useful for patients undergoing radiotherapy for head and neck cancer have yet to be reported. Therefore, in this review article, our aim is to introduce dental approaches in radiotherapy for patients with head and neck cancer that have been developed and are currently being used at our institute.

Salivary gland carcinomas are rare tumors, representing ~0.5% of all malignancies. Myoepithelioma is also uncommon, representing ~1% of all salivary gland tumors. Myoepithelial carcinoma (MC) is even rarer, representing 0.2 to 0.6% of all salivary gland tumors. We herein report a case of MC with multiple metastases arising from a submandibular gland in a 71-year-old male patient and present the associated imaging findings. The patient was considered to have a de novo type of myoepithelial carcinoma, which is reportedly associated with higher malignancy than the transformation type of the disease (i.e., a malignant change from pleomorphic adenoma or myoepithelioma). This was reflected in the multiple lung and bone metastases sites and strong positivity for p53 and Ki-67.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare type of odontogenic carcinoma arising from the jawbone. Odontogenic cysts are true cysts that arise from the dental epithelium, which is associated with tooth formation. The epithelial lining of odontogenic cysts has the potential to transform into various types of odontogenic tumor; however, this transformation from an odontogenic cyst to a malignant tumor is rare. The definitive diagnosis for PIOSCC generally requires the observation of either features of squamous cell carcinoma (SCC) within the jawbone that are distinct from direct invasion from the surface oral epithelium, or evidence of SCC arising from odontogenic epithelium and from tumors that have metastasized to the jawbone from distant sites. In the present study, a case of PIOSCC of the maxilla is presented, which, based on the results of computed tomography and the clinical course, was hypothesized to have originated from an infected residual cyst.

The aim of this study was to create a new phantom for a 3 Tesla (3T) magnetic resonance imaging (MRI) device for the calculation of the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI), and to mimic the ADC values of normal and tumor tissues at various temperatures, including the physiological body temperature of 37°C. The phantom was produced using several concentrations of sucrose from 0 to 1.2 M, and the DWI was performed using various phantom temperatures. The accurate ADC values were calculated using the DWIs of the phantoms, and an empirical formula was developed to calculate the ADC values of the phantoms from an arbitrary sucrose concentration and arbitrary phantom temperature. The empirical formula was able to produce ADC values ranging between 0.33 and 3.02×10 -3 mm 2 /sec, which covered the range of ADC values of the human body that have been measured clinically by 3T MRI in previous studies. The phantom and empirical formula developed in this study may be available to mimic the ADC values of the clinical human lesion by 3T MRI.

Objectives: To evaluate the diagnostic value of MRI for odontogenic tumours., Materials and Methods: 51 patients with odontogenic tumours were subjected to pre-operative MRI examinations. For tumours with liquid components, i.e. ameloblastomas and keratocystic odontogenic tumours (KCOTs), the signal intensity (SI) uniformity of their cystic components (UΣ) was calculated and then their UΣ values were compared. For tumours with solid components that had been examined using dynamic contrast-enhanced MRI (DCE-MRI), their CImax (maximum contrast index), Tmax (the time when CImax occurred), CIpeak (CImax × 0.90), Tpeak (the time when CIpeak occurred) and CI300 (i.e. the CI observed at 300 s after contrast medium injection) values were determined from CI curves. We then classified the odontogenic tumours according to their DCE-MRI parameters., Results: Significant differences between the UΣ values of the ameloblastomas and KCOT were observed on T1 weighted images, T2 weighted images and short TI inversion recovery images. Depending on their DCE-MRI parameters, we classified the odontogenic tumours into the following five types: Type A, CIpeak > 2.0 and Tpeak < 200 s; Type B, CIpeak < 2.0 and Tpeak < 200 s; Type C, CI300 > 2.0 and Tmax < 600 s; Type D, CI300 > 2.0 and Tmax > 600 s; Type E, CI300 < 2.0 and Tmax > 600 s., Conclusion: Cystic component SI uniformity was found to be useful for differentiating between ameloblastomas and KCOT. However, the DCE-MRI parameters of odontogenic tumours, except for odontogenic fibromas and odontogenic myxomas, contributed little to their differential diagnosis.

Objective: The purpose of this study was to explore the 3-dimensional (3D) accuracy of magnetic resonance imaging (MRI) on cone-beam computed tomography (CBCT) images after the registration of MRI images on CBCT images., Materials and Methods: Three Japanese adult females volunteered for this study. To transform digital imaging and communication in medicine (DICOM) data derived from MRI and CBCT images into polygon data, five software programs were used. CBCT and MRI images were obtained within one week, and both were registered by the iterative closest point (ICP) method. To assess the accuracy of the composite MRI-CBCT, the measurement errors of the MRI-CBCT were verified Measurement values were compared using frontal and cephalometric soft-tissue landmarks. Differences were analyzed using the non-parametric Mann-Whitney U test., Results: There were no significant linear measurement errors (P > 0.05) when the images were measured from the superimposed MRI-CBCT images., Conclusion: The MRI images attained from MRI - CBCT registration showed accurate 3D linear measurements.

The purpose of this study was to reveal the relationship between chewing-side preference and anterior disc displacement (ADD) of the TMJ. Thirty-two healthy subjects with ages ranging from 26 to 34 years were selected from volunteer students at the Okayama University Dental School. Subjects were asked to chew freely with two kinds of test foods, beef jerky (hard food) and chiffon cake (soft food), thus expecting different amounts of mechanical loading on the TMJ. One, 4, and 7 s after starting the mastication, subjects were asked to open their mouth momentarily to have a digital image of their mouth taken. The bolus placement area was measured by processing the digital images, calculated as the number of pixel of bolus area. Area asymmetry index was used for the determination of preferred chewing side (PCS). Oblique sagittal MRI scanning in the closed mouth position was taken to evaluate the articular disc position. In asymptomatic subjects with ADD, a significant predominance of the PCS on the ipsilateral side of ADD was observed during the mastication of hard food. On the contrary, no correlation was found between unilateral ADD and PCS for the soft food. From the results of this study, it is suggested that ADD is the associating factor of PCS for hard food. Therefore, it would be necessary to break down the concept of PCS into at least two categories, one for hard food and one for soft food, considering the mechanical loading on the TMJ., (© 2010 Blackwell Publishing Ltd.)

Objectives: To examine oral and maxillofacial lesions other than those related to the chief complaint in panoramic radiographs taken at the department of paediatric dentistry at our hospital., Methods: We retrospectively reviewed all 1092 patients who had visited the department of paediatric dentistry at our hospital and had a panoramic radiograph taken between August 1999 and October 2004. The following information was obtained from the patients' files and panoramic radiographs: gender, age, chief complaints and the presence or absence of lesions., Results: Lesions were observed in 140 of the 1092 panoramic radiographs (12.8%). Among the 140 patients discovered to have lesions in the panoramic radiographs, 66 (47.1%, or 6.05% of the entire group of 1092 patients) had different lesions from those underlying the chief complaint. These 66 patients ages ranged from 3 years to 14 years and the lesions involved 39 (59.1%) missing teeth, 20 (30.3%) mesiodentes, 4 supernumerary teeth, 1 odontoma, 1 radicular cyst and 1 impacted tooth. The missing teeth were observed in the central and lateral incisor, canine, and first and second premolar positions of both jaws, especially in the lower lateral incisor and upper central incisor positions., Conclusions: We were able to detect incidental lesions at a rate of 6.05% (66 of 1092 patients) and at a relatively early age (mean 6.8 years) in the present study. Early treatment of these lesions could avoid maxillofacial deformity and other complications.

Objectives: To examine mesiodens with regard to their status, their influence on adjacent teeth and their alteration during the follow-up period., Methods: From retrospective reviews of all patients who visited our institution from 1990-2001, we identified 200 patients (256 mesiodentes) who were shown to have mesiodentes on the basis of a periapical radiograph, a panoramic radiograph or an axial radiograph., Results: The number of supernumerary teeth was one in 146 cases (73%), two in 52 cases (26%) and three in 2 cases (1%). Of 256 mesiodentes, the direction of the crown of the mesiodens was inverted in 172 (67%), in a normal direction in 69 (27%) and in a horizontal direction with regard to the tooth axis in 15 (6%). Of the 147 mesiodentes for which axial radiography was performed, 131 (89%) were located at a palatal site against the dental arch, 16 (11%) overlapped the dental arch and none were at a labial site. Of our 200 cases, a delay of eruption of the permanent central incisor was seen in 12 (6%), malposition or rotation of the central incisor in 5 (2.5%) and dentigerous cyst formation arising from mesiodens in 22 (11%). Marked movement of the mesiodens was seen in 10 cases during the follow-up period of 5-7 years. Some complication arising from mesiodens was seen in 19.5% of all cases in our research., Conclusion: Although mesiodentes are not caused by malocclusion, they may cause it. A long period of impaction of mesiodentes may bring about dentigerous cyst formation or movement of the mesiodentes.

We present a new method of fenestration and continuous pressure as a simple, effective and uninvasive procedure for the treatment of plunging ranulas. We have recently used in four female patients, aged 10-29 years old. After treatment, the patients remained symptom-free and assessment by magnetic resonance imaging (MRI) showed regression of the ranula in all cases. The procedure resulted in satisfactory healing and we advocate it as a simple and effective treatment that is better for patients than conventional treatment.

We investigated the relationship between the enhanced patterns acquired by dynamic MRI and the tumor cell proliferation estimated by immunostaining proliferating cell nuclear antigen (PCNA) in oral squamous cell carcinoma (SCC). Thirty patients with primary oral SCC underwent dynamic contrast enhanced (DCE)-MRI using a three-dimensional fast imaging with steady-state precession sequence. Tumor cell proliferation of all surgical specimens was evaluated using immunohistochemical staining with the anti-PCNA antibody. The relationship between the dynamic MRI parameters (maximum CI and maximum CI gain) and the PCNA labeling index was statistically analyzed using regression analysis. The time contrast index curves of all cases showed a rapid and high uptake pattern. The PCNA labeling index showed a significant correlation with maximum CI and maximum CI gain (P<0.0001, r=0.866 and P=0.0019, r=0.544, respectively). The assessment of DCE-MRI parameters may provide valuable information for tumor cell proliferation of the patients with oral cancer.

Objective: Odontoma is a comparatively common odontogenic tumor, and it may lead to interference with the eruption of its associated tooth. Odontomas are mostly associated with permanent teeth, and they are rarely associated with deciduous teeth. The purpose of this report is to analyze 107 odontomas and to present a case of complex odontoma associated with a lower deciduous second molar., Subject and Methods: The 106 cases were analyzed with regard to the following parameters: age, gender, location, erupted teeth, congenital missing teeth, radiological features, histopathological features and prognosis., Results: Of the 106 cases, 41 were complex odontoma, 62 were compound odontoma, and three were immature odontoma. Compound odontoma had a predilection for the anterior. Complex odontoma occurred more often at the mandible., Conclusion: Odontoma located above the tooth crown of lower deciduous molar did not behave clinically different from that associated with permanent tooth. An odontoma could be related with a supernumerary tooth or a missing tooth. If odontomas, which interfered with tooth eruption, were extirpated early, the impacted teeth would probably erupt normally and be normal in shape.

Cepharanthin (Ce) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The results of our previous in vitro study indicated that Ce reduces thermotolerance by enhancing thermosensitivity. In the present study, we investigated the in vitro and in vivo effects of Ce on thermosensitivity and thermotolerance using a murine mammary carcinoma, MCa, and C3H/HeN mice. Ce enhanced the thermosensitivity of MCa cells for heating at 44 degrees C not only in vitro but also in vivo. The in vivo enhancement ratio +/- SD of Ce at 100 mg/kg for heating at 44 degrees C was 1.3+/-0.3. The fractionated heat treatments at 44 degrees C for 30 and 60 min with an interval time of 0-6 days resulted in the development of remarkable thermotolerance and the expression of heat shock protein 70 in MCa tumors after the first heating. Ce at 100 mg/kg given immediately after the first heating increased the expression of heat shock protein 70 in MCa tumors, and did not reduce the development of thermotolerance. Ce given immediately before the first or second heating also did not inhibit the thermotolerance. The results of this study suggest that Ce enhances the thermosensitivity of MCa tumors as a thermosensitizer, but that this mild thermosensitizing property of Ce might be insufficient to conquer the remarkable thermotolerance in MCa tumors that develops after the first heating.

Intracellular accumulation of adriamycin (ADR) has been reported to be influenced by cell membrane potential. We first evaluated intracellular accumulation of ADR and 3,3'-(di-n-hexyl)-2,2'-oxacarbocyanine iodide (NK-2280), an indicator of cell membrane potential, and found a good correlation between ADR and NK-2280 intracellular accumulation in several cell lines. This suggests that ADR accumulation may be influenced by cell membrane potential or the mechanisms of NK-2280 accumulation may be similar to those of ADR accumulation. Next, we observed the influence of the NA+/H+ exchanger and Cl-/HCO3- exchanger on the intracellular accumulation of ADR and NK-2280, and found that ADR accumulation decreased with increasing concentrations of 3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide (amiloride), an inhibitor of the Na+/H+ exchanger, and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl-/HCO3- exchanger, however, NK-2280 accumulation was increased by amiloride, and decreased by DIDS. The increased accumulation of NK-2280 induced by amiloride may be due to the increased cell membrane potential caused by the inhibition of H+ ion efflux and NA+ ion influx due to the inhibition of the Na+/H+ exchanger. The decreased accumulation of NK-2280 may be also due to the decreased cell membrane potential caused by the inhibition of Cl- ion efflux due to the inhibition of the Cl-/HCO3- exchanger by DIDS. However, the decreased rate caused by DIDS was greater than the increased rate caused by amiloride. Therefore, it is suggested that the decreased accumulation of NK-2280 by DIDS may be influenced by other factors apart from cell membrane potential. These results suggest that the Cl-/HCO3- exchanger may be related to both ADR accumulation, and NK-2280 accumulation, and that the Na+/H+ exchanger may be related to ADR accumulation, but not NK-2280. This suggests that the Cl-/HCO3- exchanger is of low selectivity.