Tobacco smoke extract induces premature skin aging in mouse.
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Animals↗
Biomedical subjects
Yuko Ono
Publications and source records attributed to Yuko Ono.
Mutational analysis of the BRAF gene in colorectal mucinous carcinoma in association with histological configuration.
Genetic alterations and their association with clinicopathological features in colorectal mucinous carcinoma (MC) remain unknown. In particular, little is known about the mutational status of the BRAF gene, which is activated by oncogenic Ras. This study aimed to evaluate the status of BRAF together with K-ras, p53 and mismatch-repair deficiency to clarify their association with tumorigenesis of colorectal MC. BRAF and K-ras mutations were determined in 43 colorectal MCs by direct sequencing. p53 alteration was investigated immunohistochemically. The status of mismatch-repair deficiency was assessed by microsatellite analyses and immunohistochemistry for hMLH1. We also examined the association between these molecular alterations and clinicopathological features including histological configuration. BRAF mutation was detected in 4 (9.3%) tumors and was located at codon 599 of exon 15 in all cases. K-ras mutation was detected in 13 tumors (30.2%). No BRAF and K-ras mutations were identified simultaneously in the same tumor. The incidence of mismatch-repair deficiency tended to be higher in MC with BRAF mutation than without. In terms of histological configuration, we classified the cases according to growth type by tumor edge morphology. All MCs with BRAF mutation and 9 of 13 MCs (69.2%) with K-ras mutation were classified as polypoid type. BRAF and K-ras mutation did not affect patient prognosis, but non polypoid type was significantly more aggressive than polypoid type. Our findings indicate that BRAF mutation plays an important role in the tumorigenesis of colorectal MC and in tumor edge morphology, similar to K-ras mutation.
Adaptor Proteins, Signal Transducing↗
Autoimmune pancreatitis diagnosed on the basis of immunohistology alone. A case report.
CONTEXT: The differential diagnosis between autoimmune pancreatitis and pancreatic cancer is sometimes difficult, especially for those patients in whom laboratory and radiological criteria are lacking. CASE REPORT: A 72-year-old woman was found to have a tumor in the head of the pancreas. Laboratory data showed no abnormal values, including gammaglobulins or autoantibodies. Endoscopic retrograde cholangiopancreatography showed extrinsic stenosis of the main pancreatic and lower common bile ducts. Computed tomography showed a lesion in the head of the pancreas. With a tentative diagnosis of head of the pancreas cancer, the patient underwent pancreaticoduodenectomy. Macroscopically, a tumor 2 cm in diameter not having clear margins was evident in the head of the pancreas. Histological examination showed the infiltration of lymphocytes, plasma cells, and eosinophils with lymphoid follicles around the main pancreatic duct. Immunohistological examination demonstrated that the main pancreatic duct was surrounded by abundant IgG4-positive plasma cells. CONCLUSIONS: The patient was diagnosed as having autoimmune pancreatitis on the basis of the immunohistological findings alone, without any well-defined criteria such as high serum level of IgG4 and presence of autoantibodies before or after surgery.
Aged↗
Proton magnetic resonance spectroscopy (MRS) of metastatic brain tumors: variations of metabolic profile.
BACKGROUND: Spectroscopic imaging can be helpful for the noninvasive identification of parenchymal brain tumors. The objective of the present study was the characterization of the metabolic profile of intracranial metastases, based on proton magnetic resonance spectroscopy (MRS). METHODS: One hundred and four metastatic brain tumors were evaluated by long-echo (TR, 2000 ms; TE, 136 ms) single-voxel volume-selected proton MRS. In 83 patients the tumor fraction within the MRS voxel constituted more than 50%. RESULTS: Compared to normal brain, the tumors showed statistically significant decreases of N-acetylaspartate (P < 0.0001), creatine (P < 0.0001), and the [NAA]/choline-containing compounds ratio (P < 0.0001), increases of [Cho] (P < 0.0001) and the mobile lipids/[Cr] ratio (P < 0.0001) and the lactate/[Cr] ratio (P < 0.05), and the more frequent presence of [Lip] (P < 0.0001) and [Lac] (P < 0.0001) resonances. However, the majority of these differences were lost when data for patients whose tumor fraction within the MRS voxel constituted less than 50% were analyzed separately. Determination of the predominant metabolite peak on the MR spectrum [NAA, Cho, Lip] permitted us to define three general metabolic patterns of brain metastases, which, showed statistically significant associations with the size of the neoplasm (P < 0.001), type of its contrast enhancement (P < 0.01), and the extent of perilesional edema (P < 0.05). CONCLUSION: Proton MRS can define metabolically different subsets of metastatic brain tumors, and these characteristics should be taken into consideration during the differential diagnosis of parenchymal brain lesions.
Aged↗
P16-immunostaining pattern as a predictive marker of lymph node metastasis and recurrence in early uterine cervical cancer.
OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor.
Biomarkers, Tumor↗
Prediction of colorectal neoplasia by quantitative methylation analysis of estrogen receptor gene in nonneoplastic epithelium from patients with ulcerative colitis.
PURPOSE: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC). Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis. EXPERIMENTAL DESIGN: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and 10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum. The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene. RESULTS: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0% in those without neoplasia (P<0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P<0.001). CONCLUSIONS: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.
Adult↗
Evaluation of tumor cell dissociation as a predictive marker of lymph node metastasis in submucosal invasive colorectal carcinoma.
PURPOSE: Tumor cell dissociation-the histologic finding of small solid carcinoma cell clusters and groups of dissociated dedifferentiated carcinoma cells at the invasive front-is related to tumor metastasis and patient prognosis. However, few previous reports have examined tumor cell dissociation in submucosal invasive colorectal carcinoma. We investigated the relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. We also examined immunohistochemical expression of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. METHODS: Submucosal invasive colorectal carcinoma tissue samples from 20 patients with lymph node metastasis and 100 patients without lymph node metastasis were evaluated. Sections stained with hematoxylin and eosin were evaluated for tumor cell dissociation. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin and beta-catenin. RESULTS: Tumor cell dissociation was more frequently identified in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.0001). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.025). Nuclear expression of beta-catenin tended to be present in submucosal invasive colorectal carcinoma cases with lymph node metastasis (P = 0.063). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with tumor cell dissociation than in those without tumor cell dissociation (P = 0.0023). CONCLUSIONS: Our results suggest that there is a relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. Tumor cell dissociation formation might be related to abnormal expression patterns of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Tumor cell dissociation and decreased membranous expression of E-cadherin would be important predictive markers for lymph node metastasis in submucosal invasive colorectal carcinoma.
Cadherins↗
Malignant stromal tumor, so called "gastrointestinal stromal tumor", with rhabdomyomatous differentiation occurring in the gallbladder.
Gastrointestinal stromal tumors (GISTs) constitute the largest category of primary nonepithelial neoplasms of the gastrointestinal tract. It is extremely rare that this tumor occurs in the bile tract, and only a few cases have been reported. Immunohistochemically, the tumor cells revealed a phenotype similar to Cajal cells, occasionally with differentiation to smooth muscle cells or neural cells. We present a case of malignant stromal tumor similar to GISTs with rhabdomyomatous differentiation of the gallbladder in a 68-year-old woman. The resected tumor was predominantly composed of spindle cells with rhabdomyomatous differentiation. Immunohistochemical study revealed diffuse staining of tumor cells using vimentin despite negative staining for desmin or S-100. This indicated a mesenchymal origin of the cells without smooth muscle or neuronal differentiation. Myoglobin-positive cells, in which phosphotungstic acid hematoxylin staining revealed cross striations of the cytoplasm, suggested rhabdomyomatous differentiation. Diffuse positivity for KIT in the cells suggested that the pathogenesis of this tumor may resemble that of GIST. The tumor may have derived from a mesenchymal stem cell that had undergone partial rhabdomyomatous differentiation.
Aged↗
Tumor cell dissociation score highly correlates with lymph node metastasis in superficial esophageal carcinoma.
BACKGROUND: It is still not clear which parameters are important for predicting the metastatic potential of superficial esophageal squamous cell carcinoma (SESCC). The purpose of the present paper was thus to investigate tumor cell dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis. METHODS: Thirty-three SESCC were classified into four groups based on the depth of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were classified as group A; carcinomas invading to the muscularis mucosa or less than one-third of the upper submucosa were classified as group B; those invading to the middle layer of the submucosa were classified as group C; and those invading one-third of the lower submucosa were classified as group D. The TCD score was calculated by dividing the length of the TCD region by the maximal longitudinal length of the area of invasion into or beyond the lamina propria, and multiplying by 100. E-cadherin expression of the carcinomas was investigated in the TCD area and the successive area of mucosal invasive carcinoma (SAM). RESULTS: The incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in group C and 57.1% in group D. The mean TCD scores (+/-SEM) of SESCC with lymph node metastasis were higher than that without (85.3 +/- 5.7, 16.3 +/- 3.9, respectively; P < 0.001). In group C, the TCD score of cases with lymph node metastases was higher than in those without lymph node metastasis (P < 0.001). E-cadherin expression was significantly reduced in the area of TCD compared with the SAM located over the TCD area (P < 0.001). CONCLUSIONS: The TCD score is an important predictive marker for lymph node metastasis in SESCC. Clinical evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would enable accurate prediction of lymph node metastasis and extend the indication of EMR treatment for SESCC.
Aged↗
Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors.
BACKGROUND AND AIM: Recent advances in colonoscopic techniques have led to the increased detection of, and interest in, superficial type colorectal tumors, and a new category, the 'laterally spreading tumor (LST)', has been proposed. However, the characteristics of the genetic alterations in these LSTs have not yet been fully determined. We therefore classified LSTs as LST-granular (LST-G) or LST-non-granular (LST-NG), according to their macroscopic appearance, and examined the genetic alterations in these two tumor groups compared with those in protruded type tumors. METHODS: We obtained a total of 62 colorectal tumors, including 26 protruded type, 17 LST-G and 19 LST-NG, from specimens resected surgically or endoscopically. We examined K-ras codon 12 mutations by using the polymerase chain reaction-restriction fragment length polymorphism method and by fluorescence direct sequencing. We also performed immunohistochemistry to analyze cyclooxygenase (COX)-2 and gastrin abnormalities. RESULTS: The incidence of K-ras mutation was 50.0% in protruded type tumors, 76.5% in LST-G, and 26.3% in LST-NG. The frequencies of COX-2 overexpression were 73.1, 88.2, and 31.6%, respectively, and those of gastrin overexpression were 61.5, 82.4, and 26.3%, respectively. Therefore, LST-G is similar to protruded type tumors in that the incidence of K-ras mutation and the frequencies of COX-2 and gastrin overexpression are high. LST-NG differs from both of these tumor types in that the values of these three indicators are all low. CONCLUSIONS: These results show that LST-G and LST-NG have different genetic alterations.
Colorectal Neoplasms↗
Endometrial adenosquamous carcinoma with osteoclast-like giant cells: immunohistochemistry and histogenesis.
Primary extraskeletal epithelial neoplasms containing osteoclast-like giant cells (OGCs) are rare. We herein describe a case of adenosquamous carcinoma that developed in the endometrium together with non-neoplastic OGCs. The patient was a 72-year-old woman who underwent radical hysterectomy with salpingo-oophorectomy and lymph node dissection after being diagnosed with uterine cancer. Histologically, the tumor was found to be an adenosquamous carcinoma containing a large number of OGCs and mononuclear cells (MNCs) that had infiltrated into the stroma. Immunohistochemically, the OGCs and MNCs stained strongly positive for KP-1 and alpha-1-antichymotrypsin, and negative for the epithelial markers epithelial membrane antigen (EMA) and cytokeratins. These findings suggest that the OGCs and MNCs in this patient's tumor originated from monocytes/histiocytes, and most likely developed as part of the stromal reaction to the neoplasm.
Adenocarcinoma↗
Histopathological study of small (<2 cm) gastric carcinoma with signet-ring cell component: significance of the admixed glandular components.
Admixture of signet-ring cell carcinoma component (SIG) and glandular component (GC) is sometimes found in a gastric cancer. The aim of this study was to elucidate the biological behavior of the gastric cancer containing either SIG only (SIG-type tumor) or SIG admixed with GC (SIG-GC-type tumor). Forty-three cases of SIG-type tumor and 26 cases of SIG-GC-type tumor, less than 2 cm in largest diameter, were examined. Twenty-six cases (60%) of SIGs were less than 10 mm in size, whereas only 3 cases (12%) of SIG-GCs were less than 10 mm in size (p<0.0001). Submucosal invasion by cancer cells was found in 12 cases of SIG-GCs but was not found in any of the SIGs. Those SIG-GCs showed gastric phenotype. It is important to note SIG-GC-type tumor for histopathological diagnosis.
Adenocarcinoma↗
Subdural hyperintense band on diffusion-weighted imaging of chronic subdural hematoma indicates bleeding from the outer membrane.
The diffusion-weighted magnetic resonance (MR) imaging characteristics of chronic subdural hematoma and the correlation between hematoma liquidity and apparent diffusion coefficient (ADC) were investigated in 26 consecutive patients, 16 males and 10 females aged 42 to 92 years (mean +/- SD 73.3 +/- 13.1 years), with 31 chronic subdural hematomas. The chronic subdural hematomas were divided into homogeneous, separate, and trabecular types based on diffusion-weighted MR imaging findings. Almost all hematomas were low intensity on diffusion-weighted imaging, and the mean ADC value was 1.81 +/- 0.79 x 10(-3) mm2/sec. The high intensity areas in the subdural hematomas consisted of several types: high intensity line along the dura mater (subdural hyperintense band), high intensity along the intrahematoma septum, and laminar shape along the inner membrane. The subdural hyperintense bands accounted for almost all high intensity areas in the subdural hematomas. The mean ADC value of the high intensity areas was 0.76 +/- 0.24 x 10(-3) mm2/sec, close to that of the normal brain. The subdural hyperintense bands were considered to be intracellular and/or extracellular methemoglobin based on the T1- and T2-weighted imaging and intraoperative findings. The subdural hyperintense band is an important finding indicating relatively fresh bleeding from the outer membrane. Diffusion-weighted imaging shows liquid subdural hematoma as low intensity, and measurement of the ADC values can differentiate between liquid and solid components of the chronic subdural hematoma.
Adult↗
Diffusion-weighted imaging of traumatic subdural hematoma in the subacute stage.
Five cases of traumatic subdural hematomas in the subacute stage (from 7 to 20 days after head injury) were treated in one male and four females, aged from 63 to 82 years, with evacuation via craniotomy in three and aspiration via burr hole surgery in two. All hematomas were evaluated by T1-, T2-, and diffusion-weighted magnetic resonance imaging, and measurement of the apparent diffusion coefficient (ADC). Diffusion-weighted imaging showed the hematoma as a crescent high intensity area with a low intensity rim close to the brain surface (two-layered structure) in four cases and as high intensity with low intensity components in one case. The high intensity areas under the dura mater on diffusion-weighted imaging appeared as homogeneous high intensity on T1- and T2-weighted imaging in four cases, and inhomogeneous high intensity on T1- and isointensity on T2-weighted imaging in one case. The mean ADC value of the high intensity areas was 0.58 +/- 0.23 (mean +/- standard deviation) x 10(-3) mm2/sec. The operative findings revealed the high intensity areas as solid clots. The low intensity areas on diffusion-weighted imaging appeared as homogeneous high intensity in four cases and inhomogeneous isointensity with high intensity components in one case on T1- and T2-weighted imaging. The mean ADC value of the low intensity areas was 2.03 +/- 0.27 x 10(-3) mm2/sec. The operative findings revealed the low intensity areas as mixtures of resolved clot and cerebrospinal fluid. Diffusion-weighted imaging showed the characteristic two-layered structure in traumatic subdural hematomas in the subacute stage, and analysis of the ADC values was useful for differentiating solid from liquid hematoma and for selection of the surgical procedure.
Aged↗
Spectroscopy and navigation.
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Algorithms↗
Gamma knife surgery for choroidal neovascularization in age-related macular degeneration. Technical note.
The authors conducted a study to determine a way of overcoming the poor-quality demonstration of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) on conventional magnetic resonance (MR) imaging studies. The poor MR imaging demonstration of CNV in patients with AMD makes the use of gamma knife surgery more difficult. This difficulty, however, can be overcome by use of a modified time-of-flight MR imaging,sequence with Gd enhancement and coronal reconstruction.
Age Factors↗
Prognostic significance of CD83 positive, mature dendritic cells in the gallbladder carcinoma.
Dendritic cells (DCs) are very potent antigen-presenting cells that play an essential role in the primary immune response to carcinoma. Tumor-infiltrating DCs have been found to be clinically significant in many human malignancies such as colon, stomach, lung, breast and hepatic carcinoma. However, clinical significance of activated and/or immature DCs in gallbladder carcinoma has not been reported yet. Thus, we immunohistochemically evaluated CD83+ DCs and CD1a+ DCs of cancerous and peritumoral area in 29 cases of resected gallbladder. In the results, CD83(+) DCs were significantly fewer in cancerous area than that in peritumoral area (1.55/hpf vs. 4.26/hpf, p=0.0047), but the numbers of CD1a(+) DCs did not differ (p=0.075). In addition, we defined a CD83 index as CD83(+) DCs/(CD83(+) DCs plus CD1a(+) DCs), and analyzed the relationship between CD83 index and clinicopathological factors. The group with a higher CD83 index (index >0.316) showed significantly better prognosis than the group with a lower CD83 index (index < or =0.316) in cancerous and peritumoral areas. In conclusion, we suggest the importance of tumor-infiltrating CD83(+) DCs as a useful prognostic factor for patients with gallbladder carcinoma.
Antigens, CD↗
[Clinical and electroencephalogram study of 5 children with hypothalamic hamartoma].
We retrospectively studied 5 children with hypothalamic hamartoma (HH) to elucidate the clinical, neuroimaging and electroencephalogram (EEG) characteristics of this disorder. In all cases, high resolution MRI scans demonstrated an intrahypothalamic mass protruding into the 3rd ventricle. An initial symptom was epileptic attack in 4 cases and precocious puberty in the remaining one. Gelastic seizures developed in 4 of 5 patients at ranging from 2 days to 11 years of age. The ictal EEGs during the gelastic seizures showed diffuse attenuation of background activity, followed by rhythmic slow discharges either diffusely or in the central area. Gamma-knife radiosurgery was performed on 2 cases whose seizures were resistant to available antiepileptic drugs. One of the 2 patients was responded significantly to this treatment, showing the disappearance of combined attacks and a marked reduction of the generalized spike-waves discharges. A more aggressive therapy, including gamma-knife radiosurgery and surgical treatment, should be considered for patients whose seizures are resistant to the medical treatment and causing deterioration of intelligence and behavioral problem.
Adolescent↗