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Biomedical subjects

K Inai

Publications and source records attributed to K Inai.

At least 37 records · Page 2Linked to original sources

Evaluation of p53 gene mutation and loss of heterozygosity of 3p, 9p and 17p in precancerous lesions of 29 lung cancer patients.

To assess the multiple steps involved in carcinogenesis we evaluated p53 gene mutation frequencies, and loss of heterozygosity (LOH) of chromosomes 3p, 9p and 17p in hyperplasia, squamous metaplasia, dysplasia, squamous cell carcinoma in-situ and early squamous cell carcinoma of the bronchial epithelium, using immunohistochemical, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and microsatellite analysis. Overexpression of p53 oncoprotein was observed in 31% of mild dysplasia, 50% of moderate and 67% of severe dysplasia. Mutation of the p53 gene, however, was confirmed only in 2 severe dysplasias. LOH of 3p, 9p and 17p were detected in 8% of mild and 6% of moderate dysplasias. Among other types of bronchial lesions, two columnar cell hyperplasias showed LOH of 3p and 17p, respectively. These results suggest that LOH of 3p or 9p may be a rare but early event in the development of squamous cell carcinoma of the lung. In particular, deletion of 3p21.3 is a relatively common event in premalignancy. The results also suggest that p53 gene abnormalities occur during the following stage of carcinogenesis.

Base Sequence↗

Clinicocytopathological and immunohistochemical study of adenoma malignum of the uterine cervix.

Adenoma malignum is a rare type of very highly differentiated adenocarcinoma of the uterine cervix, and is quite difficult to diagnose because there are few findings definitely suggesting malignancy on cytologic or histologic examination. We recently encountered four patients with adenoma malignum and reviewed their clinicocytopathological and immunohistochemical findings. The most characteristic symptom was a watery discharge and an enlarged cervix was palpable, while multiple cystic lesions (MCL) were observed by transvaginal and abdominal ultrasonography, CT or MRI. On cytodiagnosis, the cervical gland cells formed large sheets or showed a palisading arrangement. Slightly enlarged nuclei and yellowish-orange staining of the cytoplasmic mucus were the characteristic findings. On histological examination, many cervical glands of different sizes were present and extended deep into the muscle layer, while branching or papillary growth into the lumen was also observed. On immunohistochemical study, HIK1083, a monoclonal antibody for gastric gland mucous cell mucin, was found to be positive in 3 of 4 cases, and this was fairly useful in the diagnosis of adenoma malignum.

Adenocarcinoma↗

Numerous conglomerate inclusions in slowly progressive familial amyotrophic lateral sclerosis with posterior column involvement.

A 59-year-old woman with slow progression of the loss of motor function and predominant lower motor manifestation during a 14-year period showed familial amyotrophic lateral sclerosis (fALS) with posterior column involvement, neuropathologically. Conglomerate inclusions (CIs) were observed in the remaining neurons in various areas, including the spinal anterior horn, posterior horn, Clark's column, accessory cuneate nucleus, tegmental reticular formation, motor nucleus of the trigeminal nerve, nucleus of the facial nerve, hypoglossal nucleus, medial nucleus of the thalamus, dentate nucleus, and motor cortex (Betz cells). Immunohistochemically, it was newly identified that the CIs showed marked immunoreactions with antibodies to phosphorylated and non-phosphorylated neurofilaments and to 64, 120, and 200 kD neurofilaments. The CIs were partially immunoreactive with the anti-ubiquitin antibody, although they reacted only weakly (or not at all) with anti-Cu/Zn superoxide dismutase (SOD1) antibody. Ultrastructurally, the CIs were comprised of neurofilaments. These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.

Amyotrophic Lateral Sclerosis↗

Tubular seminoma of the testis.

A case of tubular seminoma in a 33-year-old man is reported. The tumor occurred in his right testis, measuring 7 x 6 x 6 cm in size. Microscopically, most of the tumor cells were arranged in solid or hollow tubular patterns. The tumor cells had round nuclei with vesicular chromatin and clear or granular cytoplasm, characteristic features of seminoma cells. A classic seminoma component and intratubular atypical germ cells occupying approximately 5% of the tumor area were noted. Immunohistochemical staining revealed that the tumor cells were diffusely placental alkaline phosphatase and vimentin positive, and focally cytokeratin positive. These findings are consistent with a tubular seminoma. The differential diagnoses are discussed.

Adult↗

Idiopathic granulomatous meningoencephalitis presenting as an intracranial tumor.

A 2-year-old girl presented with a single episode of generalized seizure. Magnetic resonance imaging examination showed an intracranial mass with a diameter of 2.5 cm in the right parieto-occipital region of the cerebrum. These clinicoradiological findings were suggestive of intracranial tumor. Histologically, fibroblastic proliferation of storiform pattern was noted, associated with epithelioid granulomas. The etiological pathogens for the granulomas could not be detected even though investigation of special histochemical staining, immunohistochemical study and DNA analysis of Mycobacterium tuberculosis by polymerase chain reaction technique was performed. On electron microscopic examination, the area appearing as a storiform pattern consisted of fibroblasts showing much dilated rough endoplasmic reticulum and slender tappering cytoplasmic processes without cellular junctional complex. No organisms were identified in the granulomatous area of the lesion. From those findings the diagnosis as idiopathic granulomatous meningoencephalitis was made.

Biomarkers↗

Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma.

KAI1, a metastasis suppressor gene of prostate cancer, is located on human chromosome 11p11.2. Down-regulation of KAI1 mRNA during tumor progression and metastasis has been reported for several kinds of cancer, but the mechanism of this down-regulation is not known. In the present study, our aim was to ascertain the relationship between down-regulation of KAI1 mRNA expression and KAI1 gene alterations in lung cancer. Forty-nine cases of adenocarcinoma of the lung were studied by reverse-transcriptase polymerase chain reaction (RT-PCR) assay of KAI1 mRNA and by immunohistochemical detection of KAI1 protein. In addition, markers of the microsatellite loci D11S1344 and D11S1326 were used to investigate loss of heterozygosity (LOH) and replication errors (RERs) of the KAI1 gene region. The RT-PCR assay showed that there was no correlation between KAI1 mRNA expression and either the age of the patients or tumor size. By contrast, KAI1 mRNA expression was significantly correlated with gender (P=0.047), metastasis to the lymph nodes or other organs (P=0.004), the histological grade of the tumor (P=0.036) and the pathological stage (P=0.049). Immunohistochemical staining showed that in one case without metastasis, loss of KAI1 mRNA was associated with invasion of the stroma by KAI1 protein-negative cancer cells. The numbers of informative cases by microsatellite analysis were 14 (28.6%) of 49 at D11S1344 and 27 (55.1%) of 49 at D11S1326; none of 49 adenocarcinomas showed LOH or RERs at these loci. These results suggest that down-regulation of KAI1 mRNA expression rarely if ever involves LOH or RERs of the KAI1 gene region in primary lung adenocarcinoma.

Adenocarcinoma↗

High incidence of meningioma among Hiroshima atomic bomb survivors.

Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10(5) persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.

Brain↗

Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion.

STUDY OBJECTIVE: We assessed the usefulness of endobronchial ultrasonography in the determination of the depth of tumor invasion of the tracheobronchial wall. METHODS: We performed a needle-puncture experiment on normal tissue of 45 specimens to determine the laminar structure of the tracheobronchial wall. In addition, we compared the ultrasonographic determinations of tumor invasion from 24 lung cancer cases with the histopathologic findings. RESULTS: The cartilaginous portions of the extrapulmonary bronchi and the intrapulmonary bronchi exhibited a five-layer structure. Starting on the luminal side, the first layer (hyperechoic) was a marginal echo, the second layer (hypoechoic) was the submucosal tissue, the third layer (hyperechoic) was the marginal echo on the inner side of the bronchial cartilage, the fourth layer (hypoechoic) was bronchial cartilage, and the fifth layer (hyperechoic) was the marginal echo on the outer side of the cartilage. In the membranous portions, the first layer (hyperechoic) was a marginal echo, the second layer (hypoechoic) was smooth muscle, and the third layer (hyperechoic) corresponded to the adventitia. Comparisons between the ultrasonograms and the histopathologic findings in 24 lung cancer cases revealed that depth diagnosis was the same in 23 lesions (95.8%) and was different in 1 lesion (4.2%). In the single case in which the findings were different, lymphocytic infiltration that protruded between the cartilage rings was mistakenly interpreted as tumor infiltration. CONCLUSIONS: This method allows visualization of the laminar structure of the tracheobronchial wall, which is impossible with other diagnostic imaging methods.

Bronchi↗

Symptomatic Rathke's cleft cyst coexisting with central diabetes insipidus and hypophysitis: case report.

We describe a 48-year-old female with acute onset of central diabetes insipidus followed by mild anterior pituitary dysfunction. Magnetic resonance imaging (MRI) revealed enlargement of the hypophysis-infundibulum accompanied by a cystic component. She underwent a transsphenoidal exploration of the sella turcica. Histological examination showed foreign body type xanthogranulomatous inflammation in the neurohypophysis which might have been caused by rupture of a Rathke's cleft cyst. The MRI abnormalities and anterior pituitary dysfunction improved after a short course of corticosteroid administration, but the diabetes insipidus persisted. The histological findings in this case indicated the site of RCC rupture and the direction of the progression of RCC induced neurohypophysitis and adenohypophysitis.

Cysts↗

Hepatic tumor rupture following effectual treatment with irinotecan in a patient with highly refractory malignant lymphoma.

We describe a patient with highly refractory malignant lymphoma who died of hepatic tumor rupture following treatment with irinotecan (CPT-11). This 60-year-old man with non-Hodgkin's lymphoma (diffuse large B-cell lymphoma) demonstrated disease recurrence in the liver and the vertebrae following high-dose chemotherapy and autologous hematopoietic stem cell transfusion. He was treated with CPT-11 at a dose of one third of the conventional dose used for non-Hodgkin's lymphoma in Japan. The tumor in the liver markedly decreased in size but then ruptured. Although pathologic hepatic tumor rupture is a rare complication in patients with malignant lymphoma of the liver, this case demonstrates that hepatic tumor rupture may occur in refractory malignant lymphomas that reveal extensive degradation by this new, effective salvage therapy.

Antineoplastic Agents, Phytogenic↗

Loss of CD9 with Expression of CD31 and VEGF in Breast Carcinoma, as Predictive Factors of Lymph Node Metastasis.

Immunohistochemical staining for CD9, CD31 and vascular endothelial growth factor(VEGF)was performed in breast carcinoma specimens. CD9 was expressed in the membrane of carcinoma cells in 61 of 93 cases(67%), CD31 in the membrane of carcinoma cells in 23 of 86 cases(27%), and VEGF in the cytoplasm of carcinoma cellsin 26 of 86 cases(30%). The expression of CD9, CD31 and VEGF did not singly correlate with any clinicopathological factors. However, a loss of CD9 with concurrent expression of CD31 or VEGF in the invasive component showed a slight correlation with lymph node metastasis. These findings suggest that the potential for metastatic spread to lymph nodes in breast carcinoma may be synergically affectedby various factors.

Journal Article↗

Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin.

We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.

Antineoplastic Agents↗

p21WAF1/CIP1 expression in primary lung adenocarcinomas: heterogeneous expression in tumor tissues and correlation with p53 expression and proliferative activities.

p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, discovered to be a downstream effector of p53-dependent cell cycle regulation. In order to elucidate the significance of p21 expression in lung adenocarcinomas, we performed immunohistochemical analysis of p21, p53 and Ki-67 expression in surgically resected lung adenocarcinomas. In non-neoplastic tissue, a few bronchial and bronchiolar suprabasal and ciliated cells, and a few type II alveolar cells and alveolar macrophages in the peripheral lung, were p21 positive, but the positive rate in normal lung tissue was very low (<1%). All 91 lung adenocarcinomas examined showed p21 immunoreactivity: 39 cases (42.9%) and 52 cases (57.1%) showed high and low p21 expression levels, respectively. There was no significant correlation between p21 expression and p53 expression, the loss of heterozygosity status of the p53 gene, histological grade determined by the predominant histology, lymph node metastasis, pathological stage, tumor size, smoking history or gender. A positive, not inverse, correlation between p21 and Ki-67 expression was observed. We also observed heterogeneous expression of p21 in lung adenocarcinomas, i.e. in about two-thirds of the tumors, the tumor cells in the peripheral regions were p21 positive more frequently than were those in the central regions. More intense p21 expression tended to occur in the more highly differentiated areas. These results suggest that p21 is involved in tumor cell differentiation and the physiological mechanism that protects against tumor extension.

Adenocarcinoma↗

Angiomyofibroblastoma of the vulva: a mitotically active variant?

A case of angiomyofibroblastoma in a 48-year-old woman is reported. The tumor occurred as a left vulval mass and was treated by simple excision. It was located in the subcutaneous tissue of the left vulva and was well circumscribed, measuring 2.8 x 2.7 x 2.5 cm. Microscopically, the tumor was composed of hypocellular and cellular areas with well-developed small vessels. Spindle or polygonal cells were arranged with perivascular accentuation in an edematous or fibrocollagenous background. Some spindle-shaped or polygonal stromal cells were also arranged in epithelioid nests. In some areas, mitoses were frequent (maximum 3/10 high-power field). Immunohistochemically, the stromal cells were positive for vimentin and desmin, but negative for alpha-smooth muscle actin, S-100, neurofilament, estrogen receptor, progesterone receptor, CD31 and CD34. The average labeling index of Ki-67 in stromal cells was 3.1%. Ultrastructural analysis demonstrated that the stromal cells adhered with primitive junctions and contained intermediate filaments with no focal density in the cytoplasm. These findings were consistent with angiomyofibroblastoma, although previously reported cases did not show so many mitoses. Therefore, this case was suggested to be a mitotically active variant.

Angiofibroma↗

Proliferative activity, p53 expression and loss of heterozygosity on 3p, 9p and 17p in atypical adenomatous hyperplasia of the lung.

We examined the preneoplastic nature of atypical adenomatous hyperplasia (AAH) of the lung by comparing the proliferative activity, p53 oncosuppressor gene product and loss of heterozygosity (LOH) on 3p, 9p and 17p of 20 AAH lesions (8 cases) with corresponding normal peripheral lung tissue and adenocarcinoma from the same cases. Analysis of proliferative activity with the Ki-67 labelling index and argyrophilic nucleolar organizer regions (AgNORs) score indicated that AAH had a proliferative activity intermediate between that of normal cell and adenocarcinoma. Although low level expression of p53 was detected in 7 AAH lesions, the intensity of p53 expression in AAH was weaker than that in carcinomas. Microsatellite analysis of chromosome 3p, 9p and 17p showed LOH of 18%, 13% and 6% respectively in the AAH lesions, while the corresponding carcinomatous lesions showed LOH of 67%, 50% and 17% respectively. All AAH lesions that showed LOH had moderate or severe histological atypia. One AAH lesion with moderate atypia showed LOH both on 3p and 17p. In conclusion, these results indicated that AAH lesions with moderate or severe atypia may show the preneoplastic stage of lung adenocarcinoma.

Adenocarcinoma↗