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Biomedical subjects

H Yokomise

Publications and source records attributed to H Yokomise.

At least 19 recordsLinked to original sources

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT.

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.

Adult↗

MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.

Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (P<0.0001). MRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (P<0.0001). However, no difference was observed in the expression of Arp2, Arp3 or other WASPs. A neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (P<0.0001), and reversed the morphological effects of MRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

Actin-Related Protein 2↗

The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways.

Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.

Carcinoma, Non-Small-Cell Lung↗

[Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the lung; report of a case].

An 80-year-old man was admitted to our hospital because a routine chest X-ray had revealed a nodular shadow in the right lower lung field. Transbronchial lung biopsy (TBLB) failed to give at definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Rapid intraoperative pathological examination diagnosed the tumor as large cell carcinoma. However, bloody pleural effusion was classified as class V. It was judged difficult to perform a curative operation, so the operation was interrupted. Pathological diagnosis was combined large cell neuroendocrine carcinoma and squamous cell carcinoma. Pleurodesis was done, and the patient is under observation at 7 months after the operation.

Aged, 80 and over↗

Clinical application of biological markers for treatments of resectable non-small-cell lung cancers.

We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II-III NSCLCs. In patients with stage II-III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.

Adult↗

The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients.

Immunohistochemical analyses of the effects of hepatocyte growth factor (HGF) and c-Met expression on tumour growth and angiogenesis were performed on 88 patients with non-small-cell lung cancers (NSCLCs). In all, 22 carcinomas (25.0%) were intratumoral HGF-positive, 14 carcinomas (15.9%) were stromal HGF-positive, and 36 carcinomas (40.9%) were intratumoral c-Met-positive. None of the carcinomas were stromal c-Met-positive. Examination of tumour growth revealed that the frequency of tumours with a high Ki-67 index was significantly greater for stromal HGF-positive tumours than for stromal HGF-negative tumours (P=0.0197). The frequency of tumours with a high Ki-67 index was also significantly greater for intratumoral c-Met-positive tumours than for intratumoral c-Met-negative tumours (P=0.0301). However, there was no significant difference in tumour vascularity with relation to intratumoral HGF status, stromal HGF status, and intratumoral c-Met status. The survival rate of patients with intratumoral c-Met-positive tumours was significantly lower than for patients with c-Met-negative tumours (P=0.0095). Furthermore, the survival rate of patients with both intratumoral c-Met-positive and stromal HGF-positive tumours was significantly lower than for patients with either positive tumours, and that of patients with both negative tumours (P=0.0183 and P=0.0011, respectively). A univariate analysis revealed that intratumoral c-Met expression was a significant prognostic factor of NSCLC patients (relative risk=2.642, P=0.0029). The present study demonstrates that tumour-stromal interaction between tumour cell-derived c-Met and stromal cell-derived HGF affects tumour growth and the prognosis of NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗

Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients.

An immunohistochemical analysis for E(epithelial)-cadherin and N(neural)-cadherin expression in relation to tumour angiogenesis was performed in 150 patients with nonsmall cell lung cancer (NSCLC). In all, 71 carcinomas (47.3%) were E-cadherin-negative. Epithelial-cadherin-negative tumours had lymph node metastases significantly more frequently than E-cadherin-positive tumours (P=0.0100). On the other hand, 46 carcinomas (30.7%) were N-cadherin-positive. Regarding tumour vascularity, there was no significant correlation between E-cadherin expression and tumour vascular. In contrast, the frequency of hypervascular tumours was significantly higher for N-cadherin-positive carcinomas than for N-cadherin-negative carcinomas (P=0.0373). Regarding prognosis, the 5-year survival rate of patients with E-cadherin-negative NSCLCs was significantly lower than that of patients with E-cadherin-positive NSCLCs (P=0.0146). In contrast, of the patients with large cell carcinomas, the 5-year survival rate of patients with N-cadherin-positive tumours was significantly lower than that of patients with N-cadherin-negative tumours (P=0.0013). A multivariate analysis demonstrated that E-cadherin status (P=0.0339) and tumour vascularity (P=0.0295) were significant indicators for survival. In conclusion, E-cadherin expression and tumour vascularity are significant prognostic factors of NSCLC patients. Furthermore, N-cadherin expression is associated with tumour angiogenesis, and its expression is one of prognostic factors of patients with large cell carcinomas. Thus, N-cadherin also might play a specific role in undifferentiated large cell carcinomas.

Antigens, CD34↗

The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in nonsmall cell lung carcinoma patients.

BACKGROUND: Angiogenesis has important effects on tumor growth and metastasis. It is regulated by a variety of angiogenic and angiostatic factors. METHODS: To evaluate the effects of tumor cell-derived angiogenic factors, we performed an immunohistochemic study to evaluate the intratumoral expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in relation to intratumoral microvessel density (IMD) in tumors from 104 nonsmall cell lung carcinoma (NSCLC)patients. RESULTS: Fifty-four carcinomas were VEGF-positive, 47 carcinomas were IL-8-positive, and 53 carcinomas were hypervascular tumors. There was no significant correlation between the percentages of positive VEGF-staining and positive IL-8-staining in NSCLCs (rho = 0.174, P = 0.080). The IMD of VEGF-positive carcinomas was significantly greater than that of VEGF-negative carcinomas (P = 0.023). In addition, the IMD of IL-8-positive carcinomas was significantly greater than that of IL-8-negative carcinomas (P =0.013). The overall survival rate of patients with hypervascular tumors was significantly lower than that of patients with hypovascular tumors (41.0% versus 67.0%, P = 0.004). Cox proportional-hazards regression model also demonstrated that angiogenesis was one of the significant factors in predicting the survival of NSCLC patients (relative risk = 1.944, P = 0.041). CONCLUSIONS: Intratumoral expression of VEGF and IL-8 was associated with angiogenesis in NSCLCs. Tumor angiogenesis significantly affected the prognosis of NSCLC patients.

Adult↗

Malignant adenomyoepithelioma of the breast with lung metastases: report of a case.

Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86-year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases.

Aged↗

Spontaneous rupture of a parathyroid adenoma presenting as a massive cervical hemorrhage: report of a case.

We report an unusual case of spontaneous rupture of a parathyroid adenoma causing cervical hemorrhage. A 60-year-old woman presented to our hospital after the sudden development of extensive ecchymosis of her neck and upper anterior chest wall. Computed tomography (CT) scanning revealed a hematoma in the left retrotracheal space, and laboratory examinations revealed significant hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone. Primary hyperparathyroidism was diagnosed, but it was not until the hematoma had subsided, 4 months after her initial presentation, that a parathyroid adenoma was revealed by CT. An operation was performed, and a parathyroid adenoma with hemosiderin deposition was histologically diagnosed. Although this phenomenon is unusual, all endocrine surgeons should be well aware of the possibility of its occurrence.

Adenoma↗

E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer.

BACKGROUND: E-Cadherin plays a major role in maintaining the intercellular junctions in epithelial tissues. The reduction of E-cadherin expression in cancer cells may be associated with tumor differentiation, metastasis, and a poor prognosis. METHODS: Immunohistochemistry for E-cadherin expression was performed on 109 tumors from patients with non-small cell lung cancer who underwent operations. RESULTS: With respect to membranous immunostaining, 57 carcinomas were E-cadherin-positive, 39 carcinomas E-cadherin-reduced, and 13 carcinomas E-cadherin-negative. The percentage of poorly differentiated tumors in the impaired E-cadherin expression group was significantly higher than that in the E-cadherin-positive group (p = 0.005). Furthermore, the frequency of lymph node metastases in tumors with impaired E-cadherin expression was significantly higher than that in the E-cadherin-positive tumors (p = 0.011). A Cox regression analysis revealed that E-cadherin expression was a significant factor in the prediction of survival for patients with non-small cell lung cancer (p = 0.002). CONCLUSIONS: E-Cadherin expression was associated with tumor differentiation, lymph node metastasis, and prognosis in patients with non-small cell lung cancer.

Cadherins↗

[A case of non-invasive pulmonary aspergillosis that rapidly deteriorated].

The pulmonary diseases caused by the Aspergillus species include invasive forms, for example, invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and non-invasive pulmonary aspergillosis. Though these forms are defined pathologically by the presence of the Aspergillus species that invades the lung tissue, they are used as clinical entities. We report a case of non-invasive pulmonary aspergillosis which, from the clinical data, appeared likely to be misdiagnosed as the chronic invasive form. A 45 year-old man received chemoradiotherapy for lung cancer as well as undergoing an left upper lobectomy. Two weeks after the surgery the patient developed a cough, high fever and chest pain. Chest radiography and chest computed tomography showed a rapidly enlarging cavity with an internal mass and infiltration in the left lower lung field. A transbronchial biopsy specimen of the cavity wall showed fungal hyphae. Bronchial washing culture grew Aspergillus fumigatus. Itraconazole and amphotericin B were administered, but the patient's condition did not improve. A left lower lobectomy was performed. The histologic findings showed that the fungal hyphae were only on the surface of the cavity wall, and were surrounded by necrosis and widespread inflammatory cell infiltration. No fungal invasion of the viable lung tissue was seen. The area of infiltration revealed an organizing pneumonia without Aspergillus or other organisms. Our final diagnosis was non-invasive pulmonary aspergillosis. There has been no recurrence of the lung cancer or of the pulmonary aspergillosis in the three years since surgery. It is reported that non-invasive pulmonary aspergillosis passes through a period so active that it seems to be the invasive form for its entire clinical course. To avoid confusion in diagnosis, establishment of a comprehensive clinical classification of pulmonary aspergillosis will be needed.

Aspergillosis↗

Surgical management of pulmonary aspergilloma. Role of single-stage cavernostomy with muscle transposition.

OBJECTIVE: We reviewed the outcome of the patients with aspergilloma who were treated surgically. METHODS: Between July 1991 and October 1996, 11 patients with pulmonary aspergilloma underwent surgery. One underwent sequential bilateral tboracotomy and two underwent re-operation. The total number of operations was 14. Surgical procedures consisted of 5 cavernostomies with muscle transposition, 3 cavernostomies with muscle transposition and thoracoplasty, 1 lobectomy 1 pneumonectomy, 1 segmentectomy and 3 partial resections. RESULTS: Morbidity and mortality rates were 28.6% and 7.1%, respectively Two patients who underwent cavernostomy and muscle transposition experienced a relapse of aspergilloma 19 and 29 months after the operation, respectively, but both successfully underwent re-operation, including cavernostomy. Both are free of symptoms 28 and 30 months after re-operation, respectively. All survivors except for one who died of multiple organ failure remain free of symptoms 14 to 60 months after the most recent operation. CONCLUSION: Our experience was not a controlled trial and two relapsed cases had undergone cavernostomy, our series may suggest that single-stage cavernostomy with muscle transposition is a viable surgical option for patients with pulmonary aspergilloma.

Aged↗

Recovery of parathyroid function after total thyroidectomy.

To prevent postoperative hypoparathyroidism following total thyroidectomy, the parathyroid glands are preserved in situ and/or resected or devascularized parathyroid glands are autotransplanted. We conducted a retrospective investigation utilizing biochemical and specific endocrine assessments to evaluate the difference in recovery of parathyroid function between the two operative methods. A total of 92 patients underwent total thyroidectomy at our hospital during the period between 1990 and 1997. These patients were divided into a preservation group (n = 83), with one or more preserved glands in situ, and an autotransplantation group (n = 9), with only transplanted glands. The level of intact parathyroid hormone (PTH) was completely restored by 1 year postoperatively in 83% (69/83) of the preservation group patients. In the remaining 14 patients (17%), the intact PTH had fallen below detectable levels on postoperative day (POD) 1, then subsequently recovered to 70% of the preoperative levels. Comparatively, in the autotransplantation group, the mean level of intact PTH recovered to only 43% of the preoperative levels. The results of this study suggest that parathyroid glands should be preserved in situ whenever possible, and that when intact PTH levels fall below detectable limits on POD 1, they may never recover to the preoperative levels in those patients.

Adenocarcinoma, Follicular↗

Intratumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung cancer patients treated with 5-FU-based chemotherapy.

5-fluorouracil (5-FU) has been used widely, including in gastrointestinal cancer, breast cancer, and non-small cell lung cancer (NSCLC), and its efficacy has been reported to be associated with intratumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In order to clarify the clinical value of their expression in NSCLC patients treated with 5-FU, we investigated intratumoral expression of TS and DPD immunohistochemically. Of the 68 tumors studied, 40 carcinomas (58. 8%) had high TS expression, and 33 carcinomas (48.5%) had high DPD expression. The 5-year survival rate of the patients with high-TS tumors was significantly lower than that of the patients with low-TS tumors (P=0.0267), and the 5-year survival rate of the patients with high-DPD tumors was significantly lower than that of the patients with low-DPD tumors (P=0.0268). The Cox regression analysis of prognostic variables for NSCLC patients treated with 5-FU demonstrated that the simultaneous evaluation for both TS and DPD expression was found to be a significant indicator of a poor prognosis (P=0.0043). Our results demonstrated that the evaluation of intratumoral TS and DPD activity can be used to accurately predict responsiveness to 5-FU-based chemotherapy in NSCLC patients.

Adult↗

Lung abscess caused by Paecilomyces lilacinus.

We report the case of a 57-year-old man who was referred to our department for further investigation of an abnormal chest shadow. Radiography on admission demonstrated a coin lesion in the right hilum. To make a final diagnosis, right middle lobectomy was performed and the mass was revealed to be a fungal abscess. Further examination confirmed that the fungus was Paecilomyces lilacinus. This is the first reported case of lung abscess caused by P. lilacinus in an otherwise healthy person.

Humans↗

Primary bronchopulmonary fibrosarcoma: report of a case.

We herein report a case of primary bronchopulmonary fibrosarcoma in a 70-year-old man. The patient was referred to our hospital for investigation of hemosputum and an abnormal shadow. On admission, chest radiograph and computed tomography scan showed a mass lesion in right S3 and an infiltrative shadow in the right upper lobe. Transbronchial biopsy specimens showed findings of malignancy, and adenocarcinoma was suspected. A right pneumonectomy was performed, and pathologic examination confirmed a diagnosis of fibrosarcoma. The patient had an uneventful recovery and no sign of recurrence has been found in the year since his operation, although strict follow-up is essential.

Aged↗

[Acute mediastinitis due to esophageal perforation--a case report].

A 55-year-old female consulted her family physician because of pharyngeal discomfort after eating a fish. She underwent rigid fiberscopy and was pointed out a fish bone. Family physician failed to extract the bone and the patient was referred to our hospital. However, there was no fish bone in the esophagus when she underwent second rigid fiberscopy. After eight days she complained of dyspnea and was referred to our hospital again. Chest X ray film showed marked enlargement of the mediastinum and she was diagnosed as acute mediastinitis. She underwent mediastinal drainage by thoracotomy. So tiny perforation was found in cervical esophagus by endoscopy that primary suture was not done. After two months' follow up with intravenous hyperalimentation, there was still esophageal perforation. She underwent the second operation of primary closure with reinforcement using sternocleidomastoid muscle. Two weeks after the second operation esophagogram still showed a fistula. So she received injections of alprostadil and factor XIII. One month after the injections esophagogram showed a diverticulum without leakage.

Acute Disease↗