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Biomedical subjects

Y Monden

Publications and source records attributed to Y Monden.

At least 37 records · Page 2Linked to original sources
PubMed2000

Granulocyte/macrophage-colony-stimulating factor augments lymphokine-activated killer activity from lymphocytes via macrophages in lung cancer patients.

INTRODUCTION: Therapies with granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin(IL)-2 are designed to activate macrophages and lymphocytes. We investigated whether combined treatment with GM-CSF and IL-2 induced macrophage-mediated antitumor activity and/or T-cell-mediated antitumor activity in lung cancer patients. PATIENTS AND METHODS: Macrophages in the pleural cavity (PCM), lymphocytes in the pleural cavity (PLY), and peripheral blood lymphocytes (PBL) were separated from 48 patients with resectable lung cancer. Lymphokine-activated killer (LAK) activity was assayed by measuring 51Cr release. The proportion of PCM positive for the GM-CSF receptor (GM-CFSR) alpha chain was examined by flow-cytometric analysis and the expression of GM-CSFR alpha chain mRNA in PCM was examined by reverse transcription/polymerase chain reaction analysis. RESULTS: Treatment with GM-CSF developed no significant antitumor activity in PCM, PLY, or PBL. LAK activity was developed by PLY and PBL after incubation with IL-2. Stimulation with GM-CSF augmented LAK activities in PLY and PBL significantly, when these cells were cultured with autologous PCM (P < 0.05, P < 0.01). Moreover, GM-CSFR-alpha-chain-positive PCM had a higher potential to augmented LAK activities in PLY and PBL than had GM-CSFR-alpha-chain-negative PCM. CONCLUSION: These findings suggest that GM-CSF may stimulate GM-CSFR-alpha-chain-positive PCM and that these PCM may augment LAK activities developed by PLY and PBL. Combined treatment with GM-CSF and IL-2, therefore, may be a reasonable approach to treating lung cancer patients.

Adult↗
PubMed2000

Artificial lymphogenous metastatic model using orthotopic implantation of human lung cancer.

BACKGROUND AND METHODS: We established a new, patientlike orthotopic model of lung cancer metastasis with human non-small cell lung cancer cell lines. In this report, we describe the progressive stages of development of lymphogenous mediastinal metastasis in the Ma44-3 cell line from day 3 to day 15 after implantation in severe combined immunodeficiency mice and the process of lymphogenous metastasis. RESULTS: All mice killed after day 12 had perivascular and peribronchial tumor growth. Micrometastasis to the mediastinum was first observed on day 5. On days 5 through 9, 10 of 13 mice had metastasis to the mediastinum, and all mice had one by day 12. When perivascular and peribronchial tumor growth was present by day 5, metastasis to the mediastinum developed in all mice. CONCLUSIONS: This study demonstrates the lymphogenous spread of human lung cancer in severe combined immunodeficiency mouse using an orthotopic implantation model. Our model was thought to be an artificial lymphogenous metastasis model, owing to forced tumor inoculation into lymphatic vessels.

Aged↗
PubMed2000

Induction of apoptosis and inhibition of DNA topoisomerase-I in K-562 cells by a marine microalgal polysaccharide.

We have previously purified an extracellular polysaccharide, D-galactan sulfate associated with L(+)-lactic acid, produced from a marine microalga Dinoflagellate Gymnodinium sp. A3 (GA3). The GA3 polysaccharide, irrespective of presence or absence of lactic acid, exhibited significant cytotoxicity, which is based on an induction of apoptotic cell death, toward human myeloid leukemia K562 cells. Furthermore, we found that the GA3 polysaccharide with or without lactic acid possesses an inhibitory effect on topoisomerase-I (topo-I). The potent cytotoxic effect of GA3 polysaccharide may result from its inhibitory effect on topo-I, because the topo-I inhibition is known to trigger apoptotic cell death.

Animals↗
PubMed2000

Identification of hepatic tamoxifen-DNA adducts in mice: alpha-(N(2)-deoxyguanosinyl)tamoxifen and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide.

Tamoxifen-DNA adducts detected in the liver of mice treated with tamoxifen have not yet been identified. In the present study a new type of tamoxifen-DNA adduct, four stereoisomers of alpha-(N:(2)-deoxyguanosinyl)tamoxifen N:-oxide 3'-monophosphate (dG(3'P)-N:(2)-TAM N:-oxide) were prepared as standard DNA adducts by reacting 2'-deoxyguanosine 3'-monophosphate with trans-alpha-acetoxytamoxifen N:-oxide in addition to four stereoisomers of alpha-(N:(2)-deoxyguano- sinyl)tamoxifen 3'-monophosphate (dG(3'P)-N:(2)-TAM) that was reported previously. Liquid chromatography-electrospray ionization-mass spectrometry of the reaction products gave the most abundant ion at m/z 731 ([M - H](-)), which corresponded to dG(3'P)-N:(2)-TAM N:-oxide. The modified products digested by alkaline phosphatase corresponded to the isomers of dG-N:(2)-TAM N:-oxide whose structures were identified previously by mass spectrometry and nuclear magnetic resonance. Using these standard markers, we analyzed the hepatic DNA adducts of female DBA/2 mice treated with tamoxifen at a dosage of 120 mg/kg/day for 7 days by (32)P-post-labeling coupled with an HPLC/radioactive detector. Mixtures of eight isomers of dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N-oxide were separated into six peaks, since each of the cis epimers were not separated under the present HPLC conditions. Nine adducts were detected in all liver samples of mice. An epimer of trans-dG(3'P)-N:(2)-TAM was detected as the principal DNA adduct at a level of 29.0 adducts/10(8) nucleotides, which accounted for 53.3% of the total tamoxifen-DNA adducts. Lesser amounts of cis-dG(3'P)-N:(2)-TAM (2.8%) were also observed. An epimer of the trans-dG(3'P)-N:(2)-TAM N:-oxide (3.9 adducts/10(8) nucleotides) was detected as the third biggest adduct (7.2% of the total). The cis-dG(3'P)-N:(2)-TAM N:-oxide (0.4 adducts/10(8) nucleotides) accounted for 0.7% of the total. Thus, dG(3'P)-N:(2)-TAM and dG(3'P)-N:(2)-TAM N:-oxide were identified in tamoxifen-treated mouse liver.

Animals↗
PubMed2000

[Rare subtype of lung carcinoma].

Rare subtypes of lung cancer, that is, carcinoid, adenoid cystic carcinoma, muco-epidermoid carcinoma and adenosquamous carcinoma, were described. These tumors except adenosquamous carcinoma, are generally low malignant and slow growing and arise from upper airway. Complete surgical resection is the best treatment. Sometime tracheobronchoplastic surgery is recommended. Adenosquamous carcinoma is more malignant than adenocarcinoma or squamous carcinoma.

Carcinoid Tumor↗
PubMed1999

Human MMH (OGG1) type 1a protein is a major enzyme for repair of 8-hydroxyguanine lesions in human cells.

8-Hydroxyguanine (8-OH-G) is the site of a frequent mutagenic lesion of DNA, produced by oxidative damage. MutM of E. coli and OGG1 of Saccharomyces cervisiae are known to possess 8-OH-G glycosylase activity and apurinic (AP) site lyase activity to repair 8-OH-G lesions. Recently, cDNA clones of human OGG1 homologues (hMMH) of four isoforms (type 1a, type 1b, type 1c, and type 2) were isolated. However, it is unknown whether expression of endogenous hMMH proteins actually occurs in mammalian cells. Here using hMMH type 1a-specific antibody and cells overexpressing tag-fused hMMH type 1a, we show the expression of hMMH type 1a protein in many types of human cells and show that endogenous hMMH type 1a protein has 8-OH-G glycosylase/AP lyase activity. Furthermore, we show that upon depletion of hMMH type 1a protein in a whole cell extract by its antibody, most of the AP lyase activity is lost, indicating that hMMH type 1a protein is a major enzyme for repair of 8-OH-G lesions in human cells.

Antibodies↗
PubMed1999

ret/PTC expression may be associated with local invasion of thyroid papillary carcinoma.

BACKGROUND AND OBJECTIVES: The exact role of ret/PTC in the development of papillary carcinoma remains unclear. Expression of the ret/PTC oncogene was examined immunohistochemically to address its role in the progression of thyroid carcinomas. METHODS: Paraffin-embedded samples from 34 clinically evident thyroid papillary carcinomas and 19 occult papillary carcinomas were analyzed using an antibody raised against the ret tyrosine kinase domain. RESULTS: Expression of ret/PTC was demonstrated in 6/19 (32%) occult carcinomas. The frequency of expression of ret/PTC in clinically evident carcinomas in 16/34 (47%) was significantly higher than in normal tissues (0%) and follicular adenomas (1/14, 7%, P < 0.01).ret/PTC expression was observed more frequently in the peripheral areas of clinically evident carcinomas (P < 0.01). Although there was no correlation of ret/PTC expression with tumor size, lymph node metastasis, or distant metastasis, the incidence of ret/PTC expression in tumors with extrathyroidal invasion (13/19, 68%) was significantly higher than those without extrathyroidal invasion (3/15, 20%, P < 0.01). Local invasion was found in none of the occult carcinomas. The frequency of expression in occult carcinomas was significantly lower than in clinically evident carcinomas with extrathyroidal invasion (P < 0.05). CONCLUSIONS: The ret/PTC oncogene may be involved in the local invasion of thyroid papillary carcinomas.

Adenoma↗
PubMed1999

A case of resectable lung adenocarcinoma associated with sarcoidosis.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

Adenocarcinoma↗
PubMed1999

Mediastinal esophageal cyst causing unilateral hyperlucent lung.

Unilateral emphysema secondary to bronchial obstruction by a foregut-derived mediastinal cyst is rare. Here we describe an infant with a unilateral hyperlucent lung due to compression on the left main bronchus by an esophageal cyst, visualized by chest computed tomography and magnetic resonance imaging. A chest roentgenogram and a perfusion scan presented the normalized left lung after resection of the cyst.

Esophageal Cyst↗
PubMed1999

Tamoxifen-DNA adducts formed by alpha-acetoxytamoxifen N-oxide.

DNA adduct formation is assumed to be a major carcinogenic event, leading to the development of endometrial cancer in breast cancer patients taking tamoxifen and healthy women enrolled in a tamoxifen chemopreventive trial. To determine whether DNA adducts were formed by tamoxifen, trans- and cis-alpha-acetoxytamoxifen N-oxides were synthesized as model-activated forms via major tamoxifen metabolites, tamoxifen N-oxide and alpha-hydroxytamoxifen N-oxide. When alpha-acetoxytamoxifen N-oxide was reacted with human DNA, at least three DNA adducts were detected by (32)P-postlabeling coupled with HPLC. The total amount of DNA adducts formed by trans-alpha-hydroxytamoxifen N-oxide was 1.5-fold higher than that formed by the cis form. Both trans- and cis-alpha-acetoxytamoxifen N-oxide reacted with 2'-deoxyguanosine, resulting in the formation of three adducts (fr-1, fr-2-1, and fr-2-2). These products were studied using mass spectroscopy and proton magnetic resonance spectroscopy. fr-1 was identified as a mixture of the epimers of trans-alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide. fr-2-1 and fr-2-2 were determined to be epimers of cis-alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide.

Acetylation↗
PubMed1999

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗
PubMed1999

Comparison of endoscopic features of early-stage squamous cell lung cancer and histological findings.

Seventy cases with early-stage central-type squamous cell carcinoma were treated surgically between 1984 and 1993 in seven participating institutes. We classified endoscopic features of early-stage central-type squamous cell carcinoma into three types (hypertrophic type, nodular type and polypoid type). After surgery we investigated the relationship between endoscopic features and both the area of superficial extent and depth of carcinoma invasion based on histopathological investigations of the surgical specimens. In 66.7% of the hypertrophic type lesions cancer cells did not invade into the cartilaginous layer, and only 4.8% of this type showed tumour invasion beyond the bronchial cartilage. On the other hand, a few nodular and polypoid type cases showed in-situ carcinoma or carcinoma with invasion from the subepithelial layer to the muscle layer, and in approximately 20% the these types we observed carcinoma invasion beyond the cartilaginous layer, which was not suitable for photodynamic therapy. Also, concerning the greatest dimension 24 out of 35 lesions (68.6%) less than 10 mm in the greatest dimension were evaluated as either in-situ carcinoma or micro-invasive tumour within the muscle layer. The endoscopic features can provide a basis for the determination of therapeutic strategy in early-stage central-type lung cancer.

Aged↗
PubMed1999

Azatyrosine. Mechanism of action for conversion of transformed phenotype to normal.

Azatyrosine [L-beta-(5-hydroxy-2-pyridyl)-alanine] has the unique property of converting ras- or c-erbB-2 transformed phenotype to normal. The administration of azatyrosine also inhibits tumor formation in transgenic mice harboring the normal human c-Ha-ras which is mutated during treatment with various chemical carcinogens. To elucidate the molecular mechanism, we investigated how azatyrosine functions and what are its major targets. Azatyrosine functions downstream of ras; azatyrosine does not alter either the level of GTP-bound Ras or the total amount of Ras. Instead, azatyrosine inhibits the activation of c-Raf-1 kinase by oncogenic c-ErbB-2, resulting in inactivation of AP1. It is interesting that azatyrosine also restores the expression of the rhoB gene, the product of which regulates the formation of actin stress fibers. Azatyrosine is incorporated into cellular proteins to replace tyrosine. Several experiments indicate that replacement of tyrosine is likely to be a cause for its conversion of transformed phenotype to normal. To prove this hypothesis, we are attempting to develop a mutant of tyrosyl-tRNA synthetase that, unlike wild type, can aminoacylate azatyrosine more efficiently than can tyrosine.

Alanine↗
PubMed1999

New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.

AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface.

Administration, Cutaneous↗
PubMed1999

Two cases of repeatedly recurrent atypical thymoma.

Two cases of repeatedly recurrent thymoma with myasthenia gravis are detailed here. A 41-year-old woman had 5 recurrent thymomas, including local recurrences and lumbar and lung metastases; she was alive at the time of this writing, which was 22 years after her first surgery. A 36-year-old man had 3 recurrent thymomas, including local recurrence, dissemination, and lung metastasis; he was alive at the time of this writing, which was 16 years after his first surgery. Both recurrent lesions were diagnosed as "atypical thymoma" with moderate nuclear atypia. The patients with atypical thymoma must be followed up carefully due to a possible recurrence. Surgical treatment with chemoradiotherapy can lengthen their survival.

Adult↗
PubMed1999

[Controversies in the new TNM staging system].

The latest revision of the International System for Staging Lung Cancer was published in June 1997. We discuss the following 4 major items in the new TNM staging system. 1) The fact that stage I was divided into stage IA (T1N0M0) and IB (T2N0M0) is reasonable, as the survival prospects for the subsets differ significantly. 2) The fact that stage II was divided into stage IIA (T1N1M0) and IIB (T2N1M0) is not appropriate, However, there is no significant survival difference between the T1N1M0 subset and the T2N1M0 subset, because there are fewer T1N1M0 cases. 3) The fact that the T3N0M0 subset was shifted into stage IIB is reasonable. Patients who undergo resection of tumors invading the parietal pleura, neighboring lobe, and main bronchus within 2 cm of the carina in the T3N0M0 group have a good prognosis, but those who undergo resection of tumors invading the rib, intercostal muscle, and diaphragm in the T3N0M0 group have a poor prognosis. 4) The decision to designate satellite lesions within the lobe of the primary tumor as T4 is controversial, because it is very difficult to determine whether satellite lesions are metastases from other lesions or if they are primary synchronous neoplasms.

Humans↗
PubMed1999

Late recurrence of acinic cell carcinoma of the parotid gland.

Acinic cell carcinoma of the salivary glands is a rare cancer representing a low grade malignancy. The recurrence of a tumor is sometimes encountered, usually within 5 years of initial operation. We describe an unusual recurrence after a long interval following primary surgery. In 1987, a 60-year-old woman underwent excision of a mass in the superficial lobe of the right parotid gland under the preoperative diagnosis of a benign tumor. A histologic diagnosis of acinic cell carcinoma was made by examining sections from the resected mass. The patient noted several small nodules in the right parotid region in 1995, but she did not visit our clinic until 1998 when tenderness developed. A locally recurrent tumor and cervical lymph nodes containing metastases were resected and postoperative radiotherapy was given 11 years after the first operation. At least 10 years of follow-up may be necessary for patients with acinic cell carcinoma because of slow-tumor growth.

Carcinoma, Acinar Cell↗