Search PubMed⌕ Search

Biomedical subjects

K Fukuoka

Publications and source records attributed to K Fukuoka.

At least 19 recordsLinked to original sources
PubMed2002

Effects of gonadotropin-releasing hormone analog treatment on skin condition.

The skin is a target organ of estrogens. Thus, theoretically, a hypoestrogenic state induced by gonadotropin-releasing hormone analog (GnRHa) treatment may have effects on skin condition. The aim of this study was to evaluate skin condition during GnRHa treatment. Sixteen premenopausal women undergoing GnRHa treatment for 16 weeks, as a presurgical treatment for uterine leiomyomas, were studied. Measurement of serum estradiol levels and epidermal hydration, and evaluation of subjective findings on skin condition using a questionnaire, were performed every 4 weeks during the treatment period. Serum estradiol levels were significantly suppressed at 4 weeks of treatment, and remained low afterwards. Epidermal hydration measured by corneometer did not show any significant difference at any time point examined, compared with that before treatment. No particular subjective findings relating to the skin (dryness, wrinkling, roughness, pigmentation, itching, formication, reaction to cosmetics) were reported during treatment, whereas complaints about hot flushes and sweating were notable. The results of this preliminary study support the notion that GnRHa treatment for 16 weeks is unassociated with apparent changes in skin condition.

Adult↗
PubMed2001

Mechanism of the radiosensitization induced by vinorelbine in human non-small cell lung cancer cells.

Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate radiosensitization produced by vinorelbine in human non-small cell lung cancer (NSCLC) PC-9 cells and to elucidate the cellular mechanism of radiosensitization. A clonogenic assay demonstrated that PC-9 cells were sensitized to radiation by vinorelbine with a maximal sensitizer enhancement ratio at a 10% cell survival level of 1.35 after 24-h exposure to vinorelbine at 20 nM. After 24-h exposure to vinorelbine at 20 nM, the approximately 67% of the cells that had accumulated in the G2/M-phase were cultured in the absence of vinorelbine and then irradiated at a dose of 8 Gy. Flow cytometric analyses showed prolonged G2/M accumulation concomitant with continuous polyploidization, and induction of apoptosis was observed in the cells subjected to the combination of vinorelbine-pretreatment and radiation. Polyploidization and induction of apoptosis were confirmed by morphological examination and a DNA fragmentation assay, respectively. We concluded that vinorelbine at a minimally toxic concentration moderately sensitizes human NSCLC cells to radiation by causing accumulation of cells in the G2/M-phase of the cell cycle. Prolonged G2/M accumulation concomitant with continuous polyploidization and increased susceptibility to induction of apoptosis may be associated with the cellular mechanism of radiosensitization produced by vinorelbine.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Mechanisms of action of the novel sulfonamide anticancer agent E7070 on cell cycle progression in human non-small cell lung cancer cells.

E7070 is a novel sulfonamide antitumor agent that exhibits potent antitumor activity in vitro and in vivo. This compound affects cell cycle progression in human tumor cells. To elucidate the mechanisms by which E7070 inhibits tumor cell growth, we established and characterized an E7070-resistant subline, A549/ER, from a human non-small cell lung cancer cell line A549. Flow cytometric analyses demonstrated an increase in G0/G1 and a decrease in S phase populations in cells treated with E7070 at 20 or 100 microg/ml for 24 h. Longer exposure to E7070, i.e. 48 and 72 h, increased the G2/M phase fraction in A549 cells. These inhibitory actions of E7070 on cell cycle progression were not observed in A549/ER cells. E7070 inhibited the phosphorylation of pRb, decreased expressions of cyclin A, B1, CDK2, and CDC2 proteins, and suppressed CDK2 catalytic activity with the induction of p53 and p21 proteins in A549 cells but not in A549/ER cells. Taken together, these results suggest that E7070 exerts its antitumor effects by disturbing the cell cycle at multiple points, including both the G1/S and the G2/M transition, in human lung cancer cells.

Antineoplastic Agents↗
PubMed2001

Changes in the number of gut mucosal T-lymphocytes and macrophages in patients treated by external biliary drainage.

OBJECTIVE: To examine the changes in the number of T cells and macrophages in the mucosal lamina propria in the presence or absence of bile in the gastrointestinal tract. DESIGN: Clinical study. SETTING: University hospital, Japan. SUBJECTS: 6 patients with obstructive jaundice who had external biliary drainage (drainage group) and 6 patients with no signs of obstructive jaundice (control group). INTERVENTIONS: Gastrointestinal specimens were taken at the time of operation. MAIN OUTCOME MEASURES: The number of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the lamina propria mucosae in each group measured immunohistochemically. RESULTS: The numbers of CD8 T cells and CD68+ macrophages in the lamina propria of the patients treated by external drainage were significantly less than in the control group (p < 0.01). However, there was no difference in the number of CD4+ T cells between the groups (p = 0.45). CONCLUSIONS: In the absence of bile, mucosal immune function fails as a result of reduced numbers of CD8+ T cells and macrophages.

Aged↗
PubMed2001

Enhancement of in vivo antitumor activity of a novel antimitotic 1-phenylpropenone derivative, AM-132, by tumor necrosis factor-alpha or interleukin-6.

TK5048 and its derivatives, AM-132, AM-138, and AM-97, are recently developed antimitotic (AM) compounds. These 1-phenylpropenone derivatives induce cell cycle arrest at the G2 / M phase of the cell cycle. TK5048 inhibited tubulin polymerization in human lung cancer PC-14 cells in a concentration-dependent manner. In a polymerization assay using bovine brain tubulin, AM-132 and AM-138 were quite strong, AM-97 was moderately strong, and TK5048 was a relatively weak inhibitor of tubulin polymerization. A murine leukemia cell line resistant to a sulfonamide antimitotic agent, E7010, which binds to colchicine-binding sites on tubulin, was cross-resistant to the in vitro growth-inhibitory effect of AM compounds. Inhibition of tubulin polymerization is therefore one of the mechanisms of action of these AM compounds against tumor cells. To profile the antitumor effect of AM compounds, the in vivo antitumor effect of AM-132 was evaluated against cytokine-secreting Lewis lung carcinoma (LLC). Tumor-bearing mice were treated with intravenous AM-132 using three different treatment schedules. LLC tumors expressing tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage colony-stimulating factor (GM-CSF), or interleukin (IL)-6 were very sensitive to AM-132. In particular, LLC tumors expressing IL-6 were markedly reduced by AM-132 treatment, and showed coloring of the tumor surface and unusual hemorrhagic necrosis. These results suggest a combined effect of AM-132 and cytokines on the blood supply to tumors.

Animals↗
PubMed2000

Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G(1) phase of the cell cycle.

Aragusterol A (YTA0040), isolated from the Okinawan marine sponge of the genus Xestospongia, is a potent anti-tumor marine steroid that possesses a unique structural component. This compound showed broad-spectrum anti-proliferative activity against a panel of 14 human cancer cell lines (IC(50) = 0.01-1.6 microM). P-glycoprotein-mediated, multidrug-resistant cells showed cross-resistance to YTA0040 cells, whereas cisplatin-resistant non-small-cell lung-cancer (NSCLC) sublines showed a collateral sensitivity to YTA0040. In transplantable murine tumor models, YTA0040 displayed a broad spectrum and high degree of anti-tumor activity when administered i.p. or p.o. (life span T/C = 135-234%). In P388 murine leukemia cells, YTA0040 caused dose- and time-dependent suppression of nucleic acid and protein synthesis, with protein synthesis being more potently and rapidly inhibited than nucleic acid synthesis. Flow-cytometric analysis revealed that YTA0040 blocked the entry of human NSCLC-derived A549 cells into S phase, leading to arrest in the G(1) phase of the cell cycle. Western blot analysis demonstrated that YTA0040 caused a dose-dependent decrease in the levels of expression of hyperphosphorylated pRb and cyclin A in A549 cells. The level of p53 protein expression was decreased by YTA0040 treatment. A higher concentration of YTA0040 down-regulated the levels of expression of CDK2, CDK4, cyclin D1 and cyclin E. These findings indicated that YTA0040 arrested human NSCLC cells in late G(1) phase of the cell cycle through inhibition of pRb phosphorylation. Inhibition of pRb phosphorylation by YTA0040 resulted from down-regulation of levels of expression of the CDKs and cyclins involved in the G(1)/S transition and not from induction of p53 and/or the CDK inhibitor p21.

Animals↗
PubMed2000

Ectopic p16(ink4) expression enhances CPT-11-induced apoptosis through increased delay in S-phase progression in human non-small-cell-lung-cancer cells.

A tumor-suppressor gene, p16(INK4), which is deleted or mutated in tumors, regulates cell-cycle progression through a G(1)-S restriction point by inhibiting CDK4(CDK6)/cyclin-D-mediated phosphorylation of pRb. We have found that ectopic p16(INK4) expression increased cellular sensitivity of human non-small-cell-lung-cancer (NSCLC) A549 cells to a selective growth-inhibitory effect induced by the topoisomerase-I inhibitor 11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11) in vitro. In this study, we observed enhanced apoptosis characterized by DNA fragmentation in A549 cells transfected with p16(INK4) cDNA (A549/p16-1) and treated with CPT-11. This apoptosis was suppressed by the inhibitor of interleukin-1beta-converting enzyme (ICE/caspase-1) or ICE-like proteases, Z-Asp-CH2-DCB, as determined by DNA fragmentation and proteolytic cleavage of poly(ADP-ribose) polymerase, a natural substrate for CPP32/caspase-3. In A549/p16-1 cells, cytosolic peptidase activities that cleaved Z-DEVD-7-amino-4-trifluoromethylcoumarin increased during CPT-11-induced apoptosis and were suppressed by a highly specific caspase-3 and caspase-3-like inhibitor, Z-DEVD-fluoromethylketone. These findings indicate that p16(INK) is positively involved in the activation pathway of the caspase-3 induced by CPT-11. The increased delay in S-phase progression and subsequent induction of apoptosis were observed in CPT-11-treated A549/p16-1 cells on the basis of DNA histograms. Specific down-regulation of the cyclin-A protein level in A549/p16-1 cells was observed after CPT-11-treatment, whereas cyclin B, cdk2, and cdc2 protein levels were unaffected. These results suggest that ectopic p16(INK4) expression inappropriately decreases cyclin A and thereby terminates CPT-11-induced G(2)/M accumulation, which is followed by increased apoptosis in p16(INK4)-expressing A549 cells.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Molecular determinants of UCN-01-induced growth inhibition in human lung cancer cells.

UCN-01 (7-hydroxystaurosporine) inhibits the growth of various malignant cell lines in vitro and in vivo. In this study, a human small cell lung carcinoma subline resistant to UCN-01, SBC-3/UCN, was established and characterized. SBC-3/UCN cells showed 8-fold greater resistance to the UCN-01-induced growth-inhibitory effect than the parent cells, SBC-3. No UCN-01-induced G1 accumulation in SBC-3 cells was observed in SBC-3/UCN cells and decreased expression of phosphorylated RB protein was found in SBC-3 cells. Neither basal expression nor induction of p21(Cip1) by UCN-01 treatment was detected in the SBC-3/UCN cell line. An inhibitory effect of UCN-01 on CDK2 activity, which is mediated by p21(Cip1)/CDK2 complex formation upon UCN-01 treatment, was observed in SBC-3 but not in SBC-3/UCN cells. SBC-3/UCN showed higher CDK6 activity than SBC-3 cells. UCN-01 did not inhibit the CDK4 and CDK6 activities in both cells. We screened the cell cycle regulatory molecules associated with G(1)/S progression and found a remarked decrease in interferon regulatory factor 1 (IRF-1), which is known to cooperate with p53 in p21(Cip1) induction. Our results suggest that p21(Cip1) regulation via the IRF-1-associated pathway may represent a major determinant of UCN-01-induced growth inhibition in human lung cancer cells.

Alkaloids↗
PubMed2000

Cytology of microcystic meningioma in crush preparation.

Microcystic meningioma is a rare variant of meningioma, showing microcystic formations throughout the tumor. To the best of our knowledge, there have been no reports describing cytologic findings of microcystic meningioma. Our case was a 66-yr-old woman with a tumor mass adhered to the dura matter. The crush preparations of a small tissue fragment resected from the mass showed medium- to large-sized, well-cohesive clusters or sheets of uniform tumor cells. The tumor cells did not show a feathering-off pattern. Various-sized cystic spaces were observed within the clusters and sheets. The cytoplasm was relatively abundant, and the nuclear:cytoplasmic ratio was lower than that of classic meningioma. We believe that the cystic spaces within the cell clusters or sheets are characteristic of microcystic meningioma. The cytology of microcystic meningioma seen in our case was similar to that of metastatic adenocarcinoma, but relatively monotonous bland cells, smooth nuclear outline, and inconspicuous nucleoli led us to the diagnosis of meningioma rather than adenocarcinoma.

Aged↗
PubMed2000

Macrocystic serous cystadenoma of the pancreas.

We report a 47-year-old woman with macrocystic serous cystadenoma of the pancreas. She had no past history of abdominal surgery, instrumentation, or trauma. Ultrasonography and computed tomography revealed a unilocular cyst in the body of the pancreas. On magnetic resonance imaging, the cyst showed heterogeneous signal intensity on T1-weighted images, and was homogeneously hyperintense and oligolocular is on T2-weighted images. A preoperative diagnosis of mucinous cystic neoplasm of the pancreas was made, and distal pancreatectomy was performed. The resected oligolocular cyst was 5.0 x 4.5 x 3.0 cm and was lined with a single layer of cuboidal epithelium similar to that seen in microcystic serous cystadenomas. Abundant glycogen was demonstrated within the epithelial cells, as assessed by periodic acid-Schiff (PAS) staining with and without diastase digestion. The cyst exhibited a gross appearance distinct from that of typical microcystic adenomas, resulting in diagnostic difficulties for the radiologists and surgeon involved in the patient's care.

Cystadenoma, Serous↗
PubMed2000

Teratocarcinosarcoma of the nasal cavity. Report of a case showing favorable prognosis.

We report a very rare case of teratocarcinosarcoma of the nasal cavity showing a favorable prognosis. The patient was a 66-year-old man with a mass completely obstructing the right nasal cavity. Subsequently, extirpation of the mass and Denker-Watsuji operation were performed, and the patient was treated with a combination of radiation therapy and chemotherapy. Neither recurrence nor distant metastasis was observed during follow-up lasting 30 months. Histologic examination of the resected mass revealed several tissue elements including columnar and squamous epithelia with atypia, smooth muscle cells with rare mitotic activity, and neuroectodermal tissue. The glandular epithelium and smooth muscle cells were reminiscent of a primitive intestinal organoid structure, suggestive of teratomatous tumorigenesis. Our case and a review of the literature indicate that the absence of invasiveness to the stroma or surrounding tissue is closely related to a favorable prognosis.

Aged↗
PubMed2000

[A case report of lung abscess caused by Capnocytophaga gingivalis infection].

A 48-year-old male was admitted to our hospital because of fever, cough and of loss appetite. Chest X-P revealed an abnormal shadow in the left upper lobe. Bronchoscopy was performed and Capnocytophaga gingivalis was cultured from the bronchial lavage and bronchial curreting fluid. Ceftizoxime sodium and Clindamycin phosphate was administered intravenously. He was discharged after 30 days. He did not have any immunosuppressive underlying disease including HIV infection and diabetes mellitus which cause these lesions.

Capnocytophaga↗
PubMed2000

[Indication and effectiveness of endoscopic percutaneous gastrostomy as a route of parenteral alimentation for the home care patient].

We are managing 8 home care patients who have a gastrostomy made using an endoscopic percutaneous technique as a route of parenteral alimentation. Based on our experience, the preconditions for an endoscopic percutaneous gastrostomy as a route of parenteral alimentation are 1. normal gastrointestinal function, 2. difficulty in swallowing, 3. possibility that the caregiver can manage the gastrostomy. When we performed an endoscopic percutaneous gastrostomy as a route of parenteral alimentation for 8 home care patients, we obtained the several advantages mentioned below. 1. Swallowing pneumonia was prevented. 2. Adequate amount of alimental liquid could be infused. 3. Patient could take a bath or shower with the gastrostomy, and good QOL was realized. 4. The home care patient with the gastrostomy could have a satisfactorily long life.

Aged↗
PubMed1999

Effect of a chimeric anti-ganglioside GM2 antibody on ganglioside GM2-expressing human solid tumors in vivo.

Ganglioside GM2 is expressed on the surface of neuroblastoma and glioblastoma cells, and may also be detected on lung cancer cells. We reported previously that anti-ganglioside GM2 antibody exhibited strong in vitro anti-tumor activity against adriamycin-resistant cancer cells, which overexpressed ganglioside GM2. In the present study, we examined the in vivo anti-tumor effect of the chimeric anti-ganglioside GM2 antibody, KM966, against human lung and breast carcinoma cells, SBC-3 and MCF-7, and respective adriamycin-resistant clones, SBC-3/ADM and AdrR MCF-7 in BALB/c nu/nu mice. Ratios of tumor volume (T/C) between KM966-treated group and control group were 0.01 for SBC-3, 0.00 for SBC-3/ADM, 0.85 for MCF-7 and 0.34 for AdrR MCF-7 cells, respectively. Nude mice, which were pretreated with anti-asialo GM1 antibody to remove natural killer cells, were transplanted with 4 x 10(7) of SBC-3 and SBC-3/ADM subcutaneously. Seven days later, when tumors had grown to a diameter of over 8 mm, mice began to receive intravenous treatment of 120 microgram/mouse KM966 daily. Fourteen daily treatments induced regression to less than 4-mm diameter in 4/5 SBC-3 tumors and 5/5 of SBC-3/ADM tumors. All SBC-3/ADM tumors disappeared completely, suggesting that KM966 exerts a strong in vivo anti-tumor effect on ganglioside GM2-expressing cancer cells. In KM966-treated mice, the surface of the tumor cells stained positive with anti-human IgG. In addition, numerous leukocytes had infiltrated into the tumor mass. Antibody-dependent cell-mediated cytotoxicity (ADCC) of KM966 against tumor cells was examined in vitro by (51)Cr-release assay and revealed that KM966 induces ADCC activity against ganglioside GM2-expressing tumors. Our results suggest that immunotherapy using KM966 may be useful for the treatment of ganglioside GM2-expressing solid tumors.

Animals↗
PubMed1999

In vitro interactions of a new derivative of spicamycin, KRN5500, and other anticancer drugs using a three-dimensional model.

PURPOSE: KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against human cancer cell lines. Because of its unique structure, this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore, KRN5500 is expected to be a suitable candidate for combination chemotherapy. METHODS: We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model. RESULTS: Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 microg/ml and 0.025 to 0.25 microg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic interaction was also found. CONCLUSION: These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.

Antibiotics, Antineoplastic↗
PubMed1999

Combination effects of TAS-103, a novel dual topoisomerase I and II inhibitor, with other anticancer agents on human small cell lung cancer cells.

PURPOSE: TAS-103 [6-((2-(dimethylamino) ethyl)amino)-3-hydroxy-7H-iindeno(2,1-c)quinolin-7-one dihydrochloride] is a newly synthesized dual inhibitor of topoisomerase I and II. Since anticancer drugs are used in combination with other drugs for effective chemotherapy, we investigated the cytotoxic effect of TAS-103 in combination with other conventional anticancer agents, such as cisplatin, vindesine, doxorubicin, 5-fluorouracil, and the antitopoisomerase inhibitors SN-38 and etoposide in vitro. METHODS: Inhibition of the growth of the human small-cell lung cancer cell line SBC-3 was evaluated using the tetrazolium dye (MTT) assay. Drug interactions were evaluated by isobologram analysis and the determination of combination indices supplemented by a three-dimensional model. RESULTS: Simultaneous use of TAS-103 and cisplatin had a supraadditive effect, but combinations of TAS-103 with other drugs had an additive or marginally subadditive effect. Three-dimensional model analysis added more information about the synergistic concentration ranges of two drugs (cisplatin 200-400 nM and TAS-103 7 10 nM). Sequential use of TAS-103 and cisplatin had only an additive effect. CONCLUSION: These results suggest that the concomitant use of TAS-103 and cisplatin has a greater cytotoxic effect on cancer cells than single drug use, and may provide a beneficial effect in the treatment of small-cell lung cancer.

Aminoquinolines↗
PubMed1999

Complete agenesis of the dorsal pancreas.

Pancreatic anomalies are occasionally reported, but complete agenesis of the dorsal pancreas is extremely rare. We report a 47-year-old woman with complete agenesis of the dorsal pancreas. This patient initially presented with jaundice. Computed tomography did not reveal the pancreatic corpus or tail. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography did not visualize the dorsal pancreatic duct. Choledochojejunostomy was performed because she had obstructive jaundice. At laparotomy, there was an enlarged pancreatic head, but no distal pancreas was seen. Histological examination of the pancreatic biopsy specimen showed scattered islets of Langerhans in diffuse fibrosis, with destruction of the glandular parenchyma. This case was diagnosed as complete agenesis of the dorsal pancreas.

Cholangiopancreatography, Endoscopic Retrograde↗