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Biomedical subjects

M Tsukuda

Publications and source records attributed to M Tsukuda.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Preoperative chemotherapy for patients with advanced head and neck cancer].

Cases with head and neck squamous cell carcinoma (HNSCC) have clinically advanced tumors. The curative treatments for advanced HNSCC are radiotherapy and/or surgical resection. However, standard treatment alone is less successful for advanced HNSCC. Accordingly, two modalities using chemotherapy are applied as preoperative treatment for HNSCC. First, multi-drug chemotherapy has been administered as neoadjuvant chemotherapy (NAC). As a result during the past 20 years, NAC without a high complete response (CR) rate has never improved the long-term outcome of advanced cases. Therefore, the development of intensive chemotherapy regimen with a high CR rate including taxanes is ongoing. On the other hand, organ preservation modality has been under investigation using combined radiotherapy with NAC regimen with a dose reduction of administered chemotherapeutic drugs or a new chemotherapy regimen including taxanes (concomitant or concurrent chemoradiotherapy). In this strategy, impact chemotherapy with almost the same anti-tumor effect as NAC and with a potential of radiation sensitizer is necessary.

Antineoplastic Agents↗
PubMed2000

Therapeutic effect of 1 M tegafur-0.4 M 5-chloro-2, 4-dihydroxypridine-1 M potassium oxonate (S-1) on head and neck squamous carcinoma cells.

1 M Tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypridine (CHDP)-1 M potassium oxonate (Oxo) (S-1), was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CHDP and Oxo. The antitumor effect of S-1 on human head and neck squamous carcinoma cells was evaluated in xenografts and a metastasis model, in comparison with combined drug of 1 M FT and 4 M uracil (UFT). Mice treatment with S-1 showed a significant higher concentration of 5-FU in the tumor and the serum than UFT treated mice. S-1 showed higher tumor growth inhibition and metastasis inhibition than UFT. The mice in which metastasis was inhibited lived more than twice as long as the control mice. These results suggest that S-1 will have a higher clinical therapeutic effect against advanced squamous cell carcinoma of the head and neck in humans.

Administration, Oral↗
PubMed2000

Therapeutic efficiency of IL-2 gene transduced tumor vaccine for head and neck carcinoma.

Transduction of the human interleukin-2 (IL-2) gene into tumor cells was carried out in order to develop a new immunotherapy for advanced head and neck carcinomas with a poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using a defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. A high level of IL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2 producibility of irradiated KB/IL-2 cells was almost the same as that of non-irradiated cells. In the tumor establishment model in nude mice, IL-2 and interferon-gamma (IFN-gamma) at high concentrations were detected in the sera of mice transplanted with KB/IL-2 cells. The spleen cells of nude mice transplanted with KB/IL-2 cells exhibited high cytotoxic activity compared to those from mice transplanted with KB cells and from untreated mice. Three of five mice transplanted with KB/IL-2 cells rejected tumors. In the treatment of established tumors, therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumor growth were blocked by anti-asialo GM1, anti-human IL-2 and anti-IFN-gamma antibodies. Immunohistochemical observation revealed the presence of asialo GM1(+) cells among the KB/IL-2 cells in tumors transplanted into nude mice.

Animals↗
PubMed2000

Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, suppresses invasion ability by reducing productions of matrix metalloproteinase-2 and -9 and cell motility in HSC-4 tongue carcinoma cell line.

Inostamycin is an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase. It significantly reduced epidermal growth factor (EGF)-induced in vitro invasion of the tongue carcinoma cell line, HSC-4, through reconstituted basement membrane Matrigel. Since phosphatidylinositol (PI) 4,5-biphosphate is important for signal transduction through protein kinase C and actin reorganisation, we further examined the effect of inostamycin on production of two matrix metalloproteinases (MMPs), MMP-2 and -9, and on cell motility. Zymographic analysis showed that inostamycin suppressed pro-MMP-2 and pro-MMP-9 levels at a dose-dependent fashion, while MMP-2 activity was not significantly affected. By reverse transcription-polymerase chain reaction, it was found that inostamycin diminished steady state levels of MMP-2 and -9 but not membrane type 1-MMP mRNA expressions. Inostamycin partially blocked both EGF- and phorbol 12-myristate 13-acetate-stimulated pro-MMP-9 production. A cytoplasmic calcium chelator (BAPTA-AM) dramatically elevated pro- MMP-9 and slightly elevated pro-MMP-2 secretions. EGF-stimulated motility of HSC-4 cells was suppressed by inostamycin treatment along with reduction of actin cytoskeletal reorganisation, filopodia formation and cdc42 expression. These results suggested that inostamycin would be useful for an anti-invasive agent in tongue cancer.

Base Sequence↗
PubMed2000

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma.

An experimental model of tumor dormancy therapy for advanced head and neck carcinoma was developed. After transplantation of KB cells into nude mice, the mice were given tiracoxib, a selective cyclooxygenase (COX)-2 inhibitor, probucol, an antioxidant, and S-1, an oral pro-drug of 5-fluorouracil (5-FU), or combinations of two of them. The combined administration of tiracoxib with probucol significantly inhibited the tumor growth. The angiogenesis in this group was markedly reduced. Tiracoxib and probucol did not affect the intratumoral concentration of 5-FU when coadministered with S-1. The combined use of tiracoxib and probucol is thus a candidate for use in maintenance therapy after the primary therapy for patients with advanced head and neck carcinoma.

Animals↗
PubMed2000

Treatment of deep vein thrombosis using temporary vena caval filters after allogeneic bone marrow transplantation.

Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.

Anticoagulants↗
PubMed2000

[Cervical lymph node metastasis from an unknown primary tumor].

Between June/1986 and June/1999, we treated 18 cases of previously untreated metastatic carcinoma in cervical lymph nodes from an unknown primary tumor. Among them, 15 cases were squamous cell carcinoma, 2 were adenocarcinoma, and one was undifferentiated carcinoma. The dose of radiotherapy, which was planned only for the cervical lymph nodes, was 60-70 Gy at the metastatic sites. Preventive radiotherapy at possible primary sites was performed only in one case. After these treatments, a primary lesion appeared in only two cases: in one case a tumor was found in the hypopharynx, and the other, which had been diagnosed as undifferentiated carcinoma, proved to be malignant lymphoma. Outcomes were analyzed except for these two cases. The five-year survival rate was 31%. The loco-regional control rate was 57% after radiation treatment limited to the affected cervical lymph nodes. Distant metastasis appeared more often in open-biopsy cases than in those receiving fine-needle aspirations (FNA). According to these results, treatment of possible primary sites may not be necessary, and for initial pathological diagnosis, FNA is recommended, while open biopsy should be avoided, if possible.

Adenocarcinoma↗
PubMed2000

[Antitumor effect of the angiogenesis inhibitor, TNP470, on squamous cell carcinoma cells in head and neck cancer].

The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p < 0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.

Angiogenesis Inhibitors↗
PubMed2000

[Recent regimen of chemotherapy for advanced head and neck carcinomas].

Standard treatment for squamous cell carcinomas in the head and neck consists of surgery and/or radiotherapy. However, this standard treatment alone has not improved the poor prognosis of advanced head and neck carcinomas. A new curative treatment modality for advanced head and neck carcinomas including chemotherapy with an impact is needed. The clinical results of chemotherapy over the past twenty years have shown chemotherapy including cisplatin (CDDP) and 5-fluorouracil (5-FU) to be the most efficacious for advanced cases. In this paper, the problems with this chemotherapy are discussed in terms of predictive factors of the response to this treatment, and the recent clinical results with chemotherapy including CDDP, 5-FU, and other drugs are reviewed. Furthermore, new chemotherapeutic regimens and the clinical results including commonly applied taxanes, e.g., paclitaxel and docetaxel, are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[A randomized crossover comparison of azasetron alone and azasetron plus dexamethasone for the prevention of nausea and vomiting by chemotherapy including cisplatin].

A randomized crossover study between azasetron alone and azasetron combined with dexamethasone was performed to investigate the prevention of nausea and vomiting due to chemotherapy including cisplatin in patients with advanced head and neck carcinoma. The results indicated that the combination therapy with dexamethasone was more effective than azasetron alone in preventing nausea on days 1 through 5 after the administration of cisplatin and was significantly superior to azasetron alone on days 2 and 3. In addition, complete response (no vomiting) and the antiemetic and antinausea efficacy of combination therapy with dexamethasone on day 2 was significantly superior compared to azasetron alone. No adverse effect from either antiemetic therapy was observed in this study.

Adult↗
PubMed1999

P-selectin binding promotes the adhesion of monocytes to VCAM-1 under flow conditions.

This study examined the adhesive interaction of peripheral blood monocytes with VCAM-1 and analyzed the effect of P-selectin binding to monocytes on the adhesive interaction with VCAM-1 under flow conditions. P-selectin glycoprotein ligand-1 is expressed on most monocytes. Furthermore, most monocytes bind soluble P-selectin derived from platelets. P-selectin binding to monocytes did not alter the amount of expression of alpha4 integrin on monocytes. However, the mean channel fluorescence value for binding Cy2-conjugated soluble VCAM-1 to P-selectin-bound monocytes was slightly more than that for binding Cy2-conjugated soluble VCAM-1 to untreated monocytes. Under flow conditions, the number of P-selectin-bound monocytes bound to VCAM-1 was much higher than that of untreated monocytes bound to VCAM-1. These bindings were abolished by pretreatment of untreated monocytes and P-selectin-bound monocytes with anti-VCAM-1 mAb or anti-alpha4 integrin mAb. Furthermore, P-selectin binding to monocytes increased shear resistance and thus increased the adhesive strength of monocytes to VCAM-1. These findings indicate that P-selectin binding to monocytes enhances the adhesive interaction of monocytes with VCAM-1. It is suggested that P-selectin glycoprotein ligand-1/P-selectin interaction and alpha4 integrin/VCAM-1 interaction can act sequentially in the adhesion cascade that regulates monocyte trafficking to inflammatory and atherosclerotic lesion.

Blood Flow Velocity↗
PubMed1999

A selective cyclooxygenase-2 inhibitor suppresses tumor growth in nude mouse xenografted with human head and neck squamous carcinoma cells.

The anti-tumor effect of a selective cyclooxygenase (COX)-2 inhibitor, JTE-522, was examined with the human head and neck squamous cell carcinoma cell line KB. KB cells do not produce prostaglandin (PG)-E2. In vitro, JTE-522 induced an increase of G1 phase-arrested cells, suppression of platelet-derived growth factor (PDGF) production and inhibition of telomerase activity. No cytotoxic effect was detected. In vivo, the growth of the tumor xenografted into nude mice was significantly suppressed by JTE-522. Suppression of angiogenesis at the periphery of the tumor, increase of G1-arrested cells and suppression of telomerase activity were observed, together with an increase of apoptotic cell death in the tumor. Immunological enhancement did not play a role. We concluded that the anti-tumor effect of JTE-522 was caused by anti-angiogenesis action, cell cycle arrest and inhibition of telomerase activity of the tumor cells. These combined effects might induce apoptosis.

Animals↗
PubMed1999

An antioxidant, probucol, induces anti-angiogenesis and apoptosis in athymic nude mouse xenografted human head and neck squamous carcinoma cells.

Probucol is a very strong synthetic antioxidant that was been safely used for the treatment of hyperlipidemia in Japan since 1985. It has been reported that lipid oxidation products can alter growth factor production, which could influence smooth muscle cell proliferation. Oxidized low density lipoprotein can influence smooth muscle cell proliferation by enhancing the expression of platelet-derived growth factor (PDGF)-AA gene and PDGF receptor in vascular smooth muscle cell. Further, free radical reactions can cause irreversible alterations of genomic constituents during the initiation phase of carcinogenesis. Antioxidant is considered to protect lipids and low density lipoprotein (LDL) from oxidation, which potentially inhibits angiogenesis, and rapid removal of free radicals by antioxidants could have an anti-carcinogenic effect. In the present study, we investigated whether antioxidant treatment with probucol had an antitumor effect on KB cells, a human head and neck squamous carcinoma cell line. Probucol did not have any effect on KB cells in vitro, but probucol treatment of KB cells xenografts in mice had a significant antitumor effect through anti-angiogenic and apoptosis-inducing actions. These results support the idea that probucol is useful for preventing and/or treating cancer.

Animals↗
PubMed1999

Changes in the distribution of the substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the laryngeal mucosa of chronically hypoxic rats.

The distribution and abundance of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers in four different regions of the laryngeal mucosa were compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In the chronically hypoxic laryngeal mucosa, the number of SP and CGRP fibers within and just beneath the epithelium, and around the laryngeal gland was increased in comparison with those in the normoxic controls. Especially in the epiglottic and arytenoid regions, the number of intraepithelial SP fibers was increased remarkably. Most intraepithelial SP and CGRP fibers penetrated into the epithelium to extend to the luminal surface. There was no distinct difference in the distribution and abundance of these peptidergic fibers in the mucosa of the normoxic and chronically hypoxic vocal cord regions. These results suggest that the increased density of SP and CGRP fibers within the epithelium of the upper laryngeal mucosa is a predominant feature of hypoxic adaptation, and this may be involved in airway protection, swallowing, and other functions in the chronically hypoxic environment. In addition, the increased SP and CGRP fibers around the laryngeal gland suggest an enhanced mucous secretion, and this may participate in the airway defense mechanism in low O2 conditions.

Animals↗
PubMed1999

[The benefit of head rotation on pharyngoesophageal dysphagia from three cases of paraganglioma in the parapharyngeal space].

The benefit of head rotation to the affected side is indicated during swallowing in patients complaining of dysphagia with unilateral pharyngeal palsy and/or laryngeal palsy. We experienced three cases of severe dysphagia after operations for giant paragangliomas (two vagal paraganglioma and one carotid body tumor) in the parapharyngeal space. During operation, the transmandibular transpterygoid approaches were applied to ensure better surgical views, and tracheostomy was performed to keep the airway open after operation. In each case, dysphagia during the pharyngeal stage of swallowing was significantly improved with rehabilitation using of this head rotation. We believe that rather than forbid oral intake, using an active bolus with head rotation is important for cases where dysphagia in the pharyngeal stage of swallowing is present with unilateral pharyngeal and/or laryngeal palsy. Repetitive swallowing exercises are important to reacquire the complicated movement of swallowing. Additionally, an active bolus flowing into the pyriform sinus on the healthy side will prevent a relaxation disorder of the cricopharyngeal muscle on that side. Furthermore, compensatory movement of the arytenoid on the healthy side improves dysphagia. We emphasize the usefulness of head rotation during swallowing rehabilitation for dysphagia with unilateral pharyngeal and/or laryngeal palsy in spite of its simplicity.

Aged↗
PubMed1999

[Development of treatments for head and neck squamous cell carcinomas].

Histopathologically, about 90% of head and neck carcinomas are squamous cell carcinomas. In this paper, the changes and the recent developments in treatment modalities for squamous cell carcinomas in the head and neck are reviewed. The curative treatments for head and neck carcinomas are radiation and/or surgical resection. The development of diagnostic techniques and the introduction of these curative treatments have contributed to an improvement in the long-term outcome. In terms of surgical procedures, reconstructive surgeries such as free cutaneous and/or muscle flap procedures have been developed and led to extended radical resection, while with curative radiotherapy, the increase in total dose and improvements in radiation field have been made possible. However, there has been a limit regarding significant improvements in prognosis with these curative therapies alone, excluding laryngeal cancer, because of the difficulty of early detection. Since the 1980 s, multi-drug chemotherapy including cisplatin (CDDP) has been administered in advanced cases. First, this chemotherapy was applied as neo-adjuvant chemotherapy (NAC) for previously untreated cases followed by curative surgery or radiotherapy. As a result, chemotherapy including CDDP and 5-fluorouracil has been shown to be the most efficacious with a high complete response (CR) rate. Furthermore, cases with CR have shown better outcomes than those without CR. Curative treatment modalities including impact chemotherapy have been invented and trials have begun with the aim of organ preservation. These include NAC followed by curative radiotherapy, curative radiotherapy with chemotherapy with almost the same anti-tumor effect as NAC and potential a radiation sensitizer (concomitant chemoradiotherapy), and NAC followed by concomitant chemoradiotherapy. These treatment modalities, including impact chemotherapy, are recommendable for the preservation of functions, e. g., swallowing and/or articulation, without worsening the prognosis. Furthermore, maintenance chemotherapy subsequent to curative treatment is advisable for advanced head and neck carcinomas. Besides the future development of the above-mentioned treatment modalities, new treatment modalities taking QOL into consideration for the elder are necessary, and improvements in poor prognoses of cases with complications and those with double cancer which are common in patients with head and neck squamous cell carcinomas is indispensable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Comparison in strategies for advanced head and neck squamous cell carcinomas between Japan and western countries].

The recent strategies for advanced head and neck squamous cell carcinoma (HNSCC) were reviewed and compared between Japan and western countries. The curative treatments for advanced HNSCC are radiotherapy and/or surgical resection. These standard treatment modalities are the same in both areas. However, combined treatment, especially including impact chemotherapy, was developed in western countries earlier than in Japan. The organ preservation modality to preserve the organ and physiological function has been under investigation in controlled randomized trials in western countries. Patients with advanced HNSCC, for example, achieving a complete response at the primary lesion after neo-adjuvant chemotherapy followed by curative radiotherapy or concomitant chemoradiotherapy including impact chemotherapy, receive organ-sparing treatment. This strategy for advanced HNSCC in Japan promises to be widespread in future.

Antineoplastic Combined Chemotherapy Protocols↗